<SEC-DOCUMENT>0000874015-23-000105.txt : 20230222
<SEC-HEADER>0000874015-23-000105.hdr.sgml : 20230222
<ACCEPTANCE-DATETIME>20230222163954
ACCESSION NUMBER:		0000874015-23-000105
CONFORMED SUBMISSION TYPE:	10-K
PUBLIC DOCUMENT COUNT:		123
CONFORMED PERIOD OF REPORT:	20221231
FILED AS OF DATE:		20230222
DATE AS OF CHANGE:		20230222

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			IONIS PHARMACEUTICALS INC
		CENTRAL INDEX KEY:			0000874015
		STANDARD INDUSTRIAL CLASSIFICATION:	PHARMACEUTICAL PREPARATIONS [2834]
		IRS NUMBER:				330336973
		STATE OF INCORPORATION:			CA
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		10-K
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		23653896

	BUSINESS ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		2855 GAZELLE COURT
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92010

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	ISIS PHARMACEUTICALS INC
		DATE OF NAME CHANGE:	19930328
</SEC-HEADER>
<DOCUMENT>
<TYPE>10-K
<SEQUENCE>1
<FILENAME>form10k.htm
<DESCRIPTION>IONIS PHARMACEUTICALS, INC. 10-K 12-31-2022
<TEXT>
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<div>UNITED STATES</div>
</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">SECURITIES AND EXCHANGE COMMISSION</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Washington, DC 20549</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 18pt; font-weight: bold;">FORM <ix:nonNumeric name="dei:DocumentType" id="Fact_e3ba0e166ef74614a026546e7499b9b3" contextRef="c20220101to20221231">10-K</ix:nonNumeric></div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934</div>
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the transition period from ___________ to ___________</div>

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  <div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Registrant&#8217;s telephone number, including area code)</div>

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  <div style="text-align: center; margin-top: 6pt; margin-bottom: 6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities registered pursuant to Section 12(b) of the Act:</div>

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    <td style="width: 1.39%; vertical-align: top;">&#160;</td>

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  <div style="text-align: left; text-indent: 18pt;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Securities registered pursuant to Section 12(g) of the Act: <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">None</span></div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

    <td style="width: 34.31%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>

    <td style="width: 32.84%; vertical-align: top;">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. <ix:nonNumeric name="dei:EntityWellKnownSeasonedIssuer" id="Fact_0f90345e809d4cf6b7f978d8fd9572a8" contextRef="c20220101to20221231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: justify;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check if the Registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;&#160; </span><ix:nonNumeric name="dei:EntityVoluntaryFilers" id="Fact_ee5c2b7c4e634588833109a1ffc14604" contextRef="c20220101to20221231">No</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the Registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934
    during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. <ix:nonNumeric name="dei:EntityCurrentReportingStatus" id="Fact_300b4d2330224213b076e9e6499b6626" contextRef="c20220101to20221231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: justify;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of
    Regulation S-T (&#167;232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). <ix:nonNumeric name="dei:EntityInteractiveDataCurrent" id="Fact_1b31a9bac81f4097918733e02b49c2a6" contextRef="c20220101to20221231">Yes</ix:nonNumeric>&#160;<span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;&#160; </span>No <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div style="text-align: left;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an
    emerging growth company. See the definitions of &#8220;large accelerated filer,&#8221; &#8220;accelerated filer,&#8221; &#8220;smaller reporting company,&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>

  <div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
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  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 48.93%; vertical-align: top;">
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    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
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  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-accelerated Filer <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>
        </td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Smaller Reporting Company <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntitySmallBusiness" id="Fact_91eeefab6682420999be40e6c31ac04b" contextRef="c20220101to20221231" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 48.93%; vertical-align: top;">&#160;</td>

    <td style="width: 2.14%; vertical-align: bottom;">&#160;</td>

    <td style="width: 48.93%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Emerging Growth Company <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityEmergingGrowthCompany" id="Fact_188764f752db41d092fb4059887164a6" contextRef="c20220101to20221231" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span></div>
        </td>

  </tr>


</table>
  <div style="text-align: center;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If an emerging growth company, indicate by check mark if the registrant has
      elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Securities Act. </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether the registrant has filed a report on and attestation to its management assessment of the effectiveness of its internal
    controls over financial reporting under Section 4049b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:IcfrAuditorAttestationFlag" id="Fact_174112ac8479469e887aa32671b97e52" contextRef="c20220101to20221231" format="ixt-sec:boolballotbox">&#x2612;</ix:nonNumeric></span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the
    filing reflect the correction of an error to previously issued financial statements.&#160; <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by
    any of the registrant&#8217;s executive officers during the relevant recovery period pursuant to &#167;240.10D-1(b).&#160; <span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9744;</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Indicate by check mark whether the Registrant is a shell company (as defined in
      Rule 12b-2 of the Act). Yes </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';"><ix:nonNumeric name="dei:EntityShellCompany" id="Fact_08e1194fee4d4dc78013dd754e31c40a" contextRef="c20220101to20221231" format="ixt-sec:boolballotbox">&#x2610;</ix:nonNumeric></span><span style="font-size: 12pt; font-family: 'Segoe UI Symbol';">&#160; </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">No </span><span style="font-size: 10pt; font-family: 'Segoe UI Symbol';">&#9746;</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approximate aggregate market value of the voting common stock held by non-affiliates of the Registrant, based upon the last sale price of the common
    stock reported on The Nasdaq Global Select Market was $<ix:nonFraction name="dei:EntityPublicFloat" id="Fact_ab9111deb9864fcebfc9651f4c6eaec2" contextRef="c20220630" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">3,804,704,734</ix:nonFraction> as of June 30, 2022.*</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The number of shares of voting common stock outstanding as of February 16, 2023 was <ix:nonFraction name="dei:EntityCommonStockSharesOutstanding" id="Fact_29353a629ff649f28f9d8a2c5665c7bb" contextRef="c20230216" unitRef="U002" decimals="INF" scale="0" format="ixt:num-dot-decimal">142,953,993</ix:nonFraction>.</div>

  <div><br />
  </div>

  <div style="text-align: center; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">DOCUMENTS INCORPORATED BY REFERENCE</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Portions of the Registrant&#8217;s definitive Proxy Statement to be filed on or about April 20, 2023 with the Securities and Exchange Commission in connection with
    the Registrant&#8217;s annual meeting of stockholders to be held on June 1, 2023 are incorporated by reference into Part III of this Report.</div>

  <div style="text-align: left; text-indent: 18pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 30.71%; vertical-align: top; border-bottom: #000000 2px solid;">&#160;</td>

    <td style="width: 69.29%; vertical-align: top;">&#160;</td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Excludes 39,056,355 shares of common stock held by directors and officers and by stockholders whose beneficial ownership is known by the Registrant to exceed 10 percent
            of the common stock outstanding at June 30, 2022. Exclusion of shares held by any person should not be construed to indicate that such
            person possesses the power, direct or indirect, to direct or cause the direction of the management or policies of the Registrant, or that such person is controlled by or under common control with the Registrant.</div>
        </td>

  </tr>


</table>
  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;">
    <hr style="border: none; border-bottom: 4px solid black; border-top: 1px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;" /></div>

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    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

  </div>

  <div class="BRPFPageHeader"></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORWARD-LOOKING STATEMENTS</div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><!--PROfilePageNumberReset%Num%2%%%--></div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">This report on Form 10-K and the information incorporated herein by reference includes forward-looking statements
    regarding our business and the therapeutic and commercial potential of SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen), eplontersen, olezarsen, donidalorsen, ION363, tofersen, pelacarsen, bepirovirsen and our technologies and
    products in development. Any statement describing our goals, expectations, financial or other projections, intentions or beliefs, is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks
    and uncertainties and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Our
    forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Factors that could cause or
    contribute to such differences include, but are not limited to, those discussed in this report on Form 10-K, including those identified in Item 1A entitled &#8220;Risk Factors&#8221;. Although our forward-looking statements reflect the good faith judgment of our
    management, these statements are based only on facts and factors currently known by us. As a result, you are cautioned not to rely on these forward-looking statements.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In this report, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals, Inc. and
    its subsidiaries.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Summary of Risk Factors</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of risks related to our business and our securities. Below is a summary of material factors that make an investment in
    our securities speculative or risky. Importantly, this summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, as well as other risks that we face, can be found in this report
    on Form 10-K in Item 1A entitled &#8220;Risk Factors&#8221;:</div>

  <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#927;</span>ur ability to generate substantial revenue from the sale of our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The availability of adequate coverage and payment rates for our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our and our partners&#8217; ability to compete effectively;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to successfully manufacture our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to successfully develop and obtain marketing approvals for our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to secure and maintain effective corporate partnerships;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to sustain cash flows and achieve consistent profitability;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to protect our intellectual property;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our ability to maintain the effectiveness of our personnel; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The impacts of the COVID-19 pandemic.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">TRADEMARKS</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>&#8220;Ionis,&#8221; the Ionis logo, and other
    trademarks or service marks of Ionis Pharmaceuticals, Inc. appearing in this report are the property of Ionis Pharmaceuticals, Inc. &#8220;Akcea,&#8221; the Akcea logo, and other trademarks or service marks of Akcea Therapeutics, Inc. appearing in this report are
    the property of Akcea Therapeutics, Inc., Ionis&#8217; wholly owned subsidiary. This report contains additional trade names, trademarks and service marks of others, which are the property of their respective owners. Solely for convenience, trademarks and
    trade names referred to in this report may appear without the &#174; or TM symbols.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CORPORATE INFORMATION</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California in 1989 and in January 1991 we changed our state of incorporation to Delaware. In December 2015, we changed
    our name to Ionis Pharmaceuticals, Inc. from Isis Pharmaceuticals, Inc. Our principal offices are in Carlsbad, California. In December 2014, we formed Akcea Therapeutics, Inc., as a Delaware corporation, with its principal office in Boston,
    Massachusetts. Prior to Akcea&#8217;s initial public offering, or IPO, in July 2017, we owned 100 percent of Akcea&#8217;s stock. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We make available, free of charge, on our website, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">www.ionispharma.com</span>, our reports on Forms 10-K, 10-Q, 8-K and amendments thereto, as soon as reasonably practical after we file such materials with the Securities and Exchange Commission, or SEC. Periodically, we provide
    updates about the company in the Newsroom section of the Investors &amp; Media page of our website. Any information that we include on or link to our website is not a part of this report or any registration statement that incorporates this report by
    reference. The SEC maintains an internet site, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">www.sec.gov</span>, that contains reports, proxy and information statements that we file electronically
    with the SEC.</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="TOC"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">FORM 10-K</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">For the Fiscal Year Ended December 31, 2022</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Table of Contents</div>

  <div><br />
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#PARTI"><span style="text-decoration: underline;">PART I</span></a></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Page</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1.</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item1">Business</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1A.</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item1A">Risk Factors</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">43</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1B.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item1B">Unresolved Staff Comments</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 2.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item2">Properties</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 3.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item3">Legal Proceedings</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 4.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item4">Mine Safety Disclosures</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#PARTII">PART II</a></div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 5.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item5">Market for Registrant&#8217;s Common Equity, Related Stockholder
              Matters and Issuer Purchases of Equity Securities</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 6.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item6">Selected Financial Data</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 7.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item7">Management&#8217;s Discussion and Analysis of Financial Condition and
              Results of Operations</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 7A.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item7A">Quantitative and Qualitative Disclosures About Market Risk</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 8.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item8">Financial Statements and Supplementary Data</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
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    <td style="width: 10.51%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item9">Changes in and Disagreements With Accountants on Accounting and
              Financial Disclosure</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9A.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item9A">Controls and Procedures</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">71</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9B.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item9B">Other Information</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 9C.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item9C">Disclosure Regarding Foreign Jurisdictions that Prevent
              Inspections</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#PARTIII">PART III</a></div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 10.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item10">Directors, Executive Officers and Corporate Governance</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 11.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item11">Executive Compensation</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 12.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item12">Security Ownership of Certain Beneficial Owners and Management
              and Related Stockholder Matters</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 13.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item13">Certain Relationships and Related Transactions, and Director
              Independence</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 14.</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item14">Principal Accountant Fees and Services</a></div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#PARTIV">PART IV</a></div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 6.27%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 15.</div>
        </td>

    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Item15">Exhibits, Financial Statement Schedules</a></div>
        </td>

    <td style="width: 6.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
        </td>

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    <td style="width: 83.22%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Signatures">Signatures</a></div>
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    <td style="width: 83.22%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82</div>
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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTI"><!--Anchor--></a>PART I</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1"><!--Anchor--></a>Item 1. Business</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Overview</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We were founded over 30 years ago to deliver innovative medicines for diseases with great medical need. Today, we are building on our
    advancements in RNA-targeted therapeutics to move us closer to achieving our vision to be the leader in genetic medicines. We believe our medicines have the potential to pioneer new markets, change standards of care and transform the lives of people
    with devastating diseases.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have three marketed medicines: SPINRAZA, TEGSEDI and WAYLIVRA. Additionally, we have two medicines that will add to our
    commercial portfolio this year, assuming positive regulatory outcomes. These medicines are eplontersen to treat patients with polyneuropathy caused by hereditary transthyretin amyloidosis, or ATTRv-PN, and tofersen to treat patients with superoxide
    dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. We submitted the eplontersen New Drug Application, or NDA, to the U.S. Food and Drug Administration, or FDA, in December 2022. Tofersen is currently under regulatory review in the United States,
    or U.S., and European Union, or EU. In the U.S., tofersen has a Prescription Drug User Fee Act, or PDUFA, date of April 25, 2023. We also have a rich innovative late- and mid-stage pipeline primarily focused on our leading cardiovascular and neurology
    franchises. We currently have seven medicines in Phase 3 development. Additionally, based on recent positive data from the Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with immunoglobulin A nephropathy, or IgAN, Roche plans to advance
    IONIS-FB-L<sub>Rx</sub> into Phase 3 development, which would further expand our late-stage pipeline.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the past year, we made important progress advancing our strategic priorities: to deliver an abundance of new medicines to the market,
    establish an integrated commercial organization and expand and diversify our technology platform. Last year, we delivered nine positive data readouts from our mid- and late-stage pipeline, positioning us to add to our commercial portfolio and our
    late-stage pipeline. We advanced our go-to-market plans for our near-term commercial opportunities, eplontersen, olezarsen and donidalorsen. We also expanded and diversified our technology when we advanced new medicines targeting muscle and using our
    MsPA backbone into preclinical development. Additionally, in late 2022, we entered into a collaboration with Metagenomi to add next generation gene editing capabilities to our technologies.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We accomplished all of this while earning revenues of $587 million for 2022 and ending the year with a cash and short-term investment
    balance of $2.0 billion. We strengthened our balance sheet with our recent sale and leaseback and royalty monetization transactions in late 2022 and January 2023, respectively. Under the sale and leaseback transaction, we received net proceeds of
    approximately $200 million, with the potential to receive additional payments of up to $40 million plus funding to expand our research and development, or R&amp;D campus. Under our agreement with Royalty Pharma Investments, or Royalty Pharma, we
    received an upfront payment of $500 million in January 2023 when Royalty Pharma acquired a minority interest in our future SPINRAZA and pelacarsen royalties. Additionally, we have the potential to earn up to $625 million in pelacarsen milestone
    payments from Royalty Pharma.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our multiple sources of revenue and strong balance sheet enable us to continue investing in our commercial readiness efforts for multiple
    late-stage programs and our innovative pipeline. By continuing to focus on these priorities, we believe we are well positioned to drive future growth and to deliver increasing value for patients and shareholders.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Marketed Medicines</div>

  <div><br />
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA is the global market leader for the treatment of patients with spinal muscular atrophy, or SMA, a progressive, debilitating and
      often fatal genetic disease. Biogen is our partner responsible for commercializing SPINRAZA worldwide. From inception through December 31, 2022, we have earned more than $1.8 billion in revenues from our SPINRAZA collaboration, including more than
      $1.4 billion in royalties on sales of SPINRAZA.</div>

  </div>

  <div>
    <div><br />
    </div>

  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is a once weekly, self-administered subcutaneous medicine approved in the U.S., Europe, Canada and Brazil for the treatment of
      patients with ATTRv-PN. We launched TEGSEDI in the U.S. and the EU, in late 2018. In 2021, we began selling TEGSEDI in Europe through our distribution agreement with Swedish Orphan Biovitrum AB, or Sobi, and in the second quarter of 2021, Sobi began
      distributing TEGSEDI in the U.S. and Canada. In Latin America, PTC Therapeutics International Limited, or PTC, is commercializing TEGSEDI in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement
      with us.</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA is a once weekly, self-administered, subcutaneous medicine that received conditional marketing authorization in May 2019 from
      the European Commission, or EC, as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome, or FCS, and at high risk for pancreatitis. We launched WAYLIVRA in the EU in the third quarter of 2019. In 2021, we
      began selling WAYLIVRA in Europe through our distribution agreement with Sobi. In Latin America, PTC is commercializing WAYLIVRA in Brazil for two indications, FCS and familial partial lipodystrophy, or FPL, and is pursuing access in additional Latin
      American countries through its exclusive license agreement with us.</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Medicines in Phase 3 Studies and Registration</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have seven medicines in Phase 3 studies for nine indications, which are:</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen: our medicine in development for transthyretin amyloidosis, or ATTR</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN, the Phase 3 CARDIO-TTRansform study in patients with ATTR cardiomyopathy, or
            ATTR-CM, and additional studies supporting our ATTR development program</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2022, we submitted the NDA for eplontersen in the U.S. for patients with ATTRv-PN based on the<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> positive results from an interim analysis of the Phase 3 NEURO-TTRansform study of eplontersen in patients with ATTRv-PN we first reported in June 2022</span></div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen: our medicine in development for FCS and severe hypertriglyceridemia, or SHTG</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a broad Phase 3 development program for olezarsen that includes the Phase 3 BALANCE study in patients with FCS and three Phase 3 studies
            supporting development for the treatment of SHTG: CORE, CORE2 and ESSENCE</div>
        </td>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e achieved full enrollment in the BALANCE Phase 3 study in patients with FCS
              with data&#160; expected in the second half of 2023</span></div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the second half of 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e expanded our Phase 3 program for SHTG when we initiated CORE2,
              a confirmatory Phase 3 study of olezarsen in patients with SHTG and ESSENCE, a supporting Phase 3 study of olezarsen in patients with SHTG or hypertriglyceridemia and atherosclerotic cardiovascular disease</span></div>
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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA granted olezarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> fast track designation for the treatment of patients with FCS</span></div>
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    <td style="width: 22.5pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen: our medicine in development for hereditary angioedema, or HAE</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting the Phase 3 OASIS-HAE study in patients with HAE and the Phase 3 OASIS-Plus supportive study for HAE patients previously treated with other
            prophylactic therapies</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reported positive data from the Phase 2 study and Phase 2 open-label extension, or OLE, study throughout 2022 and early 2023</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION363: our medicine in development for amyotrophic lateral sclerosis, or ALS, with mutations in the fused in sarcoma gene, or <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">FUS</span></div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a Phase 3 study of ION363 in juvenile and adult patients with FUS-ALS</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen: our medicine in development for SOD1-ALS</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is developing tofersen, including conducting the ongoing Phase 3 VALOR OLE study in patients with SOD1-ALS and the ongoing Phase 3 ATLAS study in presymptomatic
            SOD1 patients</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen is currently under regulatory review in the U.S. with a PDUFA date of April 25, 2023 and in the EU</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, Biogen presented new positive data from the ongoing VALOR OLE study at the European Network to Cure ALS, or ENCALS, meeting. These data were included in the
            NDA filing and Marketing Authorization Application, or MAA, filing</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pelacarsen: our medicine in development to treat patients with elevated lipoprotein(a), or Lp(a) and cardiovascular disease</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis is developing pelacarsen, including conducting the ongoing Lp(a) HORIZON Phase 3 cardiovascular outcome study in patients with established cardiovascular disease
            and elevated Lp(a)</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2022, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Novartis achieved full enrollment in the Lp(a) HORIZON study</span></div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Bepirovirsen: our medicine in development for chronic hepatitis B virus, or HBV</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">o</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GSK is developing bepirovirsen, including conducting the ongoing B-Well Phase 3 program in patients with HBV</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, GSK presented positive data from the Phase 2b B-Clear study of bepirovirsen demonstrating potential for functional cures in patients with chronic HBV</div>
        </td>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">COVID-19</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As a company focused on improving the health of people around the world, our priority during the COVID-19 pandemic has been the
      safety of our employees, their families, the healthcare workers who work with us and the patients who rely on our medicines. We have also been focused on maintaining the quality of our studies and minimizing the impact to timelines. While the
      COVID-19 pandemic has impacted some areas of our business, we believe our mitigation efforts and financial strength have enabled us to continue to manage through the pandemic and execute on our strategic initiatives. Because the situation is fluid,
      we continue to monitor the impact COVID-19 could have on our business, including the impact on our commercial products and the medicines in our pipeline.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Marketed Medicines &#8211; Potentially Transformational Medicines Bringing Value to Patients Today</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">SPINRAZA </span>&#8211; SPINRAZA (nusinersen)
    injection for intrathecal use is a survival motor neuron-2, or SMN2, directed antisense medicine indicated for the treatment of <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">spinal muscular atrophy, or SMA, </span>in
    pediatric and adult patients.</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">SPINRAZA is the global market leader for the treatment of
      patients with </span>SMA, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a progressive, debilitating and often fatal genetic disease. Our partner, Biogen, is responsible for commercializing SPINRAZA worldwide.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SMA is characterized by loss of motor neu<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">rons in the spinal
      cord and lower brain stem. People with SMA have a deletion or defect in their </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene and rely on their </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene to
      produce functional SMN protein, which motor neurons need to maintain motor function and muscle strength. However, the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SMN2</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene can only produce approximately 10 percent of the SMN protein critical for motor neurons, resulting in severe and progressive loss of motor function and strength.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The rate and severity of degeneration varies depending on the amount of functional SMN protein a patient can produce. Type 1, or
    infantile-onset, SMA is the most severe form of the disease. Type 1 SMA patients produce very little SMN protein and often progress to death or permanent ventilation by the age of 2. Patients with Type 2 or Type 3, or later-onset, SMA produce more SMN
    protein, but also suffer from a progressive loss of muscle strength and function and a reduced life expectancy.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen continues to expand the body of evidence supporting SPINRAZA&#8217;s durable efficacy and well-established safety profile to address
    the remaining needs of SMA patients of all ages. This includes the following ongoing studies:</div>

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            <div style="text-align: left; margin-left: 22.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">DEVOTE: In the Phase 2/3 DEVOTE study, Biogen is evaluating the safety and potential to achieve increased efficacy with a higher dose of SPINRAZA
              compared to the currently approved dose. In 2022, Biogen reported final data from Part A of the ongoing, three-part DEVOTE study. Results from Part A, an open-label safety evaluation period in children and teens with later-onset SMA, suggest
              that the higher dosing regimen of SPINRAZA leads to higher levels of the drug in the cerebrospinal fluid, supporting further development of a higher dose of SPINRAZA. Additionally, the results indicated that SPINRAZA was generally
              well-tolerated.</div>
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            <div style="text-align: left; margin-left: 22.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RESPOND: In the Phase 4 RESPOND study, Biogen is evaluating the benefit of SPINRAZA in infants and children with a suboptimal clinical response to
              the gene therapy, onasemnogene abeparvovec. In 2022, Biogen reported that increasing enrollment in the RESPOND study indicates there are residual unmet clinical needs in infants and toddlers with SMA who have unmet needs following gene
              therapy treatment.</div>
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            <div style="text-align: left; margin-left: 22.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8226;</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ASCEND: In the Phase 3b ASCEND study, Biogen is evaluating the clinical outcomes and assessing the safety of a higher dose of SPINRAZA in children,
              teens and adults with later-onset SMA following treatment of risdiplam. The first patient was treated in the ASCEND study in the first quarter of 2022.</div>
          </td>

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  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, Biogen continues to conduct the Phase 2 NURTURE study, an open-label study investigating the benefit of SPINRAZA when
    administered before symptom onset in patients genetically diagnosed with SMA, and likely to develop Type 1 or Type 2 SMA. NURTURE was the first study to investigate the potential to slow or stop SMA disease progression in presymptomatic SMA patients.
    In 2022, Biogen reported new NURTURE study data, showing that early and sustained treatment with SPINRAZA helped participants to maintain and/or make progressive gains in motor function. These data showed that after 11 months of additional follow-up
    since the 2020 interim analysis, all children who were able to walk alone maintained this ability and one child gained the ability to walk alone, increasing the total percentage of study participants able to walk from 92% to 96%. Further, most children
    achieved motor milestones within age-appropriate timelines and no major motor milestones were lost. The safety of SPINRAZA over this extended follow-up period was consistent with previously reported findings.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approval of SPINRAZA was based on efficacy and safety data from multiple clinical studies, including two randomized,
    placebo-controlled Phase 3 studies, ENDEAR, in patients with infantile-onset SMA, and CHERISH, in patients with later-onset SMA as well as from SHINE, an open-label extension, or OLE, study for patients with SMA who participated in prior SPINRAZA
    studies.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">TEGSEDI &#8211; </span>TEGSEDI (inotersen)
    injection is an antisense medicine indicated for the treatment of ATTRv-PN in adults. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">TEGSEDI prevents the production of TTR protein, reducing the amount of amyloid buildup
      that damages organs and tissues.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ATTRv-PN</span> is caused by the accumulation of misfolded
    mutated TTR protein in the peripheral nerves. Patients with ATTRv-PN experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other
    major organs, which progressively compromises their function and eventually leads to death within five to fifteen years of disease onset. There are an estimated 40,000 addressable patients, which includes those with ATTRv-PN and those with ATTRv-mixed
    phenotype worldwide.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI is commercially available in numerous countries, including the U.S., many European countries, Canada, and Latin America. We
    launched TEGSEDI in the U.S. and EU in late 2018. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021, we began selling TEGSEDI in the U.S., Canada and Europe through our distribution agreement with Sobi. In Latin
      America, PTC is commercializing TEGSEDI in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement with us.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The approvals of TEGSEDI were based on efficacy and safety data from the Phase 3 NEURO-TTR study in patients with ATTRv-PN.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">WAYLIVRA &#8211; </span>WAYLIVRA (volanesorsen)
    is an antisense medicine indicated as an adjunct to diet in adult patients with genetically confirmed FCS and at high risk for acute, potentially fatal pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">WAYLIVRA reduces triglyceride levels by inhibiting the production of apolipoprotein C-III, or ApoC-III, a protein that is a key regulator of triglyceride levels.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FCS is a rare, genetic disease estimated to affect one to two individuals per million and characterized by extremely elevated
    triglyceride levels, typically greater than 1,000 mg/dl. FCS can lead to many chronic health issues including severe, recurrent abdominal pain, fatigue, high risk of life-threatening pancreatitis and abnormal enlargement of the liver or spleen. In
    addition, people with FCS are often unable to work, adding to their disease burden. In severe cases, patients can have bleeding into the pancreas, serious tissue damage, infection, and cyst formation, as well as damage to other vital organs such as the
    heart, lungs, and kidneys.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA received conditional marketing authorization in May 2019 from the European Commission, or EC. WAYLIVRA is commercially available
    in multiple European countries and in Latin America. We launched WAYLIVRA in the EU in the third quarter of 2019. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021, we began selling WAYLIVRA in Europe through our
      distribution agreement with Sobi. In Latin America, WAYLIVRA is approved for two indications, FCS and FPL. PTC is commercializing WAYLIVRA in Brazil and is pursuing access in additional Latin American countries through its exclusive license agreement
      with us. In the fourth quarter of 2022, WAYLIVRA was approved in Brazil for a second indication, FPL.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">WAYLIVRA&#8217;s conditional marketing authorization in the EU for FCS and approval in Brazil for FCS we<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">re based </span>on efficacy and safety data from <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the Phase 3 APPROACH study and
      supported by results from the Phase 3 COMPASS study.</span> WAYLIVRA&#8217;s approval in Brazil for FPL was<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> based </span>on efficacy and safety data
    from <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the Phase 3 BROADEN study in patients with FPL.</span></div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Innovative Pipeline of Genetic Medicines</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Today, we are a leader in the discovery and development of RNA-targeted therapeutics. We are focused on pioneering new markets and
    changing standards of care with a focus on cardiovascular and neurological diseases. We also have an emerging specialty rare disease pipeline comprised of medicines that we believe represent compelling opportunities for us. We are building on our
    capabilities in RNA-targeted therapeutics to achieve our vision to be the leader in genetic medicines.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The table below lists the medicines in our clinical pipeline. We categorize patient studies to establish a medicine&#8217;s safety profile as
    Phase 1/2 and those studies in healthy volunteers as Phase 1. The table includes the disease indication, the partner (if the medicine is partnered), and the development status of each medicine. We have included descriptions for each of our medicines in
    Phase 2 and Phase 3 development below.</div>

  <div><br />
  </div>

  <div style="text-align: center;"><img width="717" height="341" src="image0.jpg" alt="graphic" /></div>

  <div><br />
  </div>

  <div style="text-align: center;"><img width="713" height="80" src="image1.jpg" alt="graphic" /></div>

  <div><br />
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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Late-Stage Pipeline</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently have seven medicines in our late-stage pipeline: eplontersen, olezarsen, donidalorsen, ION363, tofersen, pelacarsen and
    bepirovirsen.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;<img width="714" height="313" src="image2.jpg" alt="graphic" /></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Eplontersen (TTR) &#8211; Eplontersen (TTR) &#8211; </span>Eplontersen
    (formerly<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-TTR-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">) is an investigational LIgand-Conjugated Antisense, or LICA, medicine we designed </span>to inhibit the production of TTR protein. We are developing eplontersen as a monthly self-administered
    subcutaneous injection to treat all types of ATTR. ATTR amyloidosis is a systemic, progressive and fatal disease in which patients experience multiple overlapping clinical manifestations caused by the inappropriate formation and aggregation of TTR
    amyloid deposits in various tissues and organs, including peripheral nerves, heart, intestinal tract, eyes, kidneys, central nervous system, thyroid and bone marrow. The progressive accumulation of TTR amyloid deposits in these tissues and organs leads
    to organ failure and eventually death.</div>

  <div>
    <div><br />
    </div>

    <div style="text-align: justify; text-indent: 36pt; margin-top: 11.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ATTRv-PN is caused by the accumulation of misfolded mutated TTR protein in the peripheral nerves. Patients with
      ATTRv-PN experience ongoing debilitating nerve damage throughout their body resulting in the progressive loss of motor functions, such as walking. These patients also accumulate TTR in other major organs, which progressively compromises their
      function and eventually leads to death within five to fifteen years of disease onset. There are an estimated 40,000 addressable patients, which includes those&#160; with ATTRv-PN and those with ATTRv- mixed phenotype worldwide.</div>

    <div style="text-align: justify; text-indent: 36pt; margin-top: 11.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ATTR-CM is caused by the accumulation of misfolded TTR protein in the cardiac muscle. Patients experience ongoing
      debilitating heart damage resulting in progressive heart failure, which results in death within three to five years from disease onset. ATTR-CM includes both the genetic and wild-type form of the disease. There are an estimated 300,000 to 500,000
      patients with ATTR-CM worldwide.</div>

    <div style="text-align: justify; text-indent: 36pt; margin-top: 11.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Often, patients with ATTRv-PN will have TTR build up in the heart and experience cardiomyopathy symptoms.
      Similarly, patients with ATTR-CM may often have TTR build up in their peripheral nerves and experience nerve damage and progressive difficulty with motor functions.</div>

    <div style="text-align: justify; text-indent: 36pt; margin-top: 11.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2022, we submitted the eplontersen NDA to the FDA for patients with ATTRv-PN. The eplontersen NDA
      included results from the interim analysis of the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN. NEURO-TTRansform is <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a global, multi-center, randomized,
        open-label study designed to evaluate the efficacy, safety and tolerability of eplontersen. The current study compares to the historical placebo arm from the TEGSEDI (inotersen) NEURO-TTR Phase 3 study. In June 2022, we reported positive interim
        analysis data from the</span> NEURO-TTRansform study. In the interim analysis, eplontersen demonstrated a statistically significant and clinically meaningful change from baseline for the co-primary and secondary endpoints at 35 weeks compared to
      the external placebo group. In the study, eplontersen achieved an 81.2% (p&lt;0.0001) mean reduction in the co-primary endpoint of serum TTR concentration compared to baseline, demonstrating reduced TTR protein production. Eplontersen also
      demonstrated a significant treatment effect on the co-primary endpoint of modified Neuropathy Impairment Score +7, or mNIS+7, a measure of neuropathic disease progression, with a statistically significant difference in mean change from baseline
      versus the external placebo group (p&lt;0.0001). The study also met its key secondary endpoint of change from baseline in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy, or Norfolk QoL-DN, showing that treatment with eplontersen
      significantly improved patient-reported quality of life compared to the external placebo group (p&lt;0.0001). Eplontersen had a favorable safety and tolerability profile supportive of continued development.</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2020, we initiated the CARDIO-TTRansform Phase 3 cardiovascular outcome study of eplontersen in patients with ATTR-CM.
    CARDIO-TTRansform i<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">s </span>a global, multi-center, randomized, double-blind, placebo-controlled study in approximately 1,400 patients with ATTR-CM. We designed the study to
    evaluate the efficacy, safety and tolerability of eplontersen in patients with ATTR-CM. The CARDIO-TTRansform study includes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> co-</span>primary outcome measures of
    cardiovascular death and frequency of cardiovascular clinical events.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, the FDA granted an Orphan Medicine Designation for eplontersen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into an agreement with AstraZeneca to jointly develop and commercialize eplontersen in the U.S. We granted
    AstraZeneca exclusive rights to commercialize eplontersen outside the U.S, except for certain Latin American countries.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Olezarsen (ApoC-III)</span><sub style="font-weight: bold;">&#160;</sub><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>Olezarsen (formerly IONIS-APOCIII-L<sub>Rx</sub>) is an investigational LICA medicine we designed to inhibit
    the production of apoC-III for patients who are at risk of disease due to elevated triglyceride levels. ApoC-III is a protein produced in the liver that regulates triglyceride metabolism in the blood. People with severely elevated triglycerides, such
    as people with FCS, are at high risk for acute pancreatitis and an increased risk of cardiovascular disease, or CVD. It is estimated that FCS affects one to two individuals per million worldwide and more than three million patients have SHTG in the
    U.S.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are currently conducting a broad development program for olezarsen that includes the Phase 3 BALANCE study in patients with FCS
      and three Phase 3 studies supporting development for the treatment of SHTG: CORE, CORE2 and ESSENCE.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BALANCE is a global, multi-center, randomized, double-blind, placebo-controlled study in approximately 65 patients designed to assess
    the efficacy, safety and tolerability of olezarsen in patients with FCS. Patients will be treated with 50 mg or 80 mg of olezarsen monthly by subcutaneous injection. The primary endpoint is the percent change from baseline in fasting triglyceride
    levels at six months compared to placebo.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CORE and CORE2 are global, multi-center, randomized, double-blind, placebo-controlled studies enrolling approximately 540 and 390
    patients, respectively, designed to assess the efficacy, safety and tolerability of olezarsen in patients with SHTG. The CORE and CORE2 studies compare olezarsen to placebo in patients with triglyceride levels equal to or greater than 500 mg/dL who are
    on currently available therapies for elevated triglycerides. The primary endpoint of the studies is the percent change in fasting triglycerides from baseline at month six. Additionally, in November 2022, we initiated ESSENCE, a global, multi-center,
    randomized, double-blind, placebo-controlled study enrolling approximately 1,300 patients to provide a robust safety database. The primary endpoint of the study is the percent change in fasting triglycerides from baseline at week six.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2020, we reported positive results from a Phase
      2 clinical study in patients</span> with hypertriglyceridemia and at high risk of or with established CVD. Olezarsen achieved statistically significant, dose-dependent reductions in fasting triglycerides compared to placebo at all dose levels.
    Additionally, at the highest monthly dose, 91 percent of patients achieved serum triglycerides of &#8804; 150 mg/dL, the recognized threshold for cardiovascular risk, compared to less than five percent of patients in the placebo group. Olezarsen also
    achieved statistical significance in numerous key secondary endpoints, including significant reductions in apoC-III, very low-density lipoprotein cholesterol, or VLDL-C, and remnant cholesterol, and a statistically significant increase in high-density
    lipoprotein cholesterol, or HDL-C. Olezarsen had a favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, the FDA granted olezarsen fast track designation for the treatment of patients with FCS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Donidalorsen (PKK)</span>&#160;<span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211; </span>Donidalorsen (formerly IONIS-PKK-L<sub>Rx</sub>) is an investigational LICA medicine we designed to target the prekallikrein, or PKK, pathway. HAE is
    a rare genetic disease that is characterized by severe and potentially fatal swelling of the arms, legs, face and throat. PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. By inhibiting the
    production of PKK, donidalorsen could be an effective prophylactic approach to preventing HAE attacks. It is estimated that there are more than 20,000 patients with HAE in the U.S. and Europe.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2021, we initiated the Phase 3 study of donidalorsen, OASIS-HAE, in patients with HAE. OASIS-HAE is a multi-center,
    randomized, double-blind placebo-controlled study in approximately 80 patients designed to assess the efficacy, safety and tolerability of donidalorsen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patients will be
      treated with </span>an 80 mg dose of donidalorsen either every four weeks or every eight weeks by subcutaneous injection. The primary endpoint is the time-normalized number of investigator-confirmed HAE attacks per month from week one to week 25. In
    May 2022, we initiated OASIS-Plus, a multi-center, open-label, global study in approximately 110 patients who were either previously treated with other prophylactic therapies or who have completed OASIS-HAE.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In 2021 and 2022, we reported positive results from a Phase
      2 clinical study of donidalorsen in patients with HAE. Patients received either donidalorsen 80 mg or placebo subcutaneously once monthly for 17 weeks. The Phase 2 study met its primary and secondary endpoints, achieving significant reductions in the
      number of attacks suffered by patients with HAE compared to placebo. The study demonstrated a mean reduction of 90 percent in the number of monthly HAE attacks in weeks one to 17 of the study (p &lt;0.001) and a mean reduction of 97 percent in the
      number of monthly HAE attacks in weeks five to 17 (p=0.003). In weeks five to 17, 92 percent of patients treated with donidalorsen were attack-free compared to 0 percent in the placebo group (p &lt;0.001). Additionally, donidalorsen demonstrated an
      overall reduction in moderate to severe attacks starting with the second dose in the study. For the final month of the study, all donidalorsen treated patients were attack-free. Further, patients reported higher overall health-related quality of
      life, or HRQoL, over 17 weeks with donidalorsen, with a mean change in total score of the AE-QoL of -26.85, compared with -6.15 in the placebo group (P=0.002) where reduction in the score indicates better quality of life. There were improvements
      observed across all individual domains of the AE-QoL compared with placebo we published. The Phase 3 data were published in the New England Journal of Medicine. Donidalorsen had a favorable safety and tolerability profile supportive of continued
      development</span>.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022 and in early 2023, we reported positive results from the Phase 2 OLE study of donidalorsen in patients with HAE. Interim data
    after all patients completed one year of treatment in the study showed a sustained reduction in HAE attacks. Patients completing the Phase 2 study were eligible for enrollment in the OLE study. There were 20 Type 1 or Type 2 HAE patients in the Phase 2
    study, and 17 (85%) entered the OLE. Following a 13-week fixed-dose period where participants received subcutaneous donidalorsen 80 mg every four weeks, eight patients switched to subcutaneous donidalorsen 80 mg every eight weeks. Patients receiving
    donidalorsen 80 mg every eight weeks experienced a mean reduction in attack rate of 75.6% from baseline and the mean monthly attack rate was 0.28. Six of these patients remained attack free over the one year duration of this analysis, and two of these
    patients returned to 80 mg every four weeks. For patients treated with donidalorsen, 99.6% of study days were HAE attack-free. Additionally, patients treated for one year with donidalorsen reported a mean improvement of 24 points in their AE-QoL total
    score across all domains relative to baseline. Donidalorsen had a favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION363 (FUS)</span> &#8211; ION363 is an
    investigational antisense medicine we designed to reduce the production of the FUS protein to treat people with ALS caused by mutations in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">FUS</span>
    gene. Because antisense-mediated reduction of mutant FUS protein in a FUS-ALS mouse model demonstrated the ability to prevent motor neuron loss, it is hypothesized that reduction of FUS protein will reverse or prevent disease progression in FUS-ALS
    patients. It is estimated that there are approximately 350 patients with FUS-ALS in G7 countries (comprised of Canada, France, Germany, Italy, Japan, the United Kingdom and the U.S.).</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we initiated a Phase 3 study of ION363 in patients with FUS-ALS. The Phase 3 trial of ION363 is a global, multi-center,
    randomized, double-blind, placebo-controlled study in approximately 75 patients designed to assess the efficacy, safety and tolerability of ION363. Part 1 of the trial consists of patients randomized to receive a loading regimen of ION363 or placebo
    for weeks one and four followed by one dose every four to 12 weeks for 61 weeks, followed by Part 2, which will be an open-label period in which all patients in the trial will receive ION363 or placebo loading regimen at week four followed by one dose
    every 12 weeks for 85 weeks. The primary endpoint is the change from baseline as measured by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, or ALSFRS-R, Total Score, time of rescue or discontinuation from Part 1 and entering Part 2
    due to a deterioration in function, and Ventilation Assistance-free survival, or VAFS.</div>

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    <div style="text-align: justify; text-indent: 36pt; margin-top: 11.25pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Tofersen (SOD1) </span>(BIIB067)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>Tofersen (formerly IONIS-SOD1<sub>Rx</sub>) is an investigational antisense medicine we designed to inhibit the production of superoxide dismutase
      1, or SOD1, which is a well understood genetic cause of ALS. SOD1-<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ALS is a rare, fatal, neurodegenerative disorder caused by a mutation in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">SOD1</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> gene leading to a progressive loss of motor neurons. As a result,
        people with SOD1-ALS experience increasing muscle weakness, loss of movement, difficulty breathing and swallowing and eventually succumb to the disease. Current treatment options for people with SOD1-ALS are extremely limited, with no medicines
        that significantly slow disease progression. Tofersen is one of three medicines we have in development to treat ALS. </span>It is estimated that there are approximately 1,400 patients with SOD1-ALS in the G7 countries. Biogen is evaluating
      tofersen for treatment of patients with SOD1-ALS and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in presymptomatic individuals</span>.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen is currently under regulatory review in the U.S. and EU. In July 2022, Biogen announced that the FDA had accepted tofersen&#8217;s NDA
    and granted priority review of tofersen for SOD1-ALS. Tofersen has an FDA Advisory Committee meeting planned for March 22, 2023 and a PDUFA date of April 25, 2023. In December 2022, Biogen announced that the EMA accepted the MAA for tofersen for
    SOD1-ALS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The tofersen NDA and MAA included results from a Phase 1 study in healthy volunteers, a Phase 1/2 study evaluating ascending dose
    levels, the Phase 3 VALOR study, and the Phase 3 OLE study, as well as 12-month integrated results from VALOR and the Phase 3 OLE study. The 12-month integrated data show that earlier initiation of tofersen, compared to delayed initiation, slowed
    declines in clinical function, respiratory function, muscle strength and quality of life and build on the results previously observed in the initial readout. The 12-month data compare patients with early initiation of tofersen (at the start of VALOR)
    to those who had a delayed initiation of tofersen (six months later, in the OLE).</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the time of the 12-month analysis, because the majority of participants survived without permanent ventilation, or PV, the median time
    to death or PV and median time to death, could not be estimated. However, early survival data suggest a lower risk of death or PV and death with earlier initiation of tofersen. Additionally, the latest 12-month results showed that reductions in total
    SOD1 protein (a marker of target engagement) and neurofilament (a marker of axonal injury and neurodegeneration) were sustained over time. Tofersen reduced total cerebrospinal fluid, or CSF, SOD1 protein and plasma neurofilament levels in both early-
    and delayed-start groups as follows:</div>

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            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33% and 21% reduction in SOD1 protein, the intended target for tofersen, respectively</div>
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            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">51% and 41% reduction in plasma neurofilament, a marker of neuron injury, respectively</div>
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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tofersen had a favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, Biogen initiated a second Phase 3 study of tofersen, called ATLAS, in presymptomatic individuals with a SOD1
      genetic mutation. ATLAS is a multi-center, randomized, double-blind, placebo-controlled study enrolling approximately 150 subjects designed to assess the efficacy, safety and tolerability of tofersen. Patients are only given tofersen if they meet a
      defined biomarker threshold or progress to develop clinically manifest SOD1-ALS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2018, Biogen exercised its option to license tofersen. As a result, Biogen is responsible for global development, regulatory
    and commercialization activities, and costs for tofersen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Pelacarsen (Apo(a)) </span>(TQJ230)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Pelacarsen (formerly </span>IONIS-APO(a)-L<sub>Rx</sub>)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">is an investigational LICA antisense medicine we designed to inhibit the
      production of apolipoprotein(a), or Apo(a), in the liver to offer a direct approach for reducing Lp(a). Elevated Lp(a) is recognized as an independent, genetic cause of CVD. Lp(a) levels are determined at birth and lifestyle modification, including
      diet and exercise, do not impact Lp(a) levels. Inhibiting the production of Apo(a) in the liver reduces the level of Lp(a) in blood, potentially slowing down or reversing CVD in people with hyperlipoproteinemia(a), a condition in which individuals
      have levels of Lp(a) greater than 50 mg/dL, the recognized threshold for risk of CVD. We believe antisense technology is well suited to address hyperlipoproteinemia(a) because it specifically targets the RNA that codes for all forms of the Apo(a)
      molecule. It is estimated that there are more than eight million people living with CVD and elevated levels of Lp(a).</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019,<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>Novartis initiated the Phase 3 study
    of pelacarsen, Lp(a) HORIZON, in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">patients with </span>elevated Lp(a) levels and a prior cardiovascular event. Lp(a) HORIZON is <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">a global, multi-center, randomized, double-blind, placebo-controlled cardiovascular outcomes study in more than 8,000 patients designed to assess the efficacy, safety and tolerability of pelacarsen</span>. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Patients are treated with </span>80 mg of pelacarsen administered monthly by subcutaneous injection. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The
      primary endpoint in Lp(a) HORIZON is the time to occurrence of first major adverse cardiovascular event, or MACE. </span>In July 2022, we announced that the Lp(a) HORIZON study had completed enrollment.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2018, at the American Heart Association, or AHA, annual meeting, we reported results of the Phase 2 study of pelacarsen in
    patients with hyperlipoproteinemia(a). In the Phase 2 study, we observed statistically significant and dose dependent reductions from baseline in Lp(a) levels. Approximately 98 percent of patients who received the highest dose in the study demonstrated
    a reduction in Lp(a) levels to below the recommended threshold for CVD events (&lt;50 mg/dL). Pelacarsen had a favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In February 2019, Novartis exercised its option to license pelacarsen. As a result, Novartis is responsible for global development,
    regulatory and commercialization activities, and costs for pelacarsen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2020, the FDA granted pelacarsen fast track designation for the treatment of patients with elevated Lp(a) and CVD. In December
    2020, the Center for Drug Evaluation, or CDE, of China National Medical Products Administration granted breakthrough therapy designation to pelacarsen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Bepirovirsen (HBV) </span>(GSK3228836)<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> &#8211; </span>Bepirovirsen (formerly IONIS-HBV<sub>Rx</sub>) is an investigational antisense medicine we designed to inhibit the production of viral proteins
    associated with hepatitis B virus, or HBV. These include proteins associated with infection and replication, including the hepatitis B surface antigen, or HBsAg, which is present in both acute and chronic infections and is associated with a poor
    prognosis in people with chronic HBV infection.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">HBV infection is a serious health problem that can lead to significant and potentially fatal health conditions, including cirrhosis,
    liver failure and liver cancer. Chronic HBV infection is one of the most common persistent viral infections in the world, affecting nearly 300 million people and resulting in approximately 900,000 deaths annually. Currently available therapies,
    although effective in reducing circulating HBV in the blood, do not effectively inhibit HBV antigen production and secretion, which are associated with poor prognosis and increased risk of liver cancer.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, GSK initiated the Phase 3 program of bepirovirsen, B-Well, in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">patients with</span> chronic HBV. B-Well 1 and B-Well 2 are<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> global, multi-center, randomized, double-blind, placebo-controlled studies enrolling more
      than 500 patients each. GSK designed these studies to assess the efficacy, safety and tolerability of bepirovirsen</span>. The studies will have four stages: (1) a double-blind treatment period of 24 weeks with bepirovirsen or placebo, (2) Nucleoside
    Analogue, or NA, treatment for 24 weeks, (3) NA cessation with 24 week follow up or (4) continue on NA for 24 weeks, with follow up for a further 24 weeks for patients who stopped NA treatment at week 48. The arms will be stratified based on HBsAg
    levels with the first group including those with HBsAg levels &#8805; 100 IU/mL to &#8804; 1,000 IU/mL and the second group for those with HBsAg levels &gt;1,000 IU/mL to &#8804; 3,000 IU/mL at screening. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The primary endpoint is the number of patients achieving functional cure with baseline HBsAg </span>&#8804; 1,000 IU/mL. Functional cure is defined as a sustained suppression (24 weeks or longer) of HBV DNA (&lt; Lower Limit of
    Quantification, or LLOQ) while off all HBV treatments with HBsAg loss (&lt;0.05 IU/mL) with or without HBsAg after a finite duration of therapy<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, GSK presented end of treatment results from the Phase 2b B-CLEAR study of bepirovirsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>in patients with chronic HBV infection at the European Association for the Study of the Liver&#8217;s, or EASL, International Liver Congress. Additionally, in November 2022, GSK
    presented positive end of study data from the Phase 2b B-CLEAR study at the American Association for the Study of Liver Diseases, or AASLD. The end of study results showed that treatment with bepirovirsen resulted in sustained clearance of HBsAg and
    HBV DNA for 24 weeks after end of bepirovirsen treatment in people with chronic HBV infection. Treatment with bepirovirsen, with a loading dose at day four and 11, and at a dose of 300 mg per week for 24 weeks (treatment arm 1), resulted in 9% of
    patients on NA treatment and 10% of patients not on NA treatment achieving the primary outcome of HBsAg levels below the LLOQ and HBV DNA levels, both below the LLOQ, respectively. This is defined as a sustained response and was observed for 24 weeks
    post last dose. In the study, sustained response rates were higher in subjects with low baseline HBsAg (&lt; 1000 IU/mL) than in those with high baseline HBsAg (&gt;1000 IU/mL). Patients with low baseline HBsAg levels responded best to treatment with
    bepirovirsen with 16% and 25% of patients achieving the primary outcome in treatment arm one of the on NA and not on NA cohorts, respectively. Bepirovirsen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">had a favorable
      safety and tolerability profile supportive of continued development.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2019, GSK exercised its option to license our HBV program following the positive results of the Phase 2a study of bepirovirsen
    in patients with chronic HBV infection. As a result, GSK is responsible for global development, regulatory and commercialization activities, and costs for the HBV program.</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Neurological Medicines in Development</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">According to the National Institute of Neurological Disorders and Stroke, or NINDS, at the National Institutes of Health, or NIH, a
    third of the 7,000 known rare diseases are neurological disorders or thought to include a neurological component. We are currently investigating potential disease-modifying treatments for a broad range of neurological diseases affecting major regions
    of the brain and in the central nervous system cell types, including ATTRv-PN, ALS and Alzheimer&#8217;s disease.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Eplontersen </span>&#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION363</span> &#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Tofersen </span>&#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Zilganersen</span> &#8211; Zilganersen
    (formerly ION373) is an investigational antisense medicine targeting glial fibrillary acidic protein, or GFAP, mRNA we designed to inhibit the production of GFAP. We are developing zilganersen as a potential therapy for Alexander disease, or AxD. AxD
    is a rare, progressive and fatal neurological disease that affects the myelin sheath which protects nerve fibers. AxD is caused by a gain-of-function mutation in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">GFAP</span> gene and is characterized by progressive deterioration, including loss of skills and independence, generally leading to death in childhood or early adulthood.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Two major types of AxD have been defined. Type I onset typically occurs before four years of age and patients can experience head
    enlargement, seizures, limb stiffness, delayed or declining cognition, and lack of growth. Type II onset typically occurs after the age of four and symptoms can include difficulty speaking, swallowing, and making coordinated movements. AxD is most
    often fatal. There are treatments that can relieve symptoms, but there is no disease modifying therapy yet available to patients.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we initiated a pivotal study of zilganersen in patients with AxD. The Phase 2/3 study of zilganersen is a multi-center,
    double-blind, placebo-controlled, multiple-ascending dose study in approximately 55 patients with AxD designed to assess the efficacy, safety and tolerability of zilganersen. Patients will receive zilganersen or placebo for a 60-week period, after
    which all patients in the study will receive zilganersen for a 60-week open-label treatment period. The primary endpoint is the change from baseline in the 10-Meter Walk Test, or 10MWT.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-MAPT</span><sub style="font-weight: bold;">Rx</sub> (BIIB080) &#8211; IONIS-MAPT<sub>Rx</sub> is an investigational antisense medicine we designed to selectively inhibit production of the microtubule-associated protein tau, or tau protein in the brain. We are developing
    IONIS-MAPT<sub>Rx</sub> to treat people with Alzheimer&#8217;s disease, or AD, and potentially other neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain, such as certain forms of frontotemporal degeneration, or
    FTD, and progressive supranuclear palsy, or PSP.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AD and FTD are characterized predominantly by memory impairment and behavioral changes, resulting in a person&#8217;s inability to independently
    perform daily activities. PSP is characterized by problems with walking and control of movement, sleep disorder and loss of memory and ability to reason. AD generally occurs late in life and may progress to death in five to 20 years after the onset of
    the disease. FTD and PSP have a more rapid disease progression.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2022, Biogen initiated a Phase 2 clinical study of IONIS-MAPT<sub>Rx</sub> in patients with mild cognitive impairment or
    mild dementia due to AD. The study is a randomized, double-blinded, placebo-controlled, dose-escalation study in approximately 735 patients designed to assess the efficacy, safety and tolerability of IONIS-MAPT<sub>Rx </sub>administered<sub>&#160;</sub>intrathecally.
    The primary endpoint is the change from baseline to week 76 on the Clinical Dementia Rating scale Sum of Boxes, or CDR-SB.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2021, we and Biogen reported positive topline data from our Phase 1/2 study of IONIS-MAPT<sub>Rx</sub> in patients with mild
    Alzheimer&#8217;s disease at the Alzheimer&#8217;s Association International Conference, or AAIC. The Phase 1/2 study was a blinded, randomized, placebo-controlled, dose-escalation study of IONIS-MAPT<sub>Rx</sub> to evaluate the safety and activity of
    once-monthly intrathecal injections of IONIS-MAPT<sub>Rx</sub> in patients with mild AD. The study showed that IONIS-MAPT<sub>Rx</sub> met its primary objective of safety and tolerability in patients with mild Alzheimer&#8217;s disease. The study
    demonstrated robust time and dose dependent lowering of tau protein in cerebrospinal fluid over the three-month treatment period and sustained reductions during the six-month post-treatment period. IONIS-MAPT<sub>Rx</sub> had a favorable safety and
    tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub>. Biogen has responsibility for global development,
    regulatory and commercialization activities, and costs for IONIS-MAPT<sub>Rx</sub>.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION859 (LRRK2) </span>(BIIB094) &#8211;
    ION859 is an investigational antisense medicine we designed to inhibit the production of the Leucine Rich Repeat Kinase 2, or LRRK2, protein as a potential therapy for Parkinson&#8217;s disease, or PD. The most common genetic mutations in PD are found in the
    LRRK2 protein. It is believed that increased LRRK2 protein activity could be one of the key drivers for developing PD. PD is a progressive neurodegenerative disease characterized by loss of neurons in the motor system. Patients with PD can experience
    tremors, loss of balance and coordination, stiffness, slowing of movement, changes in speech and in some cases cognitive decline. PD is ultimately fatal. There are treatments that can relieve symptoms, but there are no approved disease modifying
    therapies.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2019, Biogen initiated a Phase 1/2 study evaluating ION859 in patients with PD. The Phase 1/2 study is a global, multi-center,
    randomized, double-blinded, placebo-controlled study in approximately 80 patients designed to assess the safety, tolerability and activity of multiple ascending doses of ION859 administered intrathecally.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION859 is being developed under our 2013 Strategic Neurology collaboration with Biogen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION464 (SNCA)</span> (BIIB101) &#8211; ION464
    is an investigational antisense medicine we designed to inhibit the production of the alpha-synuclein protein as a potential therapy for PD, Multiple System Atrophy, or MSA, and related synucleinopathies. Alpha-synuclein protein abnormally accumulates
    in the brains of PD and MSA patients and is thought to be one of the key drivers of these diseases. It is believed that decreasing the production of the alpha-synuclein protein will reduce the toxic effects of gain-of-function mutations.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2020, we initiated a Phase 1/2 study evaluating ION464 in patients with MSA. The current study is a multi-center, randomized,
    double-blinded, placebo-controlled study in approximately 40 patients designed to assess the safety and tolerability of multiple ascending doses of ION464 administered intrathecally.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION464 is being developed under our 2013 Strategic Neurology collaboration with Biogen.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION541 (ATXN2) </span>(BIIB105) &#8211; ION541
    is an investigational antisense medicine we designed to reduce the production of the ataxin-2, or ATXN2, protein for the potential treatment of ALS. The reduction of ATXN2 has been shown to decrease aggregation of TDP-43, a toxic RNA binding protein
    found in most patients with ALS, including the approximately 90 percent of the ALS population with no known family history of ALS.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, Biogen initiated a Phase 1/2 clinical study evaluating ION541 in patients with ALS. The current study is a randomized,
    blinded, placebo-controlled study in approximately 110 patients designed to assess the safety, tolerability, and pharmacokinetics of multiple ascending doses of ION541 administered intrathecally.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION541 is being developed under our 2013 Strategic Neurology collaboration with Biogen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION582 (UBE3A)</span> (BIIB121) &#8211; ION582
    is an investigational antisense medicine we designed to inhibit the expression of the UBE3A transcript, or UBE3A-ATS for the potential treatment of Angelman Syndrome, or AS. AS is a rare, genetic neurological disease caused by the loss of function of
    the maternally inherited <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">UBE3A</span> gene. AS typically presents in infancy and is characterized by intellectual disability, balance issues, motor
    impairment, and debilitating seizures. Some patients are unable to walk or speak. Some symptoms can be managed with existing drugs; however, there are no approved disease modifying therapies.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we initiated the Phase 1/2 study, HALOS, of ION582 in patients with AS. The study is an open label dose-escalation
    study enrolling approximately 40 patients designed to assess the safety, tolerability and activity of multiple ascending doses of ION582.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION582 is being developed under our 2012 Neurology collaboration with Biogen.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Tominersen (HTT)</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (</span>RG6042<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">) &#8211; </span>Tominersen (formerly IONIS-HTT<sub>Rx</sub>) is an
    investigational antisense medicine we designed to target the underlying cause of Huntington&#8217;s disease, or HD, by reducing the production of all forms of the huntingtin protein, or HTT, including its mutated variant, or mHTT. HD is an inherited genetic
    brain disorder that results in the progressive loss of both mental faculties and physical control. It is caused by the expansion of the cytosine-adenine-guanine, or CAG, trinucleotide sequence in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">HTT</span> gene. The resulting mutant HTT protein is toxic and gradually destroys neurons. Symptoms usually appear between the ages of 30 and 50 and worsen over a 10 to 25-year period. Ultimately, the
    weakened individual succumbs to pneumonia, heart failure or other complications. Presently, there is no effective treatment or cure for the disease, and currently available medicines only mask the patient&#8217;s symptoms but do not slow down the underlying
    loss of neurons.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients aged 25 to 50 years old with prodromal and
    early manifest HD. The Phase 2 study of tominersen is a multi-center, double-blind, placebo-controlled study in approximately 360 patients designed to assess the efficacy, safety and tolerability of tominersen. Patients will receive tominersen or
    placebo every 16 weeks for 16 months, after which patients may receive tominersen in an open-label study. The primary endpoint is the change from baseline in the composite Unified Huntington&#8217;s Disease Ratings Scale, or cUHDRS, (non-U.S.) and overall
    functional capacity, or TFC, (U.S.) at 16 months.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche conducted the Phase 3 study, GENERATION HD1, of tominersen in patients with HD. The Phase 3 study was a randomized, multicenter,
    double-blind, placebo-controlled study that recruited 791 participants. In March 2021, Roche announced that dosing would be stopped in the study following a recommendation from the independent data monitoring committee, or iDMC, based on an overall
    benefit/risk assessment. In January 2022, Roche announced findings from a post-hoc analysis of the GENERATION HD1 study that suggested tominersen may benefit younger adult patients with lower disease burden.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2017, Roche exercised its option to license tominersen. As a result, Roche is responsible for global development, regulatory
    and commercialization activities, and costs for tominersen.</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Our Cardiovascular Medicines in Development</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">According to the World Health Organization, or WHO, CVD remains the number one cause of death globally. An estimated 17.9 million people
    died from CVD in 2019, representing approximately 30 percent of all deaths globally. Our cardiovascular medicines target the major risk factors of cardiovascular disease, including cholesterol, triglycerides, and hypertension.</div>

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  <div style="text-align: center;"><img width="717" height="198" src="image4.jpg" alt="graphic" /></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Eplontersen </span>&#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Olezarsen </span>&#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Pelacarsen </span>&#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Fesomersen (FXI)</span> &#8211; Fesomersen
    (formerly IONIS-FXI-L<sub>Rx</sub>) is an investigational LICA medicine we designed to inhibit the production of Factor XI. Factor XI is a clotting factor produced in the liver that is important in the growth of blood clots. Thrombosis, characterized
    by the formation of a blood clot inside blood vessels, can cause heart attacks and strokes. People who are deficient in Factor XI have a lower incidence of thromboembolic events with minimal increase in bleeding risk. Although currently available
    anticoagulants reduce the risk of thrombosis, physicians associate these anticoagulants with increased bleeding, which can be fatal. By inhibiting Factor XI production, we believe that fesomersen can be used for the treatment of a number of non-acute
    forms of thrombosis where additional safe and well tolerated anti-thrombotic medicines are needed.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, Bayer presented positive results from the RE-THINc Phase 2b study of fesomersen in patients with end-stage renal
    disease, or ESRD, on hemodialysis at the American Society of Nephrology&#8217;s, or ASN, Kidney Week. In the study, fesomersen achieved its primary endpoint, demonstrating no increase in the incidence of the composite of major bleeding and clinically
    relevant non-major bleeding with 24 weeks of treatment. Fesomersen also achieved dose-dependent and sustained median reductions in steady-state FXI levels of 53.1%, 72.2% and 86.6% in the 40 mg, 80 mg, and 120 mg doses of fesomersen, respectively,
    administered once every four weeks. Incidences of dialysis circuit clotting and arteriovenous access, or AV-access, thrombosis diminished significantly with decreasing FXI levels, both of which were exploratory efficacy endpoints. Fesomersen had a
    favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we regained all rights to fesomersen, which we had previously licensed to Bayer in February 2017.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-AGT-L</span><sub style="font-weight: bold;">Rx</sub>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211;</span> IONIS-AGT-L<sub>Rx</sub> is an investigational LICA medicine we designed to inhibit the production of
    angiotensinogen to decrease blood pressure in people with uncontrolled hypertension. Treatment resistant hypertension, or TRH, is defined as failure to achieve a blood pressure goal of 140/90 (systolic/diastolic) despite the use of three or more
    antihypertensive medications. People with TRH have been found to have a three-fold higher chance of having fatal and non-fatal cardiovascular events relative to those with controlled hypertension.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also studying IONIS-AGT-L<sub>Rx</sub> in patients with chronic heart failure with reduced ejection fraction. Heart failure, or
    HF, is a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body&#8217;s needs for blood and oxygen. HF with reduced ejection fraction is a clinical syndrome of shortness of breath, exercise intolerance and/or
    fluid retention resulting from an impairment of ejection of blood, usually documented by a left ventricular ejection fraction of 40 percent or less on echocardiography.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021, we initiated a Phase 2b clinical study of IONIS-AGT-L<sub>Rx</sub> in patients with TRH. The study is a randomized,
    double-blinded, placebo-controlled study in approximately 150 patients designed to assess the efficacy, safety and tolerability of IONIS-AGT-L<sub>Rx</sub>. The primary endpoint is the change in systolic blood pressure, or SBP, from baseline.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2021, we initiated a Phase 2 clinical study of IONIS-AGT-L<sub>Rx</sub> in patients with chronic HF with reduced ejection
    fraction. The study is a randomized, double-blind, placebo-controlled study in approximately 75 patients designed to assess the safety, tolerability, and efficacy of IONIS-AGT-L<sub>Rx</sub>. The primary endpoint is the percent change in plasma AGT
    concentration from baseline.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated IONIS-AGT-L<sub>Rx</sub> in two randomized, double-blinded, placebo-controlled Phase 2 studies. The first study was in
    people with mild hypertension and the second was in people with uncontrolled hypertension who were on two or three antihypertensive medications, including ACE inhibitors or ARBs.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> IONIS-AGT-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> significantly reduced AGT levels compared to placebo in both studies. IONIS-AGT-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> had a favorable safety and tolerability profile supportive of continued development.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION904</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#8211;</span> ION904 is an investigational next-generation LICA medicine designed to inhibit the production of angiotensinogen to decrease blood pressure in people with uncontrolled
    hypertension. ION904 is a follow-on medicine targeting AGT, designed to enable less frequent dosing compared to IONIS-AGT-L<sub>Rx</sub>.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2022, we initiated a Phase 2 clinical study of ION904 in patients with mild to moderate uncontrolled hypertension on one or
    more anti-hypertensive medications for at least one month. The study is a randomized, double-blind, placebo-controlled study in approximately 45 patients designed to assess the safety, tolerability, and efficacy of ION904. The primary endpoint is the
    percent change in plasma AGT concentration from baseline.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted a Phase 1, blinded, randomized, placebo-controlled, dose-escalation study of ION904 in healthy volunteers that was
    supportive of continued development.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Specialty Rare Medicines in Development</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our emerging specialty rare disease pipeline is comprised of medicines that are outside of our cardiovascular and neurological
    franchises, but we believe could represent a compelling opportunity for us.</div>

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  <div style="text-align: center;"><img width="712" height="78" src="image5.jpg" alt="graphic" /></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Donidalorsen</span> &#8211; See the medicine
    description under &#8220;Our Late-Stage Pipeline&#8221; section above.</div>

  <div style="text-align: justify; text-indent: 35.3pt; margin-top: 12pt; margin-bottom: 12pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Sapablursen
      (TMPRSS6)</span> &#8211; Sapablursen (formerly IONIS-TMPRSS6-L<sub>Rx</sub>) is an investigational LICA medicine we designed to target the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">TMPRSS6</span> gene
    to modulate the production of hepcidin, which is the key regulator of iron homeostasis. By modulating hepcidin expression, sapablursen has the potential to positively impact diseases characterized by iron deficiency, such as polycythemia vera, or PV.</div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PV is a rare, non-genetic and potentially fatal disease caused by overproduction of red blood cells. This overproduction leads to a
    thickening of the blood, which increases patients&#8217; risk of life-threatening blood clots, including in the lungs, heart and brain. Patients with PV also experience severe iron deficiency due to hepcidin overexpression. There are no approved
    disease-modifying treatments for PV.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we initiated a Phase 2 study evaluating sapablursen in patients with phlebotomy dependent PV, or PD-PV. The Phase 2
    study is a multi-center, randomized, open-label study in approximately 40 patients designed to assess the efficacy, safety and tolerability of sapablursen. The primary endpoint is the change in the frequency of phlebotomy comparing baseline with the
    last 20 weeks of the 37-week treatment period.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2018, we presented positive data from our Phase 1 study of sapablursen in healthy volunteers at the American Society of
    Hematology Annual Meeting. The Phase 1 study demonstrated dose-dependent reductions of serum iron and serum transferrin saturation with sapablursen. Additionally, we observed an increase in serum hepcidin and predicted changes in hemoglobin.
    Sapablursen had a favorable safety and tolerability profile supportive of continued development.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Medicines in Development</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have four medicines in development, outside of our core franchises, of which half are partnered.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Bepirovirsen</span> &#8211; <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">See the medicine description under &#8220;Our </span>Late-Stage Pipeline<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#8221; section above.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">IONIS-FB-L</span><sub style="font-weight: bold;">Rx</sub> &#8211; <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (RG6299) is an
      investigational LICA medicine we designed to inhibit the production of complement factor B, or FB, and the alternative complement pathway. Genetic association studies have shown that overaction of the alternative complement pathway has been
      associated with the development of several complement-mediated diseases, including immunoglobulin A, or IgA, nephropathy, or IgAN, and geographic atrophy, or GA, secondary to age-related macular degeneration, or AMD.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IgAN is one of the most common causes of inflammation that impairs the filtering ability of kidneys and is an important cause of chronic
    kidney disease and kidney failure. Also known as Berger&#8217;s disease, IgAN is characterized by deposits of IgA in the kidneys, resulting in inflammation and tissue damage. AMD is the leading cause of central vision loss in developed countries. GA is an
    advanced form of AMD.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we presented positive results from the Phase 2 study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN at the American
    Society of Nephrology&#8217;s, or ASN, Kidney Week. In the Phase 2 study, which included results from the first 10 patients treated with IONIS-FB-L<sub>Rx</sub>, IONIS-FB-L<sub>Rx</sub> met its primary endpoint of change in 24-hour urinary protein,
    demonstrating a 44% mean reduction in proteinuria from baseline to week 29. Kidney function, as measured by estimated glomerular filtration rate, or eGFR, was maintained in all patients in the study. The results from the Phase 2 study provided
    proof-of-concept for the potential of IONIS-FB-L<sub>Rx</sub> to treat patients with IgAN by inhibiting complement FB and the alternative complement pathway. IONIS-FB-L<sub>Rx</sub> had a favorable safety and tolerability profile supportive of
    continued development. The Phase 2 open-label study remains ongoing and will evaluate IONIS-FB-L<sub>Rx</sub> in approximately 25 patients with IgAN.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In June 2019, we initiated a Phase 2 study evaluating
      IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in patients with GA secondary to age-related macular degeneration. The study is a randomized, masked, placebo-controlled study in
      approximately 330 patients designed to assess the efficacy, safety and tolerability of multiple ascending doses of IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> administered subcutaneously
      in adults with GA.</span> The primary endpoint is the absolute change from baseline in GA area at week 49.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2022, Roche exercised its option to license IONIS-FB-L<sub>Rx</sub> following the positive Phase 2 results described above.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Cimdelirsen (GHR) </span>&#8211; Cimdelirsen
    (formerly IONIS-GHR-L<sub>Rx</sub>) is an investigational LICA medicine we designed to inhibit the production of growth hormone receptor, or GHr, to decrease the circulating level of insulin-like growth factor-1, or IGF-1. Elevated levels of IGF-1
    results in acromegaly, a chronic, slowly progressing and potentially fatal disease. Patients with acromegaly experience multiple chronic conditions, such as type 2 diabetes, hypertension, respiratory complications and premature death. Current
    treatments to block IGF-1 are often unsuccessful. Drug treatments to normalize IGF-1 levels are also available but are associated with potentially serious side effects.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2021, we initiated a Phase 2 study </span>evaluating
    cimdelirsen as a monotherapy <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in patients with acromegaly. The Phase 2 study is a multi-center, randomized, open label study in approximately 40 patients designed to assess
      the efficacy, safety and tolerability of </span>cimdelirsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span> The primary endpoint is the percent change from baseline in IGF-1 to week 27.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We completed a Phase 2 study evaluating cimdelirsen as an
      add-on therapy in patients with uncontrolled acromegaly despite stable therapy with long-acting somatostatin receptor ligands, or SRL. Due to enrollment difficulties associated with the COVID-19 pandemic, the study closed early, resulting in smaller
      cohort sizes than planned. While no longer powered to assess the primary endpoint (percentage of IGF- lowering at Day 141) in accordance with the protocol, the study did permit placebo-controlled evaluation of safety and efficacy. </span>Cimdelirsen
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">had a favorable safety and tolerability profile supportive of continued development.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">ION224</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">(DGAT)</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> &#8211;
    </span>ION224 is an investigational LICA medicine we designed to reduce the production of diacylglycerol acyltransferase 2, or DGAT2, to treat patients with nonalcoholic steatohepatitis, or NASH. NASH is a common liver disease characterized by liver
    steatosis, inflammation and scarring and can lead to increased risk of cardiovascular disease, liver cancer, need for liver transplantation and early death. DGAT2 is an enzyme that catalyzes the final step in triglyceride synthesis in the liver.
    Reducing the production of DGAT2 should therefore decrease triglyceride synthesis in the liver. In animal studies, antisense inhibition of DGAT2 significantly improved liver steatosis, lowered blood lipid levels and reversed diet-induced insulin
    resistance.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nonalcoholic fatty liver disease, or NAFLD, describes the full spectrum of liver disease progression from fatty liver to NASH to
    cirrhosis to hepatocellular carcinoma. NASH epidemiology studies have estimated 13 to 32 percent of the global population has NAFLD, 1.5 to 6.5 percent have NASH, and approximately nine percent of NASH patients progress to advanced liver disease. There
    are currently no commercially available medications to treat NASH.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NASH is sometimes considered a &#8220;silent&#8221; liver disease because people with early-stage NASH feel well, even though they are starting to
    accumulate fat in their livers and may not be aware that they have the disease. However, NASH can develop into more severe diseases such as liver cirrhosis and liver failure. Currently, liver transplant is the only therapeutic option for patients with
    liver cirrhosis. In addition, NASH has been shown to be a major risk factor for the development of liver cancer.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2021, we initiated a Phase 2 study of ION224 in patients with <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">confirmed non-alcoholic steatohepatitis. The Phase 2 study is </span>a multi-center, randomized, double-blind, placebo-controlled clinical study in approximately 160 patients <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">designed to assess the efficacy, safety and tolerability of multiple </span>subcutaneous<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> doses of ION224 on NASH histologic improvement.</span></div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our Technology</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For more than 30 years, we have advanced genetic medicines with the goal to change standards of care and transform the lives of people
    with devastating diseases. Our recent technology advancements have enabled us to advance programs with the potential for extended dosing and delivery to new tissues, such as muscle. We also recently added capabilities to potentially utilize RNA
    interference, or RNAi, or gene editing in addition to our novel antisense technology,&#160; which we believe, gives us the potential to deliver genetic medicines for a greater number of patients in need.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Overview of Antisense Technology</div>

  <div style="text-align: justify; text-indent: 35.3pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of the medicines currently in our clinical pipeline use our antisense technology &#8212; an innovative platform for discovering
    first-in-class and/or best-in-class medicines. Antisense medicines target RNA, the intermediary that conveys genetic information from a gene to the protein synthesis machinery in the cell. By targeting RNA instead of proteins, we can use antisense
    technology to increase, decrease or alter the production of specific proteins. Most of our antisense medicines are designed to bind to mRNAs and inhibit the production of disease-causing proteins. Examples of these include eplontersen, olezarsen and
    donidalorsen. SPINRAZA is an example of an antisense medicine that modulates RNA splicing to increase protein production of the SMN protein, which is critical to the health and survival of nerve cells in the spinal cord that are responsible for
    neuro-muscular function. The SMN protein is deficient in people with SMA. Our antisense technology is also broadly applicable to many additional antisense mechanisms including decreasing toxic RNAs.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our advanced LICA technology is a chemical technology we developed that involves attaching a molecule called a ligand that binds with
    receptors on the surfaces of cells in a highly specific manner. Because these receptors are often found only on certain cell types, LICA allows us to increase effective delivery of our antisense medicines with higher specificity to certain cell types
    that express these receptors relative to non-conjugated antisense medicines. We currently have an integrated assessment of data from multiple LICA medicines and clinical programs which demonstrates that our LICA technology for liver targets can
    increase potency by 20-30-fold over our non-LICA antisense medicines. Our LICA medicines have also demonstrated consistently favorable safety and tolerability in clinical trials. In 2022, we reported positive interim analysis data from the
    NEURO-TTRansform study of eplontersen in patients with ATTRv-PN. Eplontersen demonstrated a favorable safety and tolerability profile with no specific concerns.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our generation 2.5 chemistry can enable up to 10-fold greater potency compared to our medicines using our Generation 2 chemistries. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We can combine our Generation 2.5 chemistry with our LICA technology to further increase potency.</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, we are developing LICA conjugation technology that we can use to target tissues other than the liver, such as muscle, and
    initial results in animals are promising. In the fourth quarter of 2022, we advanced our first program incorporating LICA technology for enhanced delivery to muscle into preclinical development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Emerging Technology Advancements</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our recent technology advancements have enabled us </span>to
    create even more potent medicines amenable to more potential targets and tissue types. We have also diversified the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">approaches we can use in designing our medicines in order
      to reach more patients with severe diseases.</span> Today our medicines and those entering our pipeline utilize our key technology advances, including our LICA technology and mesyl phosphoramidate, or MsPA, backbone chemistry. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> may also now be able to use RNAi in addition to antisense, in the development of new medicines, depending on which approach demonstrates the best potential product profile for
      the indication we are pursuing. And through our Metagenomi collaboration, we added the potential to use gene editing, which modifies DNA.</span></div>

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  <div style="text-align: justify; margin-left: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Mesyl phosphoramidate Backbone Chemistry</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We designed our MsPA backbone chemistry to improve both therapeutic index and durability. It does this by increasing metabolic stability
    relative to the other backbone chemistries we utilize. We have also shown it can improve potency in certain circumstances and reduce non-specific interactions with proteins that can cause undesirable effects, such as proinflammatory effects. In the
    fourth quarter of 2022, we advanced new programs using our MsPA backbone, designed to improve both efficacy and durability, into preclinical development.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Gene Editing and Metagenomi Collaboration</span></div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we entered into a collaboration with Metagenomi that leverages our extensive expertise in RNA-targeted therapeutics
    and Metagenomi&#8217;s versatile next-generation gene editing systems to pursue a mix of validated and novel genetic targets with the goal of discovering and developing new drugs. These targets have the potential to expand therapeutic options for patients.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene editing utilizes specific RNA-guided nucleases known as Cas enzymes to precisely and permanently modify a DNA sequence. Because of
    this, gene editing holds the promise of treatments that could provide long-term, potentially permanent, therapeutic benefits.</div>

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  <div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene editing is highly complementary and synergistic with RNA-targeted therapeutics. Both platforms rely on the same nucleic acid
    hybridization principals to precisely target nucleases to either RNA, in the case of RNase H and siRNA drugs, or to DNA in the case of Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR-Cas systems. This enables us to leverage our
    expertise in nucleic acids and modified nucleic acid chemistry with the goal to enhance gene editing&#8217;s ability to treat diseases for which there are limited treatment options.</div>

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  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Collaborative Arrangements</div>

  <div><br />
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have established alliances with a cadre of leading global pharmaceutical companies. Our partners include the following companies,
      among others: AstraZeneca, Biogen, GSK, Novartis and Roche. Through our partnerships, we have earned both commercial revenue and a broad and sustaining base of R&amp;D revenue in the form of license fees, upfront payments and milestone payments. In
      2022, we recognized $587 million in revenue, the majority of which was from our partnered medicines and programs. We have the potential to earn more than $23 billion in future milestone payments, licensing fees and other payments from our current
      partnerships. In addition, we are eligible to receive up to mid-20 percent royalties under our partnerships. Below, we include the significant terms of our collaboration agreements. For additional details, including other financial information, refer
      to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements,</span> in the Notes to the Consolidated Financial Statements.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>

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  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>

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    <div><br />
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using our technology to advance the treatment of neurological disorders.
    These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with SMA. We and
    Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under our collaborations, including medicines in development to treat people with ALS, SMA, AS, Alzheimer&#8217;s disease<sub>&#160;</sub>and Parkinson&#8217;s
    disease. In addition to these medicines, our collaborations with Biogen include a substantial pipeline that addresses a broad range of neurological diseases. From inception through December 31, 2022, we have generated more than $3.5 billion in payments
    from our Biogen collaborations.</div>

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    <div><br />
    </div>

  </div>

  <div>
    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Spinal Muscular Atrophy Collaborations</div>

    <div><br />
    </div>

    <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

    <div><br />
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement
      with Biogen to develop and commercialize SPINRAZA, an RNA-targeted therapy for the treatment of SMA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are receiving tiered royalties ranging from 11 percent to 15
      percent on sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single
      digit royalty on net sales of SPINRAZA. Under our agreement, Biogen is responsible for global development, regulatory and commercialization activities and costs for SPINRAZA. From inception through December 31, 2022, we recognized more than $</span>1.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including
      nearly $1.4 billion in revenue from SPINRAZA royalties and more than $425 million in R&amp;D revenue.</span></div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New antisense medicines for the treatment of SMA</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2017, we entered into a collaboration agreement with Biogen to identify new antisense medicines for the treatment of SMA.
    Biogen has the option to license therapies arising out of this collaboration following the completion of preclinical studies. Upon licensing, Biogen will be responsible for global development, regulatory and commercialization activities and costs for
    such therapies. Under the collaboration agreement, we received a $25 million upfront payment in December 2017. In December 2021, Biogen exercised its option to license ION306, for which we earned a $60 million license fee payment. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen is solely responsible for the costs and expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will receive development and regulatory milestone payments from Biogen if new medicines, including ION306, advance towards marketing
    approval.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $1.2 billion, which is comprised of a $25 million upfront payment, up
    to $110 million in license fees, up to $80 million in development milestone payments, up to $180 million in regulatory milestone payments and up to $800 million in sales milestone payments and other payments, including up to $555 million if Biogen
    advances ION306. In addition, we are eligible to receive tiered royalties from the mid-teens to mid-20 percent range on net sales from any product that Biogen successfully commercializes under this collaboration. From inception through December 31,
    2022, we have generated $85 million in payments under this collaboration.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2018 Strategic Neurology</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2018, we and Biogen entered into a strategic collaboration agreement to develop novel antisense medicines for a broad range of
    neurological diseases. We also entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for these diseases for 10 years. We are responsible
    for the identification of antisense drug candidates based on selected targets. Biogen will usually be responsible for conducting IND-enabling toxicology studies for the selected medicine. Biogen has the option to license the selected medicine after it
    completes the IND-enabling toxicology study. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2018, we received $1 billion from Biogen, comprised of $625 million to purchase our stock at an approximately 25 percent cash
    premium and $375 million in an upfront payment.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $270 million, which is comprised of a $15 million license fee, up to
    $105 million in development milestone payments and up to $150 million in regulatory milestone payments for each medicine that achieves marketing approval. In addition, we are eligible to receive tiered royalties up to the 20 percent range on net sales
    from any product that Biogen successfully commercializes under this collaboration. We are currently advancing multiple programs under this collaboration. From inception through December 31, 2022, we have generated nearly $1.1 billion in payments under
    this collaboration.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2013 Strategic Neurology</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the
    treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this
    collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen will have the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration
    to include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently
    advancing five investigational medicines in development under this collaboration, including a medicine for Parkinson&#8217;s disease, two medicines for ALS, a medicine for multiple system atrophy and a medicine for an undisclosed target. In December 2018,
    Biogen exercised its option to license our most advanced ALS medicine, tofersen, and as a result Biogen is responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license
    fees and royalty payments for all medicines developed under this collaboration, with the specific amounts dependent upon the modality of the molecule advanced by Biogen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration for tofersen, we are eligible to receive nearly $110 million, which is comprised of a $35 million
    license fee, up to $18 million in development milestone payments and $55 million in regulatory milestone payments. For each of the other antisense medicines that are chosen for drug discovery and development under this collaboration, we are eligible to
    receive up to approximately $260 million, which is comprised of a $70 million license fee, up to $60 million in development milestone payments and up to $130 million in regulatory milestone payments. In addition, we are eligible to receive tiered
    royalties up to the mid-teens on net sales from any product that Biogen successfully commercializes under this collaboration. From inception through December 31, 2022, we have generated more than $300 million under this collaboration, including more
    than $25 million in milestone payments we received from Biogen in 2022 when Biogen advanced three programs under this collaboration.</div>

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    <div><br />
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat
    neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through
    the completion of the first Phase 2 study for each program. Under this collaboration, Biogen is conducting the IONIS-MAPT<sub>Rx</sub> study for AD and we are currently advancing ION582 for AS. If Biogen exercises its option to license a medicine, it
    will assume global development, regulatory and commercialization responsibilities and costs for that medicine. In December 2019, Biogen exercised its option to license IONIS-MAPT<sub>Rx</sub> and as a result Biogen is responsible for global
    development, regulatory and commercialization activities and costs for IONIS-MAPT<sub>Rx</sub>.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $30 million. Over the term of the collaboration, we are eligible to
    receive up to $210 million, which is comprised of a $70 million license fee, up to $10 million in development milestone payments per program and up to $130 million in regulatory milestone payments per program, plus a mark-up on the cost estimate of the
    Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales from any product that Biogen successfully commercializes under this collaboration. From inception through December 31, 2022, we have
    generated more than $190 million under this collaboration, including nearly $20 million in milestone payments we received from Biogen for advancing ION582 and a $10 million milestone payment we received from Biogen when Biogen advanced IONIS-MAPT<sub>Rx</sub>
    during 2022.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Joint Development and Commercialization Arrangement</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in
    Latin America.</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The collaboration also includes territory-specific development, commercial and medical affairs cost-sharing provisions. AstraZeneca is
    currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. AstraZeneca is responsible for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing
    eplontersen to market outside the U.S.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. In addition, we are eligible to receive up to
      mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S. From inception through December 31, 2022, we have generated more than $275 million in payments under this collaboration, including
      more than $75 million we earned from cost sharing provisions in 2022.</span></div>

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  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research and Development Partners</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our collaboration for eplontersen, we have a collaboration with AstraZeneca focused on discovering and developing
    treatments for cardiovascular, renal and metabolic diseases. In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration,
    AstraZeneca has licensed multiple medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $5.8 billion, which is comprised of a $65 million upfront payment, up
    to $290 million in license fees, up to $1.1 billion in development milestone payments, up to $2.9 billion in regulatory milestone payments and up to $1.5 billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up
    to the low teens on net sales from any product that AstraZeneca successfully commercializes under this collaboration agreement. From inception through December 31, 2022, we have generated $285 million in payments under this collaboration.</div>

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  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">GSK</div>

  </div>

  <div>
    <div><br />
    </div>

  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases. Our collaboration with GSK covers bepirovirsen<sub>,</sub> an investigational antisense medicine we designed to reduce the production of viral proteins associated with HBV
    infection. In 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to
    $42.5 million in development milestone payments, up to $120 million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops bepirovirsen. In addition, we are eligible to receive tiered royalties
    up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2022, we have generated more than $50 million in payments under the HBV program collaboration. Subsequent to December 31, 2022, we earned a $15 million milestone
    payment when GSK initiated a Phase 3 study of bepirovirsen in patients with chronic HBV in January 2023.</div>

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  <div>
    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Novartis</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis
      to develop and commercialize pelacarsen.</span> Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study, which Novartis initiated in December
    2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would negotiate the
    co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales of pelacarsen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a
    $150 million license fee, a $25 million development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. We are also eligible to receive tiered royalties in the mid-teens to low 20
    percent range on net sales of pelacarsen. From inception through December 31, 2022, w<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e have generated nearly $275 million in payments under this collaboration.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of
    our common stock for $100 million in the first quarter of 2017.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Roche</div>

  <div>
    <div><br />
    </div>

  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>

  <div>
    <div><br />
    </div>

  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2013, we entered into an agreement with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop
      treatments for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people
      with early-stage HD. In December 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen<sub>&#160;</sub>and is now responsible for the global development, regulatory and commercialization activities and costs for
      tominersen.</div>

    <div><br />
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment,
      a $45 million license fee, up to $70 million in development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up
      to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales from any product resulting from this collaboration. From inception through
      December 31, 2022, we have generated more than $150 million in payments under this collaboration.</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">IONIS-FB-L<sub>Rx</sub> for Complement-Mediated Diseases</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L<sub>Rx</sub> for the treatment of
    complement-mediated diseases. We are currently conducting Phase 2 studies in two disease indications for IONIS-FB-L<sub>Rx</sub>, one for the treatment of patients with GA, the advanced stage of dry AMD, and a second for the treatment of patients with
    IgA nephropathy. After receiving positive data from the Phase 2 clinical study of IONIS-FB-L<sub>Rx</sub> in patients with IgAN, Roche licensed IONIS-FB-L<sub>Rx</sub> in July 2022. As a result, Roche is responsible for global development, regulatory
    and commercialization activities, and costs for IONIS-FB-L<sub>Rx</sub>, except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive more than $810 million, which is comprised of a $75 million upfront
    payment, a $35 million license fee, up to $145 million in development milestone payments, up to $279 million in regulatory milestone payments and up to $280 million in sales milestone payments. In addition, we are also eligible to receive tiered
    royalties from the high teens to 20 percent on net sales. From inception through December 31, 2022, we have generated more than $130 million under this collaboration, including $55 million in payments we earned in 2022 for advancing IONIS-FB-L<sub>Rx</sub>.</div>

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  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercialization Partnerships</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution
    agreements with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each
    medicine.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, we entered into an exclusive license
      agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on net sales for each medicine. </span>In December 2021, we started receiving
    royalties from PTC for TEGSEDI sales<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We expect to receive royalties from PTC for WAYLIVRA sales starting in 2023.</span></div>

  <div>
    <div><br />
    </div>

  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Technology Enhancement Collaborations</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle Therapeutics License Agreement</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a collaboration agreement with Bicycle Therapeutics, or Bicycle, and obtained an option to license its
    peptide technology to potentially increase the delivery capabilities of our LICA medicines. In July 2021, we paid $42 million when we exercised our option to license Bicycle&#8217;s technology, which included an equity investment in Bicycle. As part of our
    stock purchase, we entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for one year. As a result, we recorded a $7 million equity investment for the shares we received in Bicycle in 2021. We recognized
    the remaining $35 million as R&amp;D expense in 2021. From inception through December 31, 2022, we have paid Bicycle $47 million under this collaboration agreement.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize
    investigational medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid $80 million to license Metagenomi&#8217;s
    technologies. We will also pay Metagenomi certain fees for the selection of genetic targets, and contingent on the achievement of certain development, regulatory and sales events, milestone payments and royalties. In addition, we will reimburse
    Metagenomi for certain of its costs in conducting its research and drug discovery activities under the collaboration.</div>

  <div>
    <div><br />
    </div>

    <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Other Agreements</div>

  </div>

  <div>
    <div><br />
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>

    <div><br />
    </div>

    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, Alnylam gave us a
      technology access fee, participation in fees from Alnylam&#8217;s partnering programs, as well as future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to four therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four targets, including FXI and
      Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific intellectual property for oligonucleotides against four other targets. Alnylam also
      granted us a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform
      technology arising from May 2014 through April 2019 for double-stranded RNAi therapeutics.</div>

  </div>

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  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41 million for
      payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41 million payment from Alnylam as R&amp;D revenue in the fourth quarter of 2020.</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Manufacturing</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We manufacture most of the active pharmaceutical ingredient, or API, we use for our research and development activities ourselves. We have
    also manufactured API and commercial supply for our approved medicines. We have dedicated significant resources to develop ways to improve manufacturing efficiency and capacity. Since we can use variants of the same nucleotide building blocks and the
    same type of equipment to produce our oligonucleotide medicines, we found that the same techniques we used to efficiently manufacture one oligonucleotide medicine could help improve the manufacturing processes for our other medicines. By developing
    several proprietary chemical processes to scale up our manufacturing capabilities, we have greatly reduced the cost of producing oligonucleotide medicines. For example, we have significantly reduced the cost of raw materials through improved yield
    efficiency, while at the same time increasing our capacity to make our medicines. Through both our internal research and development programs and collaborations with outside vendors, we may achieve even greater efficiency and further cost reductions.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing facility is located in a 26,800 square foot building in Carlsbad, California. We purchased this building in 2017. In
    addition, we have a 25,800 square foot building that houses support functions for our manufacturing activities. We lease this facility under a lease that has a term ending in August 2026 with an option to extend the lease for an additional five-year
    period. Our manufacturing facility is subject to periodic inspections by the FDA and foreign equivalents to ensure that it is operating in compliance with current Good Manufacturing Practices, or cGMP, requirements. We have begun work on a new
    manufacturing facility in Oceanside, California that will expand our manufacturing capacity to support our advancing pipeline. Refer to Part I, Item 2, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Properties</span>,
    for further discussion of this lease facility.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As part of our collaborations, we may agree to manufacture clinical trial material and/or commercial drug supply for our partners. For
    example, in the past we have manufactured clinical trial material for AstraZeneca, Biogen, GSK and Novartis and commercial drug supply for Biogen.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe we have sufficient manufacturing capacity at our own facility or at contract manufacturing organizations, or CMOs, to meet our
    current internal research, development and potential commercial needs, as well as our obligations under existing agreements with our partners for research, development and commercial material. We manufacture process performance qualification batches
    and pre-approval inspection batches of our Phase 3 medicines that may be used for regulatory submissions and, pending regulatory approval, commercial sale. We believe our current network of CMO partners are capable of providing sufficient quantities to
    meet anticipated commercial demands. Additionally, we continue to evaluate relationships with additional suppliers to increase overall capacity and diversify our supply chain. While we believe that there are alternate sources of supply that can satisfy
    our commercial requirements, it is possible that identifying and establishing relationships with such sources, if necessary, could result in significant delay or material additional costs. We also could experience a disruption in supply from our
    current CMO partners.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CMOs are subject to the FDA&#8217;s cGMP requirements and other rules and regulations prescribed by foreign regulatory authorities. We depend on
    our CMO partners for continued compliance with cGMP requirements and applicable foreign standards.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Specifically, we have the following in place for our approved medicines, SPINRAZA, TEGSEDI and WAYLIVRA and our medicines in Phase 3
    development.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is responsible for SPINRAZA drug supply.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">TEGSEDI and WAYLIVRA</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For TEGSEDI&#8217;s commercial drug supply, we are using CMOs to produce custom raw materials, API and finished goods. For WAYLIVRA&#8217;s commercial
    drug supply, we have manufactured custom raw materials and API. We are using CMOs to produce the finished goods for WAYLIVRA. Our CMO partners have extensive technical expertise and cGMP experience. We believe we and our current network of CMO partners
    are capable of manufacturing sufficient quantities to meet anticipated commercial demands.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our CMO partner supplied the API and the finished drug product for eplontersen&#8217;s Phase 3 program. Pursuant to our collaboration with
    AstraZeneca, we will manufacture and supply eplontersen through a CMO for the ongoing clinical trials, process performance qualification batches and pre-approval inspection batches. AstraZeneca is responsible for commercial drug supply.</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Olezarsen, Donidalorsen, ION363</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We and/or the CMOs have supplied the API and the finished
      drug product for </span>olezarsen, donidalorsen and ION363 that we believe will be <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">sufficient through the completion of the Phase 3 programs for each medicine, including
      process performance qualification batches and pre-approval inspection batches. We plan to leverage our relationships with CMOs to procure long-term raw material and drug supply at competitive prices in the future.</span></div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Tofersen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen is responsible for tofersen drug supply, including launch supplies.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We supplied the API and the finished drug product for pelacarsen&#8217;s Phase 3 program. Pursuant to our collaboration with Novartis, Novartis
    is responsible for any further pelacarsen drug supply.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patents and Proprietary Rights</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends, in part, on our ability to obtain patent protection for our products in the U.S. and other countries. We own or have
    exclusively licensed a substantial patent estate with numerous issued patents worldwide protecting our products and, more generally, our platform for development and commercialization of RNA-targeting therapeutics. We focus our resources on patents and
    new patent applications that drive value for our company.</div>

  <div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We own or control patents that provide exclusivity for products in our pipeline and patents that provide exclusivity for our core
    technology in the field of oligonucleotides and RNA-targeting therapeutics more generally. Our core technology patents include claims to chemically modified oligonucleotides as well as medicine designs utilizing these chemical modifications. These core
    claims are independent of specific therapeutic target, nucleic acid sequence, or clinical indication. We also own a large number of patents claiming oligonucleotide compounds having nucleic acid sequences complementary to therapeutic target nucleic
    acids, independent of the particular chemical modifications incorporated into the oligonucleotide compound. Importantly, we seek and obtain issued patent claims to specifically protect each of our medicines. For example, we file and seek to obtain
    claims covering each drug&#8217;s nucleic acid sequence and precise drug design. In sum, we maintain our competitive advantage in the field of oligonucleotide therapeutics technology by protecting our core platform technology and by creating multiple layers
    of patent protection for each of our specific medicines in development.</div>

  <div><br />
  </div>

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    <td style="width: 75.89%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Type of Patent Claim</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Broadly Applicable to Specific)</div>
        </td>

    <td style="width: 0.81%; vertical-align: top;">&#160;</td>

    <td style="width: 23.29%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 75.89%; vertical-align: top;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Chemically Modified Nucleosides and Oligonucleotides (target and sequence independent)</span></div>
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Drug Design Motifs (target and sequence independent)</span></div>
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">LIgand-Conjugated Antisense (LICA) Technology</span></div>
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Therapeutic Methods (sequence and chemistry independent)</span></div>
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Oligonucleotide Sequence (chemistry independent)</span></div>
          <div style="text-align: left; text-indent: -18pt; margin-left: 52.8pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#9679;</span><span class="TRGRRTFtoHTMLTab" style="display: inline-block; text-indent: 0px; font-size: 1px; width: 18pt">&#160;</span><span style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug Composition</span></div>
        </td>

    <td style="width: 0.81%; vertical-align: top;">&#160;</td>

    <td style="width: 23.29%; vertical-align: top;">
          <div style="text-align: left;"><img width="115" height="129" src="image7.jpg" alt="graphic" /></div>
        </td>

  </tr>


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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Chemically Modified Nucleosides and Oligonucleotides</span></div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The most broadly applicable of our patents are those that claim modified nucleosides and oligonucleotides comprising the modified
    nucleosides that we incorporate into our medicines to increase their therapeutic efficacy. Nucleosides and chemically modified nucleosides are the basic building blocks of our medicines. Therefore, claims that cover any oligonucleotide incorporating
    one of our proprietary modified nucleosides can apply to a wide array of therapeutic mechanisms of action as well as several therapeutic targets. The following are some of our patents in this category in key jurisdictions (U.S., Europe and Japan):</div>

  <div><br />
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,399,845</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,741,457</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,022,193</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides containing cEt nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1984381</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2314594</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides containing cEt nucleoside analogs and methods of use</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Japan</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5342881</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cEt nucleosides and oligonucleotides containing these nucleoside analogs</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,569,686</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR SYNTHESIS OF BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of synthesizing cEt nucleosides</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Drug Design Motifs</span></div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have patents that claim oligonucleotides comprising drug design motifs, or patterns of nucleoside modifications at specified
    positions in an oligonucleotide. Patent claims covering drug design motifs are independent of nucleic acid sequence, so they cover oligonucleotides having the recited motif, regardless of cellular target or clinical indication. The claimed motifs
    generally confer properties that optimize oligonucleotides for a particular mechanism of action, such as ribonuclease H (RNase H), RNAi, or splicing. We have designed oligonucleotides incorporating motifs, which we refer to as chimeric compounds or
    gapmers, to exploit the RNase H mechanism to achieve target RNA reduction. We have patent claims to such antisense drug design motifs incorporating bicyclic nucleosides, which include both locked nucleic acids, or &#8220;LNA&#8221; and cEt. The following patents
    are some examples of our issued patents in this category in key jurisdictions (U.S., Europe and Japan):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,750,131</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5&#8217;-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides having 5&#8217;-methyl BNA nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2092065</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having 2&#8217;-modifed and LNA nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410053</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2410054</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having a 2&#8217;-modifed nucleoside in the 5&#8217;-wing and a bicyclic nucleoside in the 3&#8217;-wing</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Japan</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5665317</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having wings comprised of 2&#8217;-MOE and bicyclic nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,550,988</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,493,092</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ANTISENSE COMPOUNDS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2028</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having BNA nucleosides and 2&#8217;-MOE nucleosides and/or 2&#8217;-OMe nucleosides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3067421</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">OLIGOMERIC COMPOUNDS COMPRISING BICYCLIC NUCLEOTIDES AND USES THEREOF</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gapmer oligonucleotides having at least one bicyclic, one 2&#8217;-modified nucleoside and one 2&#8217;-deoxynucleoside</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">LIgand-Conjugated Antisense (LICA) Technology</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have patent claims to new chemistries created to enhance targeting of antisense medicines to specific tissues and cells to improve
    a drug&#8217;s properties. We designed our GalNAc LICA medicines to provide an increase in potency for targets in the liver. We have successfully obtained issued patent claims covering our LICA technology conjugated to any modified oligonucleotide, including
    gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides. The following patents are some examples of our issued patents in this category:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,127,276</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,549</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA conjugate having our preferred linker and cleavable moiety conjugated to any oligomeric compound or any nucleoside having a 2&#8217;-MOE
            modification or a cEt modification</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991661</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Preferred THA LICA conjugated to any group of nucleosides, including gapmers, double-stranded siRNA compounds, and fully modified oligonucleotides</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Therapeutic Methods of Treatment and Oligonucleotide Drug Sequences</span></div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our broad core patents, we also own hundreds of patents, worldwide, with claims to antisense compounds having particular
    sequences and compounds directed to particular therapeutically important targets or methods of achieving cellular or clinical endpoints using these antisense compounds. These &#8220;Target&#8221; patents also include claims reciting the specific nucleic acid
    sequences utilized by our products, independent of chemical modifications and motifs. In addition, our product-specific patents typically include claims combining specific nucleic acid sequences with nucleoside modifications and motifs. In this way, we
    seek patent claims narrowly tailored to protect our products specifically, in addition to the broader core antisense patents described above.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">SPINRAZA and Survival Motor Neuron</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe SPINRAZA is protected from generic competition in the U.S. until at least 2035 and in Europe until at least 2030 by a suite of
    patents. These issued patents include: (i) patents licensed from the University of Massachusetts drawn to antisense compounds having the sequence of SPINRAZA, independent of chemical modification and uses of such compounds for treating SMA, and (ii)
    joint patents with Cold Spring Harbor Laboratory claiming fully modified 2&#8217;MOE compositions targeting SMN2, including the precise composition of matter of SPINRAZA and methods of using such compositions. We have filed for patent term extension, to
    potentially extend the term beyond 2030. With Biogen&#8217;s license of SPINRAZA, we assigned our interest in these patents to Biogen. The table below lists some key issued patents protecting SPINRAZA in the U.S. and Europe:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,266,822</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of increasing exon-7 containing SMN2 mRNA in a cell using an oligonucleotide having the sequence of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,110,560</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using antisense oligonucleotides having sequence of SPINRAZA to alter splicing of SMN2 and/or to treat SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1910395</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3308788</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,838,657</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINAL MUSCULAR ATROPHY (SMA) TREATMENT VIA TARGETING OF SMN2 SPLICE SITE INHIBITORY SEQUENCES</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides having sequence of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,361,977</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sequence and chemistry (full 2&#8217;-MOE) of SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,980,853</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,717,750</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of administering SPINRAZA to a patient</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3449926</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pharmaceutical compositions that include SPINRAZA for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3305302</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2030</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds including SPINRAZA for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,926,559</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATION OF SMN2 SPLICING IN A SUBJECT</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA doses for treating SMA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,436,802</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR TREATING SPINAL MUSCULAR ATROPHY</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA dosing regimen for treating SMA</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">TEGSEDI and Transthyretin</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe TEGSEDI is protected from generic competition in the U.S. and Europe until at least 2031. Additional patent applications
    designed to protect TEGSEDI in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting TEGSEDI<sub>&#160;</sub>in the U.S. and Europe:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,101,743</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2025</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,697,860</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">DIAGNOSIS AND TREATMENT OF DISEASE</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,061,044</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Sodium salt composition of TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,399,774</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating transthyretin amyloidosis by administering TEGSEDI</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2563920</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF TRANSTHYRETIN EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2031</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of TEGSEDI</div>
        </td>

  </tr>


</table>
  <div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">WAYLIVRA and Apolipoprotein C-III</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have obtained patent claims in the U.S. and Europe drawn to the use of antisense compounds complementary to a broad active region of
    human ApoC-III, including the site targeted by WAYLIVRA. We have also obtained issued patents claiming the specific sequence and chemical composition of WAYLIVRA in the U.S. and Europe. We believe the issued claims protect WAYLIVRA from generic
    competition in the U.S. and Europe until at least 2023 and 2024, respectively. The table below lists some key issued patents protecting WAYLIVRA in the U.S. and Europe:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,624,496</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,598,227</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating hyperlipidemia, lowering cholesterol levels or lowering triglyceride levels with WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,750,141</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1622597</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense sequence and chemistry of WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2441449</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Antisense compounds specifically hybridizable within the nucleotide region of ApoCIII targeted by WAYLIVRA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3002007</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2024</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Compounds complementary to an ApoCIII nucleic acid for use in therapy</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,157,082</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of using ApoCIII antisense oligonucleotides for reducing pancreatitis and chylomicronemia and increasing HDL</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,593,333</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating lipoprotein lipase deficiency with an ApoCIII specific inhibitor wherein triglyceride levels are reduced</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2956176</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">MODULATION OF APOLIPOPROTEIN C-III (APOCIII) EXPRESSION IN LIPOPROTEIN LIPASE DEFICIENT (LPLD) POPULATIONS</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ApoCIII specific inhibitors including WAYLIVRA for treating lipoprotein lipase deficiency or FCS</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">and
      Transthyretin</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We believe eplontersen is protected from generic competition
      in the U.S. and Europe until at least 2034. Additional patent applications to protect eplontersen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting </span>eplontersen <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in the U.S. and Europe:</span></div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,683,499</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of eplontersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3524680</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING TTR EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of eplontersen</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Olezarsen and ApoC-III</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe olezarsen is protected from generic competition in the U.S. and Europe until at least 2034. Additional patent applications to
    protect olezarsen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting olezarsen in the U.S. and Europe.</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,163,239</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of olezarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2991656</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN C-III EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of olezarsen</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Donidalorsen and PKK</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe donidalorsen is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications
    to protect donidalorsen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting donidalorsen in the U.S. and Europe.</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">United States</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,315,811</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating HAE</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2717923</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS FOR MODULATING KALLIKREIN (KLKB1) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2032</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Compounds for use in treating an inflammatory condition, including HAE</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,294,477</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of donidalorsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3137091</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING PKK EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of donidalorsen</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">ION363 and FUS</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent applications designed to protect ION363 from generic competition are being pursued in the U.S. and Europe. Patents issued from
    these applications would have terms until at least 2040. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The table below lists some key pending patent applications designed to protect ION363</span> in the U.S. and Europe:</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Jurisdiction</span></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17/613,183</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of ION363</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20815459.1</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOUNDS AND METHODS FOR REDUCING FUS EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2040</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of ION363</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Tofersen and SOD-1</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe tofersen is protected from generic competition in the U.S. and Europe until at least 2035. Additional patent applications
    designed to protect tofersen in other foreign jurisdictions are being pursued. With Biogen&#8217;s license of tofersen, we assigned our interest in these patents to Biogen. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The
      table below lists some key issued patents protecting t</span>ofersen in the U.S. and Europe:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,385,341</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tofersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,669,546</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating a SOD-1 associated neurodegenerative disorder by administering tofersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,968,453</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Methods of treating a SOD-1 associated neurodegenerative disorder by administering a pharmaceutical composition of tofersen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3126499</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS FOR MODULATING SOD-1 EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2035</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of tofersen</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Pelacarsen and Apo(a)</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe pelacarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> is protected from generic competition
      in the U.S. and Europe until at least 2034. Additional patent protection designed to protect pelacarsen in other foreign jurisdictions are being pursued. The table below lists some key issued patents protecting </span>pelacarsen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in the U.S. and Europe:</span></div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 16.86%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Jurisdiction</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 11.11%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Patent No.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 26.96%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.82%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Expiration</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 25.58%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Claims</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,574,193</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of lowering Apo(a) and/or Lp(a) levels with an oligonucleotide
              complementary within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,478,448</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Methods of treating hyperlipidemia with an oligonucleotide complementary
              within the nucleotide region of Apo(a) targeted by p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,884,072</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2855500</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">METHODS AND COMPOSITIONS FOR MODULATING APOLIPOPROTEIN (A) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2033</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oligonucleotides complementary within the nucleotide region of Apo(a) targeted by pelacarsen for decreasing Apo(a) expression</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
          <div>&#160;</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,181,550</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Composition of p</span>elacarsen</div>
        </td>

  </tr>

  <tr>

    <td style="width: 16.86%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Europe</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 11.11%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2992009</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 26.96%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">COMPOSITIONS AND METHODS FOR MODULATING APOLIPOPROTEIN (a) EXPRESSION</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.82%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2034</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 25.58%; vertical-align: top; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Composition of pelacarsen</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We seek patent protection in significant markets and/or countries for each medicine in development. We also seek to maximize patent term.
    In some cases, the patent term can be extended to recapture a portion of the term lost during FDA regulatory review. The patent exclusivity period for a medicine will prevent generic medicines from entering the market. Patent exclusivity depends on a
    number of factors including initial patent term and available patent term extensions based upon delays caused by the regulatory approval process.</div>

  <div><br />
  </div>

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  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Manufacturing Patents</span></div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also own patents claiming methods of manufacturing and purifying oligonucleotides. These patents claim methods for improving
    oligonucleotide drug manufacturing, including processes for large-scale oligonucleotide synthesis and purification. These methods allow us to manufacture oligonucleotides at lower cost by, for example, eliminating expensive manufacturing steps.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also rely on trade secrets, proprietary know-how and continuing technological innovation to develop and maintain a competitive position
    in antisense therapeutics.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Government Regulation</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 35pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Regulation by government authorities in the U.S. and other countries is a significant component in the development, manufacture and
    commercialization of pharmaceutical products and services. In addition to regulations enforced by the FDA and relevant foreign regulatory authorities, we are also subject to regulation under the Occupational Safety and Health Act, the Environmental
    Protection Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act and other present and potential future federal, state and local regulations.</div>

  <div style="text-align: justify; text-indent: 35pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Extensive regulation by the U.S. and foreign governmental authorities governs the development, manufacture and sale of our medicines. In
    particular, our medicines are subject to a number of approval requirements by the FDA in the U.S. under the Federal Food, Drug and Cosmetic Act, or FDCA, and other laws and by comparable agencies in those foreign countries in which we conduct business.
    The FDCA and other various federal, state and foreign statutes govern or influence the research, testing, manufacture, safety, labeling, storage, recordkeeping, approval, promotion, marketing, distribution, post-approval monitoring and reporting,
    sampling, quality, and import and export of our medicines. State, local, and other authorities also regulate pharmaceutical manufacturing facilities and procedures.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing facility and our CMOs are subject to periodic inspection by the FDA and other foreign equivalents to ensure that they
    are operating in compliance with cGMP requirements. In addition, marketing authorization for each new medicine may require a rigorous manufacturing pre-approval inspection by regulatory authorities. Post approval, there are strict regulations regarding
    changes to the manufacturing process, and, depending on the significance of the change, changes may require prior FDA approval. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation
    requirements upon us and any third-party manufacturers that we may decide to use.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA must approve any new medicine before a manufacturer can market it in the U.S. In order to obtain approval, we and our partners
    must complete clinical studies and prepare and submit an NDA to the FDA. If the FDA approves a medicine, it will issue an approval letter authorizing commercial marketing of the medicine and may require a risk evaluation and mitigation strategy, or
    REMS, to help ensure the benefits of the medicine outweigh the potential risks. For example, TEGSEDI has a REMS program. The requirements for REMS can materially affect the potential market and profitability of our medicines. In foreign jurisdictions,
    the drug approval process is similarly demanding.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For any approved medicine, domestic and foreign sales of the medicine depend, in part, on the availability and amount of coverage and
    adequate reimbursement by third-party payers, including governments and private health plans. The process for determining whether a payer will provide coverage for a product may be separate from the process for setting the reimbursement rate that the
    payer will pay for the product, or procedures which utilize such product. Private health plans may seek to manage cost and use of our medicines by implementing coverage and reimbursement limitations. For example, third-party payers may limit coverage
    to specific products on an approved list, or formulary, which might not include all U.S. FDA-approved products for a particular indication. In certain jurisdictions, governments may also regulate or influence coverage, reimbursement and/or pricing of
    our medicines to control cost or affect use. Within the EU a variety of payers pay for medicines, with governments being the primary source of payment. Negotiating pricing with governmental authorities can delay commercialization. Such pricing and
    reimbursement factors could impact our ability and that of our commercial partners to successfully commercialize approved medicines. Further, it is possible that additional governmental action is taken in response to the COVID-19 pandemic.</div>

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  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Both the federal and state governments in the U.S. and foreign governments continue to propose and pass new legislation and regulations
    designed to contain or reduce the cost of healthcare. For example, in July 2021, the Biden administration released an executive order, &#8220;Promoting Competition in the American Economy,&#8221; with multiple provisions aimed at prescription drugs. In response to
    Biden&#8217;s executive order, on September 9, 2021, the U.S. Department of Health and Human Services, or HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential
    legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles. No legislation or administrative actions have been finalized to implement these principles. Congress is also
    considering additional health reform measures that may result in decreased reimbursement, which may further exacerbate industry-wide pressure to reduce the prices charged for medical products.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There has also been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which
    has resulted in efforts to bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for medicines. For example, in August 2022,
    President Biden signed the Inflation Reduction Act of 2022, or the IRA, into law, which includes key actions aimed at reducing the costs of prescription drugs and allows HHS to negotiate the price of certain single-source drugs covered under Medicare
    and establish a price cap on such drugs, known as the Maximum Fair Price. It is currently unclear how the IRA will be effectuated but it is likely to have a significant impact on the pharmaceutical industry. There are important exemptions to the
    Maximum Fair Price, including for medications that are orphan drug designated and approved for only one rare disease, and drugs with low Medicare spend as defined by the Centers for Medicare &amp; Medicaid Services.&#160; In an effort to curb Medicare
    patients&#8217; out-of-pocket costs for prescription drugs, the Part D redesign legislation requires manufacturers to contribute to the catastrophic coverage phase for Part D drugs as discounts through a manufacturer discount program. Furthermore, any
    reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private payers.&#160; Our future product sales may be subject to additional discounts from list price in the form of rebates and
    discounts provided to 340B covered entities. Changes to the 340B program or to Medicare or Medicaid programs at the federal or state level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, the distribution of prescription pharmaceutical products is subject to the Drug Supply Chain Security Act, or DSCA, which
    regulates the distribution and tracing of prescription drugs and prescription drug samples at the federal level and sets minimum standards for the regulation of drug distributors by the states. The DSCA imposes requirements to ensure accountability in
    distribution and to identify and remove counterfeit and other illegitimate products from the market.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other healthcare laws that may affect our ability to operate include, for example, the following:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act,
            which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign and state laws governing the privacy and security of health information, such as the General Data Protection Regulation, or GDPR, in the EU; and the California
            Consumer Privacy Act, or CCPA, in California, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect; and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Physician Payments Sunshine Act, which requires manufacturers of medicines, devices, biologics, and medical supplies to report annually to the HHS information related
            to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), other healthcare providers (such as physician assistants and nurse practitioners), and teaching
            hospitals, and ownership and investment interests held by physicians and their immediate family members.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Sales and Marketing</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Numerous regulatory authorities in addition to the FDA, including, in the U.S., the Centers for Medicare and Medicaid Services, other
    divisions of the HHS, the U.S. Department of Justice, and similar foreign, state and local government authorities, regulate sales, promotion and other activities following drug approval. As described above, the FDA regulates all advertising and
    promotion activities for drugs under its jurisdiction both prior to and after approval. Only those claims relating to safety and efficacy that the FDA has approved may be used in labeling. Physicians may prescribe legally available drugs for uses that
    are not described in the drug&#8217;s labeling and that differ from those we tested and the FDA approved. Such off-label uses are common across medical specialties and often reflect a physician&#8217;s belief that the off-label use is the best treatment for the
    patients. The FDA does not regulate the behavior of physicians in their choice of treatments, but FDA regulations do impose stringent restrictions on manufacturers&#8217; communications regarding off-label uses. If we do not comply with applicable FDA
    requirements, we may face adverse publicity, enforcement action by the FDA, corrective advertising, consent decrees and the full range of civil and criminal penalties available to the FDA. Promotion of off-label uses of drugs can also implicate the
    false claims laws described below.</div>

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  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S. sales, marketing and scientific/educational programs must also comply with various federal and state laws pertaining to
    healthcare &#8220;fraud and abuse,&#8221; including anti-kickback laws and false claims laws. Anti-kickback laws make it illegal for a prescription drug manufacturer to solicit, offer, receive, or pay any remuneration in exchange for, or to induce, the referral of
    business, including the purchase or prescription of a particular drug. Due to the breadth of the statutory provisions, limited statutory exceptions and regulatory safe harbors, and the absence of guidance in the form of regulations and very few court
    decisions addressing industry practices, it is possible that our practices might be challenged under anti-kickback or similar laws. Moreover, recent healthcare reform legislation has strengthened these laws. For example, the Patient Protection and
    Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, or Affordable Care Act, among other things, amends the intent requirement of the federal anti-kickback and criminal healthcare fraud statutes to clarify that a
    person or entity does not need to have actual knowledge of this statute or specific intent to violate it. In addition, the Affordable Care Act clarifies that the government may assert that a claim that includes items or services resulting from a
    violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes. False claims laws prohibit anyone from knowingly and willingly presenting, or causing to be presented for payment, to
    third-party payers (including Medicare and Medicaid) claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed, or claims for medically unnecessary items or services. Our activities
    relating to the sale and marketing of our drugs may be subject to scrutiny under these laws. Violations of fraud and abuse laws may be punishable by criminal and civil sanctions, including fines and civil monetary penalties, the possibility of
    exclusion from federal healthcare programs (including Medicare and Medicaid) and corporate integrity agreements, which impose, among other things, rigorous operational and monitoring requirements on companies. Similar sanctions and penalties also can
    be imposed upon executive officers and employees, including criminal sanctions against executive officers under the so-called &#8220;responsible corporate officer&#8221; doctrine, even in situations where the executive officer did not intend to violate the law and
    was unaware of any wrongdoing.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Given the significant penalties and fines that can be imposed on companies and individuals if convicted, allegations of such violations
    often result in settlements even if the company or individual being investigated admits no wrongdoing. Settlements often include significant civil sanctions, including fines and civil monetary penalties, and corporate integrity agreements. If the
    government were to allege or convict us or our executive officers of violating these laws, our business could be harmed. In addition, private individuals can bring similar actions. Our activities could be subject to challenge for the reasons discussed
    above and due to the broad scope of these laws and the increasing attention being given to them by law enforcement authorities. Other healthcare laws that may affect our ability to operate include HIPAA, which prohibits, among other things, executing
    or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, also governs the conduct
    of certain electronic healthcare transactions and protects the security and privacy of protected health information; analogous state laws governing the privacy and security of health information, some of which are more stringent than HIPAA and many of
    which differ from each other in significant ways and may not have the same effect, and the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to the HHS information
    related to payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members. Further, there are an increasing number of
    state laws that require manufacturers to make reports to states on pricing and marketing information. Many of these laws contain ambiguities as to what is required to comply with the laws. Given the lack of clarity in laws and their implementation, our
    reporting actions could be subject to the penalty provisions of the pertinent state authorities.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 40.8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Similar rigid restrictions are imposed on the promotion and marketing of drugs in the E.U. and other countries. Even in those countries
    where we may not be directly responsible for the promotion and marketing of our medicines, if our potential international distribution partners engage in inappropriate activity, it can have adverse implications for us.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The U.S. Foreign Corrupt Practices Act, or FCPA, prohibits certain individuals and entities, including us, from promising, paying,
    offering to pay, or authorizing the payment of anything of value to any foreign government official, directly or indirectly, to obtain or retain business or an improper advantage. If we violate the FCPA, it could result in large civil and criminal
    penalties as well as an adverse effect on our reputation, operations, and financial condition. We could also face collateral consequences such as debarment and the loss of export privileges.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Competition</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Our Business in General</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Some of our medicines may compete with existing therapies for market share and some of our medicines in development may compete for
    patients in clinical trials. In addition, there are a number of companies pursuing the development of genetic medicines and the development of pharmaceuticals utilizing these technologies. These companies include biopharmaceutical companies and large
    pharmaceutical companies acting either independently or together. Our medicines are differentiated from traditional small molecule medicines by their chemistry, how they move in the body, how they act in the body, delivery technology, and formulations.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our approved medicines and our medicines under development address numerous markets. The diseases our medicines target for which we have
    or may receive marketing authorization will determine our competition. For some of our medicines, an important factor may be the timing of market introduction of competitive products. Accordingly, the relative speed with which we can develop medicines,
    complete the clinical trials and marketing authorization processes and supply commercial quantities of the medicines to the market are important competitive factors. We expect to compete with products approved for sale based on a variety of factors,
    including, among other things, product efficacy, safety, mechanism of action, dosing administration, marketing and sales strategy and tactics, availability, price, and reimbursement.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Below we have included what we believe to be medicines that compete or may compete directly with our marketed medicines and the medicines
    we currently have in Phase 3 trials. We included competitors, potential competitors that are past Phase 1 development or potential competitors that plan to start a pivotal study this year.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We do not believe that any medicines meet these criteria to compete with ION363.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider the following medicines as competitors to SPINRAZA for the indication of SMA:</div>

  <div><br />
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Zolgensma</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Onasemnogene abeparvovec)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Gene therapy targeting the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for pediatric SMA patients less than 2 years of age</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Evrysdi</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Risdiplam)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Roche</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule medicine that modulates splicing of the SMN2 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for SMA in pediatric and adult patients</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

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</table>
  <div><br />
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">TEGSEDI and Eplontersen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider the following medicines as competitors and potential future competitors to TEGSEDI and eplontersen for the indication of hATTR
    amyloidosis and/or ATTR cardiomyopathy:</div>

  <div><br />
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onpattro</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Patisiran)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An RNAi medicine formulated with lipid nanoparticles to inhibit TTR mRNA</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved ATTRv-PN/</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Submitted in the U.S. for ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vyndaqel/Vyndamax</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Tafamidis and tafamidis meglumine)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pfizer</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A small molecule medicine to stabilize TTR protein</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in EU, Japan and select other markets for ATTRv-PN;</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved in U.S., EU, Japan and select other markets for ATTR-CM; indications vary by region</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amvuttra</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Vutrisiran)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Alnylam</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An RNAi medicine conjugated with GalNAc to inhibit TTR mRNA</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for ATTRv-PN in the U.S., Submitted in the EU for ATTRv-PN, Phase 3 for ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acoramidis</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BridgeBio</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Small molecule that binds and stabilizes TTR in the blood</div>
        </td>

    <td style="width: 2.42%; vertical-align: middle; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 ATTR-CM</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">WAYLIVRA and Olezarsen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with WAYLIVRA and olezarsen in FCS and SHTG:</div>

  <div><br />
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

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    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Arrowhead Pharmaceuticals</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Targets APOCIII by utilizing Targeted RNAi Molecule Platform</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3 FCS,</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 SHTG</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lomitapide</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amryt Pharma</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Microsomal triglyceride transfer protein (MTP) inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 FCS (investigator led)</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pegozafermin</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89bio</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">FGF21 analog</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2 SHTG</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>


</table>
  <div><br />
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Donidalorsen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with donidalorsen as a prophylactic treatment for patients with HAE:</div>

  <div><br />
  </div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takhzyro</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(lanadelumab-flyo)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takeda</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A monoclonal antibody that inhibits plasma kallikrein activity</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients 12 years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cinryze</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(C1 esterase inhibitor)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Takeda</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A human plasma protein that mediates inflammation and coagulation</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients six years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Orladeyo</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(berotralstat)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BioCryst</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral plasma kallikrein inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients 12 years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Oral</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Haegarda</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(C1 esterase inhibitor)</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CSL Behring</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C1 esterase inhibitor</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Approved for HAE patients six years and older</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">garadacimab</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CSL Behring</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An anti-factor XIIa monoclonal antibody</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NTLA-2002</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intellia</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">CRISPR therapeutic candidate designed to inactivate the kallikrein B1 gene</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 1/2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

  </tr>


</table>
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  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Pelacarsen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicines could compete with pelacarsen in CVD in patients with elevated LP(a):</div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olpasiran</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amgen/ Arrowhead Pharmaceuticals</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic designed to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 3</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>

  <tr>

    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SLN360</div>
        </td>

    <td style="width: 1.67%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Silence Therapeutics</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RNAi therapeutic designed to lower Lp(a)</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(255, 255, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(255, 255, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Subcutaneous Injection</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

  </tr>


</table>
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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Tofersen</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that the following medicine could compete with tofersen in SOD1-ALS:</div>

  <div><br />
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    <td style="width: 18.07%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Medicine</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 12.15%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Company</div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 22.53%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Medicine Description</span><sup> (1)</sup></div>
        </td>

    <td style="width: 2.42%; vertical-align: bottom;">&#160;</td>

    <td style="width: 20.85%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Phase</span><sup> (1)</sup></div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 18.24%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Route of Administration</span><sup> (1)</sup></div>
        </td>

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    <td style="width: 18.07%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NI-204</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.15%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Neurimmune</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 22.53%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A human derived antibody targeting misfolded SOD1</div>
        </td>

    <td style="width: 2.42%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>

    <td style="width: 20.85%; vertical-align: middle; background-color: rgb(204, 238, 255);">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Phase 2</div>
        </td>

    <td style="width: 1.67%; vertical-align: middle; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 18.24%; vertical-align: middle; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intravenous Infusion</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 8pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 8pt;">Taken from public documents including respective company press releases, company presentations, and scientific presentations.</div>
        </td>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">ION363</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe there is no medicine in clinical development for FUS-ALS.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Environmental, Social and Governance Initiatives</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize the importance of Environmental, Social and Governance, or ESG, initiatives as it relates to our business strategy and risk
    assessment. During 2021 and 2022, we took steps to formalize our corporate responsibility program and capture and report on the impact of our ESG efforts. In December 2022, we issued our latest corporate responsibility report. As part of our ongoing
    work, we identified the following corporate responsibility initiatives that we believe are most important to our business:</div>

  <div><br />
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Safety of patients in clinical trials;</div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Product quality and safety and supply chain management;</div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Access to medicines and tackling untreatable diseases;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Environmental sustainability;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Human resource management;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diversity, equity and inclusion;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee health and safety; and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Governance and business ethics</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We continue to build our corporate responsibility program and ESG framework to support our ongoing commitment to operate our business
    responsibly and sustainably. In 2022, we established a formal Corporate Responsibility Steering Committee, or Committee, to ensure we develop the right programs and policies to continue to integrate ESG across our organization. Our corporate
    responsibility initiatives, policies and programs are reviewed on a regular basis by the Committee and its recommendations are key to driving efforts to advance our corporate responsibility strategy to support our growth.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Committee reports to our Chief Executive Officer and consists of senior leaders in key functions across the company, including legal,
    finance, human resources and corporate affairs. The Committee is now part of our governance framework, which defines responsibilities and ensures we have the right systems and controls to oversee ethical and sustainable operations across our business.
    The Committee periodically updates our executive leadership and the appropriate committees of our Board of Directors on our ongoing ESG efforts.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We look to our stakeholders and third-party frameworks such as the Sustainability Accounting Standards Board Health Care &#8211; Biotechnology
    and Pharmaceuticals Standard and the Task Force on Climate-Related Financial Disclosures to inform our approach and our disclosures.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We encourage you to view our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2022
      Corporate Responsibility Report</span> published on our website for more detailed information regarding our ESG initiatives. Nothing in the report or on our website shall be deemed incorporated by reference into this Annual Report on Form 10-K.</div>

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  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Employees &amp; Human Capital</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 16, 2023, we
    employed 796 people, the vast majority of whom reside in the U.S. A significant number of our management and professional employees have had prior experience with pharmaceutical, biotechnology or medical product companies. Our average employee turnover
    rate in 2022 was 13 percent, while the turnover for life sciences and medical device companies over this period was 23 percent according to a survey published by Radford &#8211; an Aon Hewitt Company. Given the uniqueness and complexity of our technology, it
    is critical to retain the knowledge and experience of outstanding long service employees. The experience and seniority of our employees is as critical to our future success as it has been to the success we have enjoyed to date.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collective bargaining agreements do not cover any of our employees, and management considers relations with our employees to be good. We
    believe that the future will be defined by outstanding people and we are committed to recruiting, developing, motivating, and rewarding them.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We encourage you to visit our website for more detailed information regarding our Human Capital programs and initiatives. Nothing on our
    website shall be deemed incorporated by reference into this Annual Report on Form 10-K.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Benefits</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reward our employees individually on the basis of their responsibilities and accomplishments. We offer competitive compensation and
    benefits to our employees. In addition to salary and bonus programs, we also offer:</div>

  <div><br />
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive medical, dental and vision insurance;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">401(k) matching;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock options, RSUs and an Employee Stock Purchase Plan, or ESPP;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vacation, holiday, sick time and paid time off for volunteering;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Wellness programs;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Flexible spending accounts for health and dependent day care needs;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Life, AD&amp;D insurance and long-term disability insurance coverage options; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Assistance Program, or EAP.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize achievements with salary increases, equity awards, promotions, and bonus opportunities.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Pay Equity</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are committed to paying our employees fairly, regardless of their gender, race, or other personal characteristics. To ensure we are
    achieving our commitment, we benchmark and evaluate pay based on market data and consider factors such as an employee&#8217;s role and experience, an employee&#8217;s performance and internal equity. We also regularly review our compensation practices, in terms of
    our overall workforce and individual employees, to ensure our pay is fair and equitable.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we engaged an independent third-party expert to perform a pay equity analysis that reviewed pay equity by gender, race and age.
    The results of this analysis did not reveal any pay gaps based on gender, race or age. We plan to continue to engage a third-party expert to review pay equity and report on this analysis as required by future reporting requirements. In 2022, we
    performed an internal analysis, leveraging our biostatistics team. The analysis showed similar results to the analysis performed in 2021. In addition, we are implementing a comprehensive plan to comply with the new California pay transparency law that
    went into effect on January 1, 2023.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Diversity, Equity and Inclusion</div>

  <div><br />
  </div>

  <div>
    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At Ionis, we encourage diversity in our workforce. Prejudicial barriers to human potential and productivity are foreign to our values.
      We recognize that for the full potential of our workforce to be realized, we must cultivate an inclusive culture where all employees feel empowered to contribute fully in an environment that values different perspectives, leading to better
      &#8203;&#8203;&#8203;&#8203;&#8203;&#8203;&#8203;ideas and increased innovation. We have several employee-led resource groups dedicated to different aspects of diversity and a diverse management team and board of directors.</div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Training and Development</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We designed our training and development programs to help employees gain important Ionis knowledge and develop the skills to be successful
    at Ionis. All of our trainings from new hire through senior leader, are focused on the Ionis culture and core principles and learning what we mean when we say: &#8220;Working the Ionis Way.&#8221;</div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40</div>

    </div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We empower our employees to build rewarding careers at Ionis, driven by a culture of having a bias to act that encourages personal and
    professional employee growth. Ionis offers robust training opportunities with course offerings and events available to every employee regardless of level or function. In addition, employees also have access to Ionis&#8217; learning and development library
    that houses important information on career growth and planning. By supporting our employees, we know that each professional development milestone enables our continued success.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Information about our Executive Officers</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following sets forth certain information regarding our executive officers as of February 16, 2023:</div>

  <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 25.83%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Name</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 8.33%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Age</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom;">&#160;</td>

    <td style="width: 62.5%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Position</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Executive Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph T. Baroldi</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Business Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. Frank Bennett, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Scientific Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onaiza Cadoret-Manier</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Global Product Strategy and Operations Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Richard S. Geary, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Development Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patrick R. O&#8217;Neil, Esq.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Chief Legal Officer, General Counsel and Corporate Secretary</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eugene Schneider, M.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Chief Clinical Development Officer</div>
        </td>

  </tr>

  <tr>

    <td style="width: 25.83%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eric E. Swayze, Ph.D.</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 8.33%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
        </td>

    <td style="width: 1.67%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 62.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Research</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">BRETT P. MONIA, Ph.D.</div>

  <div style="text-align: justify;"><span style="font-size: 8pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 38.15pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Monia was promoted to Chief Executive Officer in January 2020. From January 2018 to December 2019, Dr. Monia served as Chief
    Operating Officer. From January 2012 to January 2018, Dr. Monia served as Senior Vice President. From February 2009 to January 2012, Dr. Monia served as our Vice President, Drug Discovery and Corporate Development and from October 2000 to February
    2009, he served as our Vice President, Preclinical Drug Discovery. From October 1989 to October 2000 he held various positions within our Molecular Pharmacology department.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">JOSEPH T. BAROLDI</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Business Officer</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. Baroldi has served as Ionis&#8217; Executive Vice President, Chief Business Officer since January 2022. Prior to Ionis, Mr. Baroldi was the
    chief operating officer at Avidity Biosciences, a biotechnology company focused on oligonucleotide-based therapies. Prior to Avidity, Mr. Baroldi was Vice President, Business Development at Ionis, where he held several roles of increasing
    responsibility from 2009 to 2020. Mr. Baroldi has also held positions in strategic planning and scientific research for Gen-Probe Inc.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">C. FRANK BENNETT, Ph.D.</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Scientific Officer</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Bennett has served as Ionis&#8217; Executive Vice President, Chief Scientific Officer since April 2020. In January 2020, Dr. Bennett was
    promoted to Chief Scientific Officer. From January 2006 to December 2019, Dr. Bennett served as Senior Vice President, Antisense Research. From June 1995 to January 2006, Dr. Bennett served as our Vice President, Research. From March 1993 to June 1995,
    he was Director, Molecular Pharmacology, and from May 1992 to March 1993, he was an Associate Director in our Molecular and Cellular Biology department. Prior to joining Ionis in 1989, Dr. Bennett was employed by SmithKline and French Laboratories in
    various research positions. He is a member of the Board of Directors for Flamingo Therapeutics and an external member of the Hereditary Disease Foundation.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ONAIZA CADORET-MANIER</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Global Product Strategy and Operations Officer</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Ms. Cadoret-Manier has served as Ionis&#8217; Executive Vice
      President, Chief Product Strategy and Operations Officer since February 2022. From April 2020 to February 2022, Ms. Cadoret-Manier served as our Executive Vice President, </span>Chief Corporate Development and Commercial Officer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Ms. Cadoret-Manier joined Ionis as Chief Corporate Development and Commercial Officer in January 2020. Prior to joining Ionis, from 2018 to 2019 Ms. Cadoret-Manier was the chief
      commercial officer for Grail Biosciences, an early detection genomics company. Prior to Grail, Ms. Cadoret-Manier was vice president of the Respiratory Franchise at Genentech where she worked from 2011 to 2018. Ms. Cadoret-Manier also has held
      multiple senior management positions overseeing corporate strategy, alliances, and marketing and sales for numerous disease areas for Genentech, Pfizer and Amylin Pharmaceuticals.</span></div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">RICHARD S. GEARY, Ph.D.</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Development Officer</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Geary has served as Ionis&#8217; Executive Vice President, Chief Development Officer since January 2021. From April 2020 to December 2020,
    Dr. Geary served as our Executive Vice President, Development and from August 2008 to March 2020, was our Senior Vice President, Development. From August 2003 to August 2008, Dr. Geary served as our Vice President, Preclinical Development. From
    November 1995 to August 2003, he held various positions within the Preclinical Development department. Prior to joining Ionis in 1995, Dr. Geary was Senior Research Scientist and Group Leader for the bioanalytical and preclinical pharmacokinetics group
    in the Applied Chemistry Department at Southwest Research Institute.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ELIZABETH L. HOUGEN</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Finance and Chief Financial Officer</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ms. Hougen has served as Ionis&#8217; Executive Vice President and Chief Financial Officer since April 2020. From January 2013 to March 2020,
    Ms. Hougen served as our Senior Vice President, Finance and Chief Financial Officer. From January 2007 to December 2012, Ms. Hougen served as our Vice President, Finance and Chief Accounting Officer and from May 2000 to January 2007, she served as our
    Vice President, Finance. Prior to joining Ionis in 2000, Ms. Hougen was Executive Director, Finance and Chief Financial Officer for Molecular Biosystems, Inc., a public biotechnology company.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">PATRICK R. O&#8217;NEIL, Esq.</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
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  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Legal Officer, General Counsel and Corporate Secretary</div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mr. O&#8217;Neil has served as Ionis&#8217; Chief Legal Officer and General Counsel since September 2021. Mr. O&#8217;Neil also serves as our Corporate
    Secretary. From March 2020 to September 2021, Mr. O&#8217;Neil served as our Executive Vice President, Legal &amp; General Counsel and Chief Compliance Officer. From January 2013 to March 2020, Mr. O&#8217;Neil served as our Senior Vice President, Legal and
    General Counsel. From September 2010 to January 2013, Mr. O&#8217;Neil served as our Vice President, Legal and General Counsel and from January 2009 to September 2010, he served as our Vice President, Legal and Senior Transactions Counsel. From October 2001
    to January 2009 he held various positions within our Legal department. Prior to joining Ionis, Mr. O&#8217;Neil was an associate at Cooley LLP.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">EUGENE SCHNEIDER, M.D.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Chief Clinical Development Officer</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Schneider was promoted to Executive Vice President and Chief Clinical Development Officer of Ionis in January 2021. From August 2018
    to December 2020, Dr. Schneider served as our Senior Vice President, Head of Clinical Development. From April 2015 to July 2018, Dr. Schneider was our Vice President, Clinical Development, Severe and Rare Diseases. Dr. Schneider joined Ionis in
    December 2013 as Executive Director, Clinical Development. Dr. Schneider has two decades of experience in clinical development primarily in the rare diseases space. Prior to joining Ionis, Dr. Schneider was senior medical director at both Synageva
    BioPharma and Biovail Technologies Ltd.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ERIC E. SWAYZE, Ph.D.</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
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  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Executive Vice President, Research</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dr. Swayze has served as Ionis&#8217; Executive Vice President, Research since April 2020 and is responsible for leading preclinical antisense
      drug discovery and antisense technology research. In January 2020, Dr. Swayze was promoted to Senior Vice President of Research. Previously, Dr. Swayze was Vice President of Chemistry and Neuroscience Drug Discovery at Ionis, overseeing the
      advancement of multiple programs to clinical development. He joined Ionis in 1994 and has contributed to key technology advancements, including Ionis&#8217; Generation 2.5 chemistry and LICA technology.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Item 1A. RISK FACTORS</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Investing in our securities involves a high degree of risk. You should carefully consider the following information
    about the risks described below, together with the other information contained in this report and in our other public filings in evaluating our business. If any of the following risks actually occur, our business could be materially harmed, and our
    financial condition and results of operations could be materially and adversely affected. As a result, the trading price of our securities could decline, and you might lose all or part of your investment.</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Commercialization of our Medicines</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have limited experience as a company in commercializing medicines and we will have to invest significant resources to develop our
    capabilities. If we are unable to establish effective marketing, sales, market access, distribution, and related functions, or enter into agreements with third parties to commercialize our medicines, we may not be able to generate revenue from our
    medicines.</div>

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    <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We currently rely on third parties for the commercialization of our marketed medicines, have limited experience as a company in
      commercializing medicines and we will have to invest significant financial and management resources to develop the infrastructure required to successfully commercialize our medicines. There are significant risks involved in building and managing a
      sales organization, including our ability to hire, retain and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and
      marketing team. We will also need to scale-up existing internal support functions to aid our commercialization efforts, in particular, regulatory affairs and medical affairs. Any failure to effectively build or maintain the infrastructure required to
      successfully commercialize our medicines, including our sales, marketing, market access, distribution, and related capabilities, or scale-up our existing support functions, could adversely impact the revenue we generate from our medicines. In
      addition, if we choose to rely on third parties to assist us in commercializing our medicines, we may not be able to enter into collaborations or hire consultants or external service providers on acceptable financial terms, or at all. If we continue
      to engage third parties to assist us in the commercialization of our medicines, our product revenues and profitability may be lower than if we commercialized such medicines ourselves.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the market does not accept our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in
    development, we are not likely to generate substantial revenues or become consistently profitable.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Even if our medicines are authorized for marketing, our success will depend upon the medical community, patients and third-party payers
    accepting our medicines as medically useful, cost-effective, safe and convenient. Even when the FDA or foreign regulatory authorities authorize our or our partners&#8217; medicines for commercialization, doctors may not prescribe our medicines to treat
    patients. Furthermore, we and our partners may not successfully commercialize additional medicines.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Additionally, in many of the markets where we or our partners
      may sell our medicines in the future, if we or our partners cannot agree with the government or other third-party payers regarding the price we can charge for our medicines, we may not be able to sell our medicines in that market. Similarly, cost
      control initiatives by governments or third-party payers could decrease the price received for our medicines or increase patient coinsurance to a level that makes our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our
      medicines in development, economically unviable. </span>If the pricing of any of our medicines decreases for any reason, it will reduce our revenue for such medicine. For example, Biogen has disclosed that SPINRAZA revenue has decreased in part due
    to lower pricing in the U.S. and certain rest of world markets.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The degree of market acceptance for our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in
    development, depends upon a number of factors, including the:</div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">receipt and scope of marketing authorizations;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">establishment and demonstration in the medical and patient community of the efficacy and safety of our medicines and their potential advantages over competing products;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cost and effectiveness of our medicines compared to other available therapies;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">patient convenience of the dosing regimen for our medicines; and</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursement policies of government and third-party payers.</div>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Based on the profile of our medicines, physicians, patients, patient advocates, payers or the medical community in general may not accept
    or use any of the medicines that we may develop.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, TEGSEDI requires periodic blood and urine monitoring, is available in the U.S. only through a REMS program, and the product
    label in the U.S. has a boxed warning for thrombocytopenia and glomerulonephritis. Our main competitors in the U.S. market for TEGSEDI are patisiran and vutrisiran, both marketed by Alnylam Pharmaceuticals, Inc. Neither patisiran nor vutrisiran has a
    boxed warning nor does either require use of a REMS program. Additionally, the product label for WAYLIVRA in the European Union, or EU, requires regular blood monitoring. In each case, these label requirements have negatively affected our ability to
    attract and retain patients for these medicines. If we or our partner cannot effectively maintain patients on TEGSEDI or WAYLIVRA, including due to limitations or restrictions on the ability to conduct periodic blood and urine monitoring of our
    patients as a result of the COVID-19 pandemic, we may not be able to generate substantial revenue from TEGSEDI or WAYLIVRA sales.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If government or other third-party payers fail to provide adequate coverage and payment rates for our medicines, including SPINRAZA, TEGSEDI,
    WAYLIVRA, eplontersen and tofersen, and our medicines in development, our revenue will be limited.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In both domestic and foreign markets, sales of our current and future products will depend in part upon the availability of coverage and
    reimbursement from third-party payers. The majority of patients in the U.S. who would fit within our target patient populations for our medicines have their healthcare supported by a combination of Medicare coverage, other government health programs
    such as Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may depend upon clinical and economic standards that disfavor new medicines when more established or lower cost therapeutic alternatives are
    already available or subsequently become available. Assuming coverage is approved, the resulting reimbursement payment rates might not be enough to make our medicines affordable. Even if favorable coverage status and adequate reimbursement rates are
    attained, less favorable coverage policies and reimbursement rates may be implemented in the future. Accordingly, SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in development, will face competition from other therapies and
    medicines for limited financial resources. We or our partners may need to conduct post-marketing studies to demonstrate the cost-effectiveness of any future products to satisfy third-party payers. These studies might require us to commit a significant
    amount of management time and financial and other resources. Third-party payers may never consider our future products as cost-effective. Adequate third-party coverage and reimbursement might not be available to enable us to maintain price levels
    sufficient to realize an appropriate return on investment in product development.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly sophisticated methods of
    controlling healthcare costs. In addition, in the U.S., no uniform policy of coverage and reimbursement for medicines exists among third-party payers. Therefore, coverage and reimbursement for medicines can differ significantly from payer to payer. For
    example, the Affordable Care Act, or ACA, was passed in March 2010, and substantially changed the way healthcare is financed by both governmental and private insurers and continues to significantly impact the U.S. pharmaceutical industry. There have
    been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts to repeal or replace certain aspects of the ACA. It is unclear how future litigation and healthcare reform measures will impact the ACA and our business.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Further, we believe that future coverage, reimbursement and pricing will likely be subject to increased restrictions both in the U.S. and
    in international markets. In the U.S., recent health reform measures have resulted in reductions in Medicare and other healthcare funding, and there have been several recent U.S. Congressional inquiries, legislation and executive orders designed to,
    among other things, reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and foster scientific innovation to promote better health care and improved health. In addition, the IRA, among other things, allows HHS to
    negotiate the price of certain single-source drugs covered under Medicare and imposes rebates under Medicare Part B and Medicare Part D. In an effort to curb Medicare patients&#8217; out-of-pocket costs for prescription drugs, the Part D redesign legislation
    requires manufacturers to contribute to the catastrophic coverage phase for Part D drugs as discounts through a manufacturer discount program. Furthermore, any reduction in reimbursement from Medicare and other government programs may result in a
    similar reduction in payments from private payers. Our future product sales may be subject to additional discounts from list price in the form of rebates and discounts provided to 340B covered entities. Changes to the 340B program or to Medicare or
    Medicaid programs at the federal or state level, including outcomes of ongoing litigation in our industry, may impact our product prices and rebate liability. Further, the Biden administration released an executive order on October 14, 2022, directing
    HHS to submit a report on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries. It is unclear whether or how this executive order or similar
    policy initiatives will be implemented in the future.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and
    biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
    other countries and bulk purchasing. Third-party coverage and reimbursement for medicines may not be available or adequate in either the U.S. or international markets, which would negatively affect the potential commercial success of our products, our
    revenue and our profits.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to compete effectively, our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our
    medicines in development, will not generate significant revenues.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our competitors engage in drug discovery throughout the world, are numerous, and include, among others, major pharmaceutical companies and
    specialized biopharmaceutical firms. In addition, other companies are engaged in developing RNA-targeted technology. Our competitors may succeed in developing medicines that are:</div>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">priced lower than our medicines;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">reimbursed more favorably by government and other third-party payers than our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">safer than our medicines;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more effective than our medicines; or</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">more convenient to use than our medicines.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These competitive developments could make our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our
    medicines in development, obsolete or non-competitive.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certain of our partners are pursuing other technologies or developing other medicines either on their own or in collaboration with others,
    including our competitors, to treat some of the same diseases our own collaborative programs target. Competition may negatively impact a partner&#8217;s focus on and commitment to our medicines and, as a result, could delay or otherwise negatively affect the
    commercialization of our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our competitors have substantially greater financial, technical and human resources than we do. In addition, many of these
    competitors have significantly greater experience than we do in conducting preclinical testing and human clinical studies of new pharmaceutical products, in obtaining FDA and other regulatory authorizations of such products and in commercializing such
    products. Accordingly, our competitors may succeed in obtaining regulatory authorization for products earlier than we do or more successfully commercialize their products.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are several pharmaceutical and biotechnology companies engaged in the development or commercialization in certain geographic markets
    of products against targets that are also targets of products in our development pipeline. For example:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Onasemnogene abeparvovec and risdiplam compete with SPINRAZA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patisiran, tafamidis, tafamidis meglumine and vutrisiran compete with TEGSEDI and could compete with eplontersen;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Acoramidis could compete with TEGSEDI and </span>eplontersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">;</span></div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ARO-APOC3, lomitapide and pegozafermin could compete with WAYLIVRA and olezarsen;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lanadelumab-flyo, C1 esterase inhibitor, berotralstat, C1 esterase inhibitor subcutaneous, garadacimab, and NTLA-2002 could compete with donidalorsen;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olpasiran and SLN360 could compete with pelacarsen; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">NI-204 could compete with tofersen.</div>
        </td>

  </tr>


</table>
  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA injection for intrathecal use is an antisense medicine indicated for the treatment of SMA patients of all ages approved in over
    50 countries. Specifically, SPINRAZA faces competition from onasemnogene abeparvovec, a gene therapy product that was approved in the U.S. in May 2019 and in the EU in May 2020 for the treatment of SMA, as well as risdiplam, an oral product for the
    treatment of SMA that was approved in the U.S. in August 2020 and in the EU in March 2021. Biogen has disclosed that SPINRAZA revenue has decreased primarily due to a reduction in demand as a result of increased competition and that future sales of
    SPINRAZA may be adversely affected by competing products.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally, companies that are developing medicines that target the same patient populations as our medicines in development may compete
    with us to enroll participants in the clinical trials for such medicines, which could make it more difficult for us to complete enrollment for these clinical trials.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our medicines could be subject to regulatory limitations following approval.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Following approval of a medicine, we and our partners must comply with comprehensive government regulations regarding the manufacture,
    marketing and distribution of medicines. Promotional communications regarding prescription medicines must be consistent with the information in the product&#8217;s approved labeling. We or our partners may not obtain the labeling claims necessary or
    desirable to successfully commercialize our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in development.</div>

  <div><br />
  </div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45</div>

    </div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA and foreign regulatory bodies have the authority to impose significant restrictions on an approved medicine through the product
    label and on advertising, promotional and distribution activities. For example:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI&#8217;s label contains a boxed warning for thrombocytopenia and glomerulonephritis;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI requires periodic blood and urine monitoring; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in the U.S., TEGSEDI is available only through a REMS program.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prescription medicines may be promoted only for the approved indication(s) in accordance with the approved label. The FDA and other
    agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, when approved, the FDA or a foreign regulatory authority may condition approval on the performance of post-approval
    clinical studies or patient monitoring, which could be time consuming and expensive. For example, in connection with the conditional marketing approval for WAYLIVRA in the EU, we are required to conduct a post-authorization safety study to evaluate the
    safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. If the results of such post-marketing studies are not satisfactory, the FDA, EC or other foreign regulatory authorities may withdraw marketing authorization or may
    condition continued marketing on commitments from us or our partners that may be expensive and time consuming to fulfill.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 39.6pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or others identify side effects after any of our medicines are on the market, or if manufacturing problems occur subsequent to
    regulatory approval, or if we, our manufacturers or our partners fail to comply with regulatory requirements, we or our partners may, among other things, lose regulatory approval and be forced to withdraw products from the market, need to conduct
    additional clinical studies, incur restrictions on the marketing, distribution or manufacturing of the product, and/or change the labeling of our medicines.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with Biogen for the development and commercialization of SPINRAZA.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with Biogen to develop and commercialize SPINRAZA. We entered into this collaboration
    primarily to:</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fund our development activities for SPINRAZA;</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain regulatory approvals for SPINRAZA; and</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successfully commercialize SPINRAZA.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Biogen to obtain additional regulatory approvals for SPINRAZA, generate additional clinical data for SPINRAZA,
    manufacture, and continue to successfully commercialize SPINRAZA. In general, we cannot control the amount and timing of resources that Biogen devotes to our collaboration. If Biogen fails to further develop SPINRAZA, obtain additional regulatory
    approvals for SPINRAZA, manufacture or continue to successfully commercialize SPINRAZA, or if Biogen&#8217;s efforts in any of these respects are ineffective, revenues for SPINRAZA would be negatively affected.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our collaboration with Biogen may not continue for various reasons. Biogen can terminate our collaboration at any time. If
    Biogen stops developing or commercializing SPINRAZA, we would have to seek or spend additional funding, and SPINRAZA&#8217;s commercialization may be harmed or delayed.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on our collaboration with AstraZeneca for the joint development and commercialization of eplontersen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into a collaborative arrangement with AstraZeneca to develop and commercialize eplontersen. Under the terms of the
    collaboration agreement, we and AstraZeneca will co-develop and co-commercialize eplontersen in the U.S. and AstraZeneca will have the sole right to commercialize eplontersen in all other countries, except for certain Latin American countries. Prior to
    co-commercializing eplontersen in the U.S., we will need to negotiate a co-commercialization agreement with AstraZeneca to govern the parties&#8217; performance of co-commercialization, which agreement will include a commercial plan and budget. As a company
    we do not have experience with co-commercialization arrangements. We also do not have control over the amount and timing of resources that AstraZeneca devotes to our collaboration, particularly outside of the U.S. If the co-commercialization
    arrangement for eplontersen is not successful for any reason, eplontersen may not meet our commercial objectives and our revenues for eplontersen may be limited.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, a Joint Steering Committee, or JSC, having equal membership from us and AstraZeneca, and various subcommittees oversee and
    coordinate the development, manufacturing, commercialization and other exploitation activities for eplontersen in the U.S. by mutual agreement. If any subcommittee cannot reach unanimous agreement on any matter within its respective scope of authority,
    such matter may be referred to the JSC for resolution. If the JSC cannot come to a mutual agreement on any particular matter, this could delay our ability to develop or commercialize eplontersen.</div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we are not successful in expanding our manufacturing capabilities or cannot manufacture our medicines or contract with a third party to
    manufacture our medicines at costs that allow us to charge competitive prices to buyers, we cannot market our products profitably.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To successfully commercialize any of our medicines, we need to optimize and manage large-scale commercial manufacturing capabilities
    either on a standalone basis or through a third-party manufacturer. As our drug development and commercial pipeline increases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. To that end, we have begun
    work on a new manufacturing facility in Oceanside, California that will expand our manufacturing infrastructure. We will incur substantial expenditures to build our new manufacturing facility and, following its completion, will likely need to hire and
    train additional staff to operate the facility. If we are not successful in executing this expansion, it could limit our ability to meet our manufacturing requirements and commercial objectives in the future.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, we have limited experience manufacturing pharmaceutical products of the chemical class represented by our medicines, called
    oligonucleotides, on a commercial scale for the systemic administration of a medicine. There are a small number of suppliers for certain capital equipment and raw materials that we use to manufacture our medicines, and some of these suppliers will need
    to increase their scale of production to meet our projected needs for commercial manufacturing. Further, we must continue to improve our manufacturing processes to allow us to reduce our drug costs. We or our partners may not be able to manufacture our
    medicines at a cost or in quantities necessary to make commercially successful products.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturers, including us, must adhere to the FDA&#8217;s cGMP regulations and similar regulations in foreign countries, which the applicable
    regulatory authorities enforce through facilities inspection programs. We, our partners and our contract manufacturers may not comply or maintain compliance with cGMP, or similar foreign regulations. Non-compliance could significantly delay or prevent
    receipt of marketing authorizations for our medicines, including authorizations for SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in development, or could result in enforcement action after authorization that might limit the
    commercial success of our medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, and our medicines in development.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We rely on third-party manufacturers to supply the drug substance and drug product for TEGSEDI and drug product for WAYLIVRA. Any delays
    or disruption to our own or third-party commercial manufacturing capabilities, including any interruption to our supply chain as a result of the COVID-19 pandemic or the ongoing war between Russia and Ukraine, could limit the commercial success of our
    medicines.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are relying on third parties to market, sell and distribute TEGSEDI and WAYLIVRA.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have entered into agreements with third parties to commercialize TEGSEDI and WAYLIVRA as follows:</div>

  <div><br />
  </div>

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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we entered into a distribution agreement with Sobi to commercialize TEGSEDI in the U.S. and Canada;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a distribution agreement with Sobi to commercialize TEGSEDI and WAYLIVRA in Europe; and</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In August 2018, we granted PTC the exclusive right to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</div>
        </td>

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  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are relying on Sobi and PTC to effectively market, sell and distribute TEGSEDI and WAYLIVRA and have less control over sales efforts
    and may receive less revenue than if we commercialized TEGSEDI or WAYLIVRA by ourselves. If Sobi or PTC does not successfully commercialize TEGSEDI or WAYLIVRA, including as a result of delays or disruption caused by the COVID-19 pandemic, we may
    receive limited revenue for TEGSEDI or WAYLIVRA in the U.S., Canada, Europe, Latin America or certain Caribbean countries, which could adversely affect our business, prospects, financial condition and results of operations.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Related to the Development and Regulatory Approval of our Medicines</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we or our partners fail to obtain regulatory approval for our medicines and additional approvals for SPINRAZA, TEGSEDI and WAYLIVRA, we
    or our partners cannot sell them in the applicable markets.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot guarantee that any of our medicines will be considered safe and effective or will be approved for commercialization. In
    addition, it is possible that SPINRAZA, TEGSEDI and WAYLIVRA may not be approved in additional markets or for additional indications. We and our partners must conduct time-consuming, extensive and costly clinical studies to demonstrate the safety and
    efficacy of each of our medicines before they can be approved or receive additional approvals for sale. We and our partners must conduct these studies in compliance with FDA regulations and with comparable regulations in other countries.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partners may not obtain necessary regulatory approvals on a timely basis, if at all, for our medicines. It is possible that
    regulatory agencies will not approve our medicines for marketing or SPINRAZA, TEGSEDI or WAYLIVRA in additional markets or for additional indications. If the FDA or another regulatory agency believes that we or our partners have not sufficiently
    demonstrated the safety or efficacy of any of our medicines, including SPINRAZA, TEGSEDI and WAYLIVRA, or our medicines in development, the agency will not approve the specific medicine or will require additional studies, which could be time consuming
    and expensive and delay or harm commercialization of the medicine. For example, in August 2018 we received a complete response letter from the FDA regarding the new drug application for WAYLIVRA in which the FDA determined that the safety concerns
    identified with WAYLIVRA in our clinical development program outweighed the expected benefits of triglyceride lowering in patients with FCS. We also received a Non-W from Health Canada for WAYLIVRA in November 2018.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The FDA or other comparable foreign regulatory authorities can delay, limit or deny approval of a medicine for many reasons, including:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the design or implementation of our clinical studies;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate to the satisfaction of the FDA or other regulatory authorities that a medicine is safe and effective for any indication;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may not accept clinical data from studies conducted at clinical facilities that have deficient clinical practices or that are in countries where the
            standard of care is potentially different from the U.S.;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may be unable to demonstrate that our medicine&#8217;s clinical and other benefits outweigh its safety risks to support approval;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may disagree with the interpretation of data from preclinical or clinical studies;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">such authorities may find deficiencies in the manufacturing processes or facilities of third-party manufacturers who manufacture clinical and commercial supplies for our
            medicines, or may delay the inspection of such facilities due to restrictions related to the COVID-19 pandemic; and</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the approval policies or regulations of such authorities or their prior guidance to us or our partners during clinical development may significantly change in a manner
            rendering our clinical data insufficient for approval.</div>
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</table>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Failure to receive marketing authorization for our medicines, or failure to receive additional marketing authorizations for SPINRAZA,
    TEGSEDI or WAYLIVRA, or delays in these authorizations, could prevent or delay commercial introduction of the medicine, and, as a result, could negatively impact our ability to generate revenue from product sales.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the results of clinical testing indicate that any of our medicines are not suitable for commercial use, we may need to abandon one or
    more of our drug development programs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery and drug development have inherent risks and the historical failure rate for drugs is high. Antisense medicines are a
    relatively new approach to therapeutics. If we cannot demonstrate that our medicines are safe and effective for human use in the intended indication(s), we may need to abandon one or more of our drug development programs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even if our medicines are successful in preclinical and human clinical studies, the medicines may not be successful in late-stage clinical
    studies.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Successful results in preclinical or initial human clinical
      studies, including the Phase 2 results for some of our medicines in development, may not predict the results of subsequent clinical studies. If any of our medicines in Phase 3 clinical studies, including the studies of donidalorsen, </span>eplontersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, ION363, olezarsen, pelacarsen and tofersen, do not show sufficient efficacy in patients with the targeted indication, or if such studies are discontinued for any other reason,
      it could negatively impact our development and commercialization goals for these medicines and our stock price could decline.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the past, we have invested in clinical studies of
      medicines that have not met the primary clinical endpoints in their Phase 3 studies or have been discontinued for other reasons. For example, in October 2021, Biogen reported that tofersen did not meet the primary clinical endpoint in the Phase 3
      VALOR study; however, trends favoring tofersen were seen across multiple secondary and exploratory measures of disease activity and clinical function. In addition, in March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study
      of tominersen in patients with manifest Huntington&#8217;s disease based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded Independent Data Monitoring Committee. Similar results could occur in clinical studies
      for our other medicines, including the studies of donidalorsen, </span>eplontersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, ION363, olezarsen, pelacarsen and tofersen.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">There are a number of factors that could cause a clinical study to fail or be delayed, including:</div>

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    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the clinical study may produce negative or inconclusive results;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">regulators may require that we hold, suspend or terminate clinical research for noncompliance with regulatory requirements;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we, our partners, the FDA or foreign regulatory authorities could suspend or terminate a clinical study due to adverse side effects of a medicine on subjects or lack of
            efficacy in the trial;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners may decide, or regulators may require us, to conduct additional preclinical testing or clinical studies;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">enrollment in our clinical studies may be slower than we anticipate;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">we or our partners, including our independent clinical investigators, contract research organizations and other third-party service providers on which we rely, may not
            identify, recruit and train suitable clinical investigators at a sufficient number of study sites or timely enroll a sufficient number of study subjects in the clinical study;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the institutional review board for a prospective site might withhold or delay its approval for the study;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">people who enroll in the clinical study may later drop out due to adverse events, a perception they are not benefiting from participating in the study, fatigue with the
            clinical study process or personal issues;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">a clinical study site may deviate from the protocol for the study;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the cost of our clinical studies may be greater than we anticipate;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our partners may decide not to exercise any existing options to license and conduct additional clinical studies for our medicines; and</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the supply or quality of our medicines or other materials necessary to conduct our clinical studies may be insufficient, inadequate or delayed.</div>
        </td>

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  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The COVID-19 pandemic could make some of these factors more likely to occur.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, our current medicines, including SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen are chemically similar to each other.
    As a result, a safety observation we encounter with one of our medicines could have, or be perceived by a regulatory authority to have, an impact on a different medicine we are developing. This could cause the FDA or other regulators to ask questions
    or take actions that could harm or delay our ability to develop and commercialize our medicines or increase our costs. For example, the FDA or other regulatory agencies could request, among other things, additional information or commitments before we
    can start or continue a clinical study, protocol amendments, increased safety monitoring, additional product labeling information, and post-approval commitments. This happened in connection with the conditional marketing approval for WAYLIVRA in the
    EU, as the EC is requiring us to conduct a post-authorization safety study to evaluate the safety of WAYLIVRA on thrombocytopenia and bleeding in FCS patients taking WAYLIVRA. We have ongoing post-marketing studies for WAYLIVRA and TEGSEDI and an EAP
    for WAYLIVRA. Adverse events or results from these studies or the EAPs could negatively impact our pending or future marketing approval applications for WAYLIVRA and TEGSEDI in patients with FCS or ATTRv-PN, respectively, or the commercial opportunity
    for WAYLIVRA or TEGSEDI.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any failure or delay in our clinical studies, including the studies of donidalorsen, eplontersen, ION363, olezarsen, pelacarsen and
    tofersen, could reduce the commercial potential or viability of our medicines.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We depend on third parties to conduct clinical studies for our medicines and any failure of those parties to fulfill their obligations
    could adversely affect our development and commercialization plans.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depend on independent clinical investigators, contract research organizations and other third-party service providers to conduct our
    clinical studies for our medicines and expect to continue to do so in the future. For example, we use clinical research organizations, such as Icon Clinical Research Limited, Medpace, Inc., Parexel International Corporation, Syneos Health, Inc. and
    Thermo Fisher Scientific Inc. for the clinical studies for our medicines, including donidalorsen, eplontersen, ION363, olezarsen, pelacarsen and tofersen. We rely heavily on these parties for successful execution of our clinical studies, but do not
    control many aspects of their activities. For example, the investigators are not our employees, but we are responsible for ensuring that such investigators conduct each of our clinical studies in accordance with the general investigational plan and
    approved protocols for the study. Third parties may not complete activities on schedule or may not conduct our clinical studies in accordance with regulatory requirements or our stated protocols. For example, some of our key vendors are experiencing
    labor shortages, which could impact their ability to perform services for us for certain of our clinical trials. The failure of these third parties to carry out their obligations, including as a result of delays or disruptions caused by the COVID-19
    pandemic, or a termination of our relationship with such third parties, could delay or prevent the development, marketing authorization and commercialization of our medicines or additional marketing authorizations for TEGSEDI and WAYLIVRA.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, while we do not have any clinical trial sites in Ukraine, we do have a limited number of clinical trial sites in Russia and
    surrounding countries that may be impacted by the ongoing war between Russia and Ukraine and could result in difficulties enrolling or completing our clinical trials in such areas on schedule. Furthermore, the U.S. and its European allies have imposed
    significant sanctions against Russia, including regional embargoes, full blocking sanctions, and other restrictions targeting major Russian financial institutions. The U.S. government has also indicated it will consider imposing additional sanctions
    and other similar measures in the future. Our ability to conduct clinical trials in Russia may become restricted under applicable sanctions laws, which would require us to identify alternative trial sites, and could increase our costs and delay the
    clinical development of certain of our medicines.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Since corporate partnering is a significant part of our strategy to fund the advancement and commercialization of our development
    programs, if any of our collaborative partners fail to fund our collaborative programs, or if we cannot obtain additional partners, we may have to delay or stop progress on our drug development programs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To date, corporate partnering has played a significant role in our strategy to fund our development programs and to add key development
    resources. We plan to continue to rely on additional collaborative arrangements to develop and commercialize some of our unpartnered medicines. However, we may not be able to negotiate favorable collaborative arrangements for these drug programs. If we
    cannot continue to secure additional collaborative partners, our revenues could decrease and the development of our medicines could suffer.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our corporate partners are developing and funding many of the medicines in our development pipeline. For example, we are relying on:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">AstraZeneca for the joint development and funding of eplontersen;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Novartis for development and funding of pelacarsen;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen for development and funding of tofersen;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Biogen for additional studies of SPINRAZA; and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">GSK for development and funding of bepirovirsen.</div>
        </td>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If any of these pharmaceutical companies stops developing and funding these medicines, our business could suffer and we may not have, or
    be willing to dedicate, the resources available to develop these medicines on our own. Our collaborators can terminate their relationships with us under certain circumstances, many of which are outside of our control. For example, in 2022, Pfizer and
    Bayer decided to discontinue the clinical development programs for vupanorsen and fesomersen, respectively.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Even with funding from corporate partners, if our partners do not effectively perform their obligations under our agreements with them, it
    would delay or stop the progress of our drug development and commercial programs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to receiving funding, we enter into collaborative arrangements with third parties to:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">conduct clinical studies;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">seek and obtain marketing authorizations; and</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">manufacture and commercialize our medicines.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Once we have secured a collaborative arrangement to further develop and commercialize one of our drug development programs, such as our
    collaborations with AstraZeneca, Biogen, GSK, Novartis, and Roche, these collaborations may not continue or result in commercialized medicines, or may not progress as quickly as we anticipated.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For example, a collaborator such as AstraZeneca, Biogen, GSK, Novartis, or Roche, could determine that it is in its financial interest to:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue alternative technologies or develop alternative products that may be competitive with the medicine that is part of the collaboration with us;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">pursue higher-priority programs or change the focus of its own development programs; or</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">choose to devote fewer resources to our medicines than it does to its own medicines.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If any of these occur, it could affect our partner&#8217;s
      commitment to the collaboration with us and could delay or otherwise negatively affect the commercialization of our medicines, including SPINRAZA, eplontersen, pelacarsen and </span>tofersen<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be able to benefit from orphan drug designation for our medicines.</div>

  <div style="text-align: justify; text-indent: 40.8pt; margin-top: 12pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the U.S., under the Orphan Drug Act, the FDA may designate a medicine as an orphan drug if it is intended to treat
    a rare disease or condition affecting fewer than 200,000 individuals in the U.S. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process, but it can provide financial incentives,
    such as tax advantages and user-fee waivers, as well as longer regulatory exclusivity periods. The FDA has granted orphan drug designation to eplontersen for the treatment of patients with transthyretin-mediated amyloidosis and to ION582 for the
    treatment of patients with Angelman syndrome. The FDA and EMA have granted orphan drug designation to TEGSEDI for the treatment of patients with ATTRv-PN, to WAYLIVRA for the treatment of patients with FCS, and to tominersen for the treatment of
    patients with HD. In addition, the EMA has granted orphan drug designation to WAYLIVRA for the treatment of patients with FPL. Even if approval is obtained on a medicine that has been designated as an orphan drug, we may lose orphan drug exclusivity if
    the FDA or EMA determines that the request for designation was materially defective or if we cannot assure sufficient quantity of the applicable medicine to meet the needs of patients with the rare disease or condition, or if a competitor is able to
    gain approval for the same medicine in a safer or more effective form or that makes a major contribution to patient care. If we lose orphan drug exclusivity on any of our medicines, we may face increased competition and lose market share for such
    medicine.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Risks Associated with our Businesses as a Whole</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our financial condition</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we fail to obtain timely funding, we may need to curtail or abandon some of our programs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Many of our medicines are undergoing clinical studies or are in the early stages of research and development. Most of our programs will
    require significant additional research, development, manufacturing, preclinical and clinical testing, marketing authorizations, preclinical activities and commitment of significant additional resources prior to their successful commercialization. In
    addition, as we commercialize more medicines on our own, we will need to invest significant financial resources to continue developing the infrastructure required to successfully commercialize our medicines, including the build-out of a new
    manufacturing facility. All of these activities will require significant cash. As of December 31, 2022, we had cash, cash equivalents and
    short-term investments equal to $2.0 billion. If we or our partners do not meet our goals to successfully commercialize our medicines,
    including SPINRAZA, TEGSEDI and WAYLIVRA, or to license certain medicines and proprietary technologies, we will need additional funding in the future. Our future capital requirements will depend on many factors such as:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">successful commercialization of SPINRAZA, TEGSEDI and WAYLIVRA;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the profile and launch timing of our medicines, including donidalorsen, eplontersen, ION363, olezarsen, pelacarsen and tofersen;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in existing collaborative relationships and our ability to establish and maintain additional collaborative arrangements;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">continued scientific progress in our research, drug discovery and development programs;</div>
        </td>

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</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the size of our programs and progress with preclinical and clinical studies;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">the time and costs involved in obtaining marketing authorizations;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">competing technological and market developments, including the introduction by others of new therapies that address our markets; and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">our manufacturing requirements and capacity to fulfill such requirements.</div>
        </td>

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</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we need additional funds, we may need to raise them through public or private financing. Additional financing may not be available on
    acceptable terms or at all. If we raise additional funds by issuing equity securities, the shares of existing stockholders will be diluted and the price, as well as the price of our other securities, may decline. If adequate funds are not available or
    not available on acceptable terms, we may have to cut back on one or more of our research, drug discovery or development programs. Alternatively, we may obtain funds through arrangements with collaborative partners or others, which could require us to
    give up rights to certain of our technologies or medicines.</div>

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  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We have incurred losses, and our business will suffer if we fail to consistently achieve profitability in the future.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because drug discovery and development require substantial lead-time and money prior to commercialization, our expenses have generally
    exceeded our revenue since we were founded in January 1989. As of December 31, 2022, we had an accumulated deficit of approximately $1.4 billion and stockholders&#8217; equity of approximately $0.6
    billion. Most of our historical losses resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations. Most of our income has historically come
    from collaborative arrangements, including commercial revenue from royalties and R&amp;D revenue, with additional income from research grants and the sale or licensing of our patents, as well as interest income. We will now and continuing into the
    foreseeable future need to invest significant financial resources to develop capabilities to commercialize medicines on our own and expect that our income in the future will be driven primarily by commercial sales. If we do not earn substantial revenue
    from commercial sales, we may incur additional operating losses in the future, which could restrict our ability to successfully develop additional medicines or sustain future profitability.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We may not be entitled to obtain additional milestone payments under our royalty monetization agreement with Royalty Pharma.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a Royalty Purchase Agreement with Royalty Pharma Investments. In addition to the $500 million we received
    at closing, this agreement makes available to us up to an additional $625 million in milestone payments. However, these additional milestone payments are subject to satisfaction of certain conditions related to the regulatory approval or commercial
    sales of pelacarsen, in certain cases by specific deadlines. Should we not satisfy such conditions by the applicable deadlines, or if we fail to meet our obligations or default under this agreement, the actual amount of additional payments to us could
    be substantially less than the maximum amounts available thereunder.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our intellectual property</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we cannot protect our patent rights or our other proprietary rights, others may compete more effectively against us.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our success depends to a significant degree upon whether we can continue to develop, secure and maintain intellectual property rights to
    proprietary products and services. However, we may not receive issued patents on any of our pending patent applications in the U.S. or in other countries and we may not be able to obtain, maintain or enforce our patents and other intellectual property
    rights, any of which could impact our ability to compete effectively. In addition, the scope of any of our issued patents may not be sufficiently broad to provide us with a competitive advantage. Furthermore, other parties may successfully challenge,
    invalidate or circumvent our issued patents or patents licensed to us so that our patent rights do not create an effective competitive barrier or revenue source.</div>

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  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We cannot be certain that the U.S. Patent and Trademark Office, or U.S. PTO, and courts in the U.S. or the patent offices and courts in
    foreign countries will consider the claims in our patents and applications covering SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, or any of our medicines in development as patentable. Method-of-use patents protect the use of a product for the
    specified method. This type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively
    promote their product for our targeted indications, physicians may prescribe these products off-label. Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such
    infringement is difficult to prevent, even through legal action.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we or any licensor partner loses or cannot obtain patent protection for SPINRAZA, TEGSEDI, WAYLIVRA, eplontersen and tofersen, or any
    of our medicines in development, it could have a material adverse impact on our business.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intellectual property litigation could be expensive and prevent us from pursuing our programs.</div>

  <div><br />
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we have to defend our intellectual property rights. If we are involved in an intellectual property dispute, we may need
    to litigate to defend our rights or assert them against others. Disputes can involve arbitration, litigation or proceedings declared by the U.S. PTO or the International Trade Commission or foreign patent authorities. Even if resolved in our favor,
    litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public
    announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If a third party claims that our medicines or technology infringe its patents or other intellectual property rights, we may have to
    discontinue an important product or product line, alter our products and processes, pay license fees or cease certain activities. We may not be able to obtain a license to needed intellectual property on favorable terms, if at all. There are many
    patents issued or applied for in the biotechnology industry, and we may not be aware of patents or patent applications held by others that relate to our business. This is especially true since patent applications in the U.S. are filed confidentially
    for the first 18 months. Moreover, the validity and breadth of biotechnology patents involve complex legal and factual questions for which important legal issues remain.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to product liability</div>

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  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are exposed to potential product liability claims, and insurance against these claims may not be available to us at a reasonable rate
    in the future or at all.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business exposes us to potential product liability risks that are inherent in the testing, manufacturing, marketing and sale of
    therapeutic products, including potential product liability claims related to SPINRAZA, TEGSEDI and WAYLIVRA, and our medicines in development. We have clinical study insurance coverage and commercial product liability insurance coverage. However, this
    insurance coverage may not be adequate to cover claims against us, or be available to us at an acceptable cost, if at all. Regardless of their merit or eventual outcome, product liability claims may result in decreased demand for our medicines, injury
    to our reputation, withdrawal of clinical study volunteers and loss of revenues. Thus, whether or not we are insured, a product liability claim or product recall may result in losses that could be material.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our personnel</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">The loss of key personnel, or the inability to attract and retain highly skilled personnel, could make it more difficult to run our
    business and reduce our likelihood of success.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are dependent on the principal members of our management
      and scientific staff, and as we move towards commercializing medicines on our own, we will become increasingly dependent on the principal members of our commercial team. We do not have employment agreements with any of our employees that would
      prevent them from leaving us. The loss of our management, key scientific or commercial employees might slow the achievement of important research and development or commercial goals. It is also critical to our success that we recruit and retain
      qualified scientific personnel to perform research and development work. We may not be able to attract and retain skilled and experienced scientific personnel on acceptable terms because of intense competition for experienced scientists among many
      pharmaceutical and health care companies, universities and non-profit research institutions. In addition, failure to succeed in clinical studies may make it more challenging to recruit and retain qualified scientific personnel</span>.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to the COVID-19 pandemic and other events</div>

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  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business may be adversely affected by pandemics, climate change, extreme weather events, earthquakes, war, civil or political unrest,
    terrorism or other catastrophic events.</div>

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  <div style="text-align: justify; text-indent: 40.5pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our business could be adversely affected by health
      epidemics in regions where we or our partners are commercializing our medicines, have concentrations of clinical trial sites or other business operations, and could cause disruption in the operations of third-party manufacturers and contract research
      organizations upon whom we rely. For example, some physician and hospital policies that were put in place as a result of the COVID-19 pandemic restricted in-person access by third parties, which in some cases impacted our commercialization efforts
      for TEGSEDI and WAYLIVRA. In addition, in December 2021, Novartis announced that enrollment for the Phase 3 HORIZON study had been delayed due to the COVID-19 pandemic.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The COVID-19 pandemic continues to evolve, and while we believe we have not experienced material adverse effects to our business as a result of the COVID-19 pandemic, the ultimate impact of the COVID-19 pandemic or a similar health epidemic
      is highly uncertain.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In recent years, extreme weather events and changing weather patterns have become more common. As a result, we are potentially exposed to
    varying natural disaster or extreme weather risks such as hurricanes, tornadoes, fires, droughts, floods, or other events that may result from the impact of climate change on the environment. The potential impacts of climate change may also include
    increased operating costs associated with additional regulatory requirements and investments in reducing energy, water use and greenhouse gas emissions. In addition, we currently manufacture most of our research and clinical supplies in a manufacturing
    facility located in Carlsbad, California and will move such manufacturing to our new facility in Oceanside, California once it is built. We manufacture the finished drug product for TEGSEDI and WAYLIVRA at third-party contract manufacturers. Biogen
    manufactures the finished drug product for SPINRAZA. The facilities and the equipment we, our partners and our contract manufacturers use to research, develop and manufacture our medicines would be costly to replace and could require substantial lead
    time to repair or replace. Our facilities or those of our partners or contract manufacturers may be harmed by natural disasters or other events outside our control, such as earthquakes, war, civil or political unrest, deliberate acts of sabotage,
    terrorism or industrial accidents such as fire and explosion, whether due to human or equipment error, and if such facilities are affected by a disaster or other event, our development and commercialization efforts would be delayed. Although we possess
    property damage and business interruption insurance coverage, this insurance may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all. In addition, our development and
    commercialization activities could be harmed or delayed by a shutdown of the U.S. government, including the FDA.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to cybersecurity</div>

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  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We are dependent on information technology systems, infrastructure and data, which exposes us to data security risks.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are dependent upon our own and third-party information technology systems, infrastructure and data, including mobile technologies, to
    operate our business. The multitude and complexity of our computer systems may make them vulnerable to service interruption or destruction, disruption of data integrity, malicious intrusion, or random attacks. Likewise, data privacy or security
    incidents or breaches by employees or others may pose a risk that sensitive data, including our intellectual property, trade secrets or personal information of our employees, patients, customers or other business partners may be exposed to unauthorized
    persons or to the public. Cyber-attacks are increasing in their frequency, sophistication and intensity, with third-party phishing and social engineering attacks in particular increasing during the COVID-19 pandemic. In addition, the number and
    frequency of cybersecurity events globally may be heightened during times of geopolitical tension or instability between countries, including, for example, the ongoing war between Russia and Ukraine, as a result of which several companies (not
    including us) have reported recent cybersecurity events.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cyber-attacks could include the deployment of harmful malware, denial-of-service, social engineering and other means to affect service
    reliability and threaten data confidentiality, integrity and availability. Our business partners face similar risks and any security breach of their systems could adversely affect our security posture. A security breach or privacy violation that leads
    to disclosure or modification of or prevents access to patient information, including personally identifiable information or protected health information, could harm our reputation, compel us to comply with federal and state breach notification laws
    and foreign law equivalents, subject us to financial penalties and mandatory and costly corrective action, require us to verify the correctness of database contents and otherwise subject us to litigation or other liability under laws and regulations
    that protect personal data, any of which could disrupt our business and result in increased costs or loss of revenue. Moreover, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches, which
    could lead to the loss of confidential information, trade secrets or other intellectual property. While we have invested, and continue to invest, in the protection of our data and information technology infrastructure, our efforts may not prevent
    service interruptions or identify breaches in our systems that could adversely affect our business and operations and result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm to us.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to our securities and the global credit markets</div>

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  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If we do not progress in our programs as anticipated, the price of our securities could decrease.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For planning purposes, we estimate and may disclose the timing of a variety of clinical, regulatory and other milestones, such as when we
    anticipate a certain medicine will enter clinical trials, when we anticipate completing a clinical study, or when we anticipate filing an application for, or obtaining, marketing authorization, or when we or our partners plan to commercially launch a
    medicine. We base our estimates on present facts and a variety of assumptions, many of which are outside of our control, including the impacts of the COVID-19 pandemic. If we do not achieve milestones in accordance with our or our investors&#8217; or
    securities analysts&#8217; expectations, including milestones related to SPINRAZA, TEGSEDI, WAYLIVRA, donidalorsen, eplontersen, ION363, olezarsen, pelacarsen and tofersen, the price of our securities could decrease.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">If the price of our securities continues to be highly volatile, this could make it harder to liquidate your investment and could increase
    your risk of suffering a loss.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The market price of our common stock, like that of the securities of many other biopharmaceutical companies, has been and is likely to
    continue to be highly volatile. These fluctuations in our common stock price may significantly affect the trading price of our securities. During the 12 months preceding December 31, 2022, the market price of our common stock ranged from $48.82 to $28.25 per share. Many factors can affect the market price of our securities, including, for example, fluctuations in our operating results, announcements
    of collaborations, clinical study results, technological innovations or new products being developed by us or our competitors, the commercial success of our approved medicines, governmental regulation, marketing authorizations, changes in payers&#8217;
    reimbursement policies, developments in patent or other proprietary rights and public concern regarding the safety of our medicines.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Broad market factors may materially harm the market price of our common stock irrespective of our operating performance. For example, the
    COVID-19 pandemic caused a significant disruption of global financial markets and resulted in increased volatility in the trading price of our common stock. The global credit and financial markets may also be adversely affected by the ongoing war
    between Russia and Ukraine and measures taken in response thereto. In addition, industry factors may materially harm the market price of our common stock. Nasdaq, and the market for biotechnology companies in particular, have historically experienced
    extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of the particular companies affected. The trading prices and valuations of these stocks, and of ours, may not be predictable. A loss
    of investor confidence in the market for biotechnology or pharmaceutical stocks or the stocks of other companies that investors perceive to be similar to us, the opportunities in the biotechnology and pharmaceutical market or the stock market in
    general, could depress our stock price regardless of our business, prospects, financial conditions or results of operations.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Provisions in our certificate of incorporation, convertible notes documents, call spread hedge transaction documents and Delaware law may
    prevent stockholders from receiving a premium for their shares.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation provides for classified terms for the members of our board of directors. Our certificate also includes a
    provision that requires at least 66 2/3 percent of our voting stockholders to approve a merger or certain other business transactions with, or proposed by, any holder of 15 percent or more of our voting stock, except in cases where certain directors
    approve the transaction or certain minimum price criteria and other procedural requirements are met.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our certificate of incorporation also requires that any action required or permitted to be taken by our stockholders must be taken at a
    duly called annual or special meeting of stockholders and may not be taken by written consent. In addition, only our board of directors, chairman of the board or chief executive officer can call special meetings of our stockholders. We have in the
    past, and may in the future, implement a stockholders&#8217; rights plan, also called a poison pill, which could make it uneconomical for a third party to acquire our company on a hostile basis. In addition, our board of directors has the authority to fix
    the rights and preferences of, and issue shares of preferred stock, which may have the effect of delaying or preventing a change in control of our company without action by our stockholders.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The provisions of our convertible senior notes could make it more difficult or more expensive for a third party to acquire us. Upon the
    occurrence of certain transactions constituting a fundamental change, holders of the notes will have the right, at their option, to require us to repurchase all of their notes or a portion of their notes, which may discourage certain types of
    transactions in which our stockholders might otherwise receive a premium for their shares over the then-current market prices.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2021, we completed a $632.5 million offering of 0%
      Notes and used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million of our 1% Notes for $257.0 million. In December 2019, we entered into privately negotiated exchange and/or subscription agreements with
      certain new investors and certain holders of our existing 1% Notes to exchange $375.6 million of our 1% Notes for $439.3 million of our 0.125% Notes, and to issue $109.5 million of our 0.125% Notes. Additionally, in connection with the pricing of our
      0% Notes and 0.125% Notes, we entered into call spread transactions in which we purchased note hedges and sold warrants. Terminating or unwinding the call spread transactions could require us to make substantial payments to the counterparties under
      those agreements or may increase our stock price. The costs or any increase in stock price that may arise from terminating or unwinding such agreements could make an acquisition of our company significantly more expensive to the purchaser.</span></div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These provisions, as well as Delaware law, including Section 203 of the Delaware General Corporation Law, and other of our agreements, may
    discourage certain types of transactions in which our stockholders might otherwise receive a premium for their shares over then-current market prices, and may limit the ability of our stockholders to approve transactions that they think may be in their
    best interests.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Future sales of our common stock in the public market could adversely affect the trading price of our securities.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Future sales of substantial amounts of our common stock in the public market, or the perception that such sales could occur, could
    adversely affect trading prices of our securities. For example, we may issue approximately 17.5 million shares of our common stock upon conversion of our 0% Notes and 0.125% Notes, up to 10.9 million shares in connection with the warrant transactions
    we entered into in connection with the issuance of our 0% Notes, and up to 6.6 million shares in connection with the warrant transactions we entered into in connection with the issuance of our 0.125% Notes, in each case subject to customary
    anti-dilution adjustments. The addition of any of these shares into the public market may have an adverse effect on the price of our securities.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, pursuant to the call spread transactions we entered into in connection with the pricing of our 0% Notes and 0.125% Notes, the
    counterparties are likely to modify their hedge positions from time to time at or prior to the conversion or maturity of the notes by purchasing and selling shares of our common stock, other of our securities, or other instruments, including
    over-the-counter derivative instruments, that they may wish to use in connection with such hedging, which may have a negative effect on the conversion value of those notes and an adverse impact on the trading price of our common stock. The call spread
    transactions are expected generally to reduce potential dilution to holders of our common stock upon any conversion of our 0% Notes or 0.125% Notes or offset any cash payments we are required to make in excess of the principal amount of the converted
    0% Notes or 0.125% Notes, as the case may be. However, the warrant transactions could separately have a dilutive effect to the extent that the market value per share of our common stock exceeds the applicable strike price of the warrants.</div>

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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Negative conditions in the global credit markets and financial services and other industries may adversely affect our business.</div>

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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The global credit markets, the financial services industry, the U.S. capital markets, and the U.S. economy as a whole have recently
    experienced substantial turmoil and uncertainty characterized by unprecedented intervention by the U.S. federal government in response to the COVID-19 pandemic. While the potential economic impact brought by, and the duration of, the COVID-19 pandemic
    may be difficult to assess or predict, it could result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity. In addition, a recession or market
    correction resulting from the spread of COVID-19 could materially affect our business and has and could continue to affect the value of our securities. In addition, the global credit and financial markets may be adversely affected by the ongoing war
    between Russia and Ukraine and measures taken in response thereto. In the past, the failure, bankruptcy, or sale of various financial and other institutions created similar turmoil and uncertainty in such markets and industries. It is possible that a
    similar crisis in the global credit markets, the U.S. capital markets, the financial services industry or the U.S. economy may adversely affect our business, vendors and prospects, as well as our liquidity and financial condition. Additionally, our
    insurance carriers and insurance policies covering all aspects of our business may become financially unstable or may not be sufficient to cover any or all of our losses and may not continue to be available to us on acceptable terms, or at all. In
    addition, due to the rapidly rising inflation rate, we may experience significantly increased costs of goods and services for our business.</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A variety of risks associated with operating our business and marketing our medicines internationally could adversely affect our business. In
    addition to our U.S. operations, we are commercializing TEGSEDI in the EU, Canada, Latin America and certain Caribbean countries, and WAYLIVRA in the EU, Latin America and certain Caribbean countries. We face risks associated with our international
    operations, including possible unfavorable regulatory, pricing and reimbursement, political, tax and labor conditions, which could harm our business. Because we have international operations, we are subject to numerous risks associated with
    international business activities, including:</div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with differing or unexpected regulatory requirements for our medicines and foreign employees;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">complexities associated with managing multiple payer reimbursement regimes, government payers or patient self-pay systems;</div>
        </td>

  </tr>


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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">difficulties in staffing and managing foreign operations;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">in certain circumstances, increased dependence on the commercialization efforts and regulatory compliance of third-party distributors or strategic partners;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">foreign government taxes, regulations and permit requirements;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">U.S. and foreign government tariffs, trade restrictions, price and exchange controls and other regulatory requirements;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">anti-corruption laws, including the Foreign Corrupt Practices Act, or the FCPA, and its equivalent in foreign jurisdictions;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">economic weakness, including inflation, natural disasters, war, events of terrorism, political instability or public health issues or pandemics, such as the COVID-19
            pandemic, in particular foreign countries or globally;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenue, and other obligations related to doing business in
            another country;</div>
        </td>

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  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">compliance with tax, employment, privacy, immigration and labor laws, regulations and restrictions for employees living or traveling abroad;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">workforce uncertainty in countries where labor unrest is more common than in the U.S.; and</div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">changes in diplomatic and trade relationships.</div>
        </td>

  </tr>


</table>
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  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our business activities outside of the U.S. are subject to the FCPA and similar anti-bribery or anti-corruption laws, regulations or rules
    of other countries in which we operate, including the United Kingdom&#8217;s Bribery Act 2010. In many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are
    government entities; therefore, any dealings with these prescribers and purchasers may be subject to regulation under the FCPA. There is no certainty that all employees and third-party business partners (including our distributors, wholesalers, agents,
    contractors and other partners) will comply with anti-bribery laws. In particular, we do not control the actions of manufacturers and other third-party agents, although we may be liable for their actions. Violation of these laws may result in civil or
    criminal sanctions, which could include monetary fines, criminal penalties, and disgorgement of past profits, which could have an adverse impact on our business and financial condition<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to compliance with laws</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our operations are subject to additional healthcare laws.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operations are subject to additional healthcare laws, including federal and state anti-kickback laws, false claims laws, transparency
    laws, such as the federal Sunshine Act, and health information privacy and security laws, which are subject to change at any time. It is possible that governmental authorities will conclude that our business practices may not comply with current or
    future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. Penalties for violations of applicable healthcare laws and regulations may include significant civil, criminal and administrative
    penalties, damages, disgorgement, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and additional reporting requirements and oversight if we enter into a corporate integrity agreement
    or similar agreement to resolve allegations of non-compliance with these laws. In addition, violations may also result in reputational harm, diminished profits and future earnings.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating
    the protection of the environment and health and human safety, our business could be adversely affected.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and manufacturing activities involve the use of potentially harmful biological materials as well as materials,
    chemicals and various radioactive compounds that could be hazardous to human health and safety or the environment. We store most of these materials and various wastes resulting from their use at our facilities in Carlsbad, California pending ultimate
    use and disposal. We cannot completely eliminate the risk of contamination, which could cause:</div>

  <div><br />
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">interruption of our research, development and manufacturing efforts;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">injury to our employees and others;</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">environmental damage resulting in costly clean up; and</div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">liabilities under federal, state and local laws and regulations governing health and human safety, as well as the use, storage, handling and disposal of these materials
            and resultant waste products.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In such an event, we may be held liable for any resulting damages, and any liability could exceed our resources. Although we carry
    insurance for pollution liability in amounts and types that we consider commercially reasonable, the coverage or coverage limits of our insurance policies may not be adequate. If our losses exceed our insurance coverage, our financial condition would
    be adversely affected.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the
    risk of noncompliance.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Each year we are required to evaluate our internal control systems to allow management to report on and our Independent Registered Public
    Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act. As a result, we continue to incur additional expenses and divert our management&#8217;s time to comply with these regulations. In addition, if we cannot
    continue to comply with the requirements of Section 404 in a timely manner, we might be subject to sanctions or investigation by regulatory authorities, such as the SEC, the Public Company Accounting Oversight Board, or PCAOB, or The Nasdaq Global
    Select Market. Any such action could adversely affect our financial results and the market price of our common stock.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The SEC and other regulators have continued to adopt new rules and regulations and make additional changes to existing regulations that
    require our compliance. In July 2010, the Dodd-Frank Wall Street Reform and Protection Act, or the Dodd-Frank Act, was enacted, and in August 2022, the SEC adopted additional rules and regulations under the Dodd-Frank Act related to &#8220;say on pay&#8221; and
    proxy access. Stockholder activism, the current political environment and the current high level of government intervention and regulatory reform may lead to substantial new regulations and disclosure obligations, which has and may in the future lead
    to additional compliance costs and impact the manner in which we operate our business.</div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Risks related to taxes</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our ability to use our net operating loss carryovers and certain other tax attributes may be limited.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the Internal Revenue Code of 1986, as amended, or the Code, a corporation is generally allowed a deduction for net operating losses,
    or NOLs, carried over from a prior taxable year. Under the Code, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire. The same is true of other unused tax attributes, such as tax credits.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the current U.S. federal income tax law, U.S. federal NOLs generated in taxable years beginning after December 31, 2017 may be
    carried forward indefinitely, but the deductibility of such U.S. federal NOLs is limited to 80 percent of taxable income. It is uncertain if and to what extent various states will conform to current U.S. federal income tax law, and there may be periods
    during which states suspend or otherwise limit the use of NOLs for state income tax purposes.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition, under Sections 382 and 383 of the Code, and corresponding provisions of state law, if a corporation undergoes an &#8220;ownership
    change,&#8221; which is generally defined as a greater than 50 percentage-point cumulative change, by value, in its equity ownership over a three-year period, the corporation&#8217;s ability to use its pre-change NOL carryforwards and other pre-change tax
    attributes to offset its post-change income or taxes may be limited. We may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If an ownership change occurs
    and our ability to use our NOL carryforwards or other tax attributes is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. As a result of the Akcea Merger, we are subject to the separate
    return limitation year, or SRLY, rules. Under the SRLY rules, our utilization of Akcea&#8217;s pre-merger NOL and tax credit carryforwards is limited to the amount of income that Akcea contributes to our consolidated taxable income. The Akcea pre-merger tax
    attributes cannot be used to offset any of the income that Ionis contributes to our consolidated taxable income. In addition, at the state level, there may be periods during which the use of net operating losses is suspended or otherwise limited, which
    could accelerate or permanently increase state taxes owed.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Our future taxable income could be impacted by changes in tax laws, regulations and treaties.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A change in tax laws, treaties or regulations, or their interpretation, of any country in which we operate could materially affect us.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">We could be subject to additional tax liabilities.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to U.S. federal, state, local and foreign income taxes, sales taxes in the U.S., withholding taxes and transaction taxes in
    foreign jurisdictions. Significant judgment is required in evaluating our tax positions and our worldwide provision for taxes. During the ordinary course of business, there are many activities and transactions for which the ultimate tax determination
    is uncertain. In addition, our tax obligations and effective tax rates could be adversely affected by changes in the relevant tax, accounting and other laws, regulations, principles and interpretations, including those relating to income tax nexus, by
    recognizing tax losses or lower than anticipated earnings in jurisdictions where we have lower statutory rates and higher than anticipated earnings in jurisdictions where we have higher statutory rates, by changes in foreign currency exchange rates, or
    by changes in the valuation of our deferred tax assets and liabilities. We may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us. Although we believe our tax estimates
    are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for
    which a determination is made.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item1B"><!--Anchor--></a>Item 1B. Unresolved Staff Comments</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58</div>

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  </div>

  <div><br />
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  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item2"><!--Anchor--></a>Item 2. Properties</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of February 16, 2023, the
    following are the primary facilities in which we operate:</div>

  <div><br />
  </div>

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    <td style="width: 19.66%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property Description</div>
        </td>

    <td style="width: 2.18%; vertical-align: top;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Location</div>
        </td>

    <td style="width: 2.18%; vertical-align: top;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Square</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Footage</div>
        </td>

    <td style="width: 2.18%; vertical-align: top;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">or Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Initial Lease</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Term End Date</div>
        </td>

    <td style="width: 2.18%; vertical-align: top;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Lease</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Extension Options</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Laboratory and office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">176,300</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2037</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Two, five-year options to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office and meeting space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,000</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2037</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Two, five-year options to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Owned</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing support facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office and storage space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,700</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Boston, MA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,300</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2029</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">One, five-year option to extend</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Office space facility</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Carlsbad, CA</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,800</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leased</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None</div>
        </td>

  </tr>

  <tr>

    <td style="width: 19.66%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 12.55%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 9.77%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">341,700</div>
        </td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 10.38%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 14.52%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.18%; vertical-align: top; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 22.22%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold
    and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for
    net proceeds of approximately $200 million<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, with the potential to receive additional payments of up to $40 million plus funding to expand our R&amp;D campus</span>. We used a
    portion of the sale proceeds to extinguish our mortgage debt on our headquarters facilities of $51 million. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for two additional terms of five years each.
    In connection with the sale of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor to lease a new R&amp;D facility. The lessor will develop and construct a new building composed of research
    and development space and office space. We will design and construct tenant improvements to customize the facility&#8217;s interior space. Once this new facility is completed, our lease will commence.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside,
    California. The lessor will develop and construct a 217,000-square-foot building, composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the
    facility&#8217;s interior space. We will lease the facility for an initial term of 20 years and 3 months with options to extend the lease for two additional terms of 10 years each. The lease will commence when the lessor&#8217;s construction is complete and we are
    able to begin constructing tenant improvements.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe that our current and future facilities will be adequate for the foreseeable future.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item3"><!--Anchor--></a>Item 3. Legal Proceedings</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For details of legal proceedings, refer to Part IV, Item 15, Note 9, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Legal Proceedings,</span> in the Notes to the Consolidated Financial Statements.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item4"><!--Anchor--></a>Item 4. Mine Safety Disclosures</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br />
  </div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTII"><!--Anchor--></a>PART II</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a id="Item5"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 5. Market for Registrant</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Market Information and Dividends</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our common stock is traded publicly through The Nasdaq Global Select Market under the symbol &#8220;IONS.&#8221; As of February 16, 2023, there were approximately 483 stockholders of record of our common stock. Because many of our shares are held by brokers and other
    institutions on behalf of stockholders, we are unable to estimate the total number of stockholders represented by these record holders.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have never paid dividends and do not anticipate paying any dividends in the foreseeable future.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Graph (1)</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Set forth below is a table and chart comparing the total return on an indexed basis of $100 invested on December 31, 2017 in our common
    stock, the Nasdaq Composite Index (total return) and the Nasdaq Biotechnology Index. The total return assumes reinvestment of dividends.</div>

  <div><br />
  </div>

  <div style="text-align: center;"><img width="709" height="583" src="image8.jpg" alt="graphic" /></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*&#160; $100 invested on December 31, 2017 in stock or index, including reinvestment of dividends. Fiscal year ending December 31.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Among Ionis Pharmaceuticals, Inc., the Nasdaq Composite Index,</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">and the Nasdaq Biotechnology Index</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-17</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-18</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-19</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-20</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-21</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Dec-22</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis Pharmaceuticals, Inc.</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">107.48</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120.10</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112.41</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60.50</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.09</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Composite Index</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97.16</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">132.81</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">192.47</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">235.15</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">158.65</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Nasdaq Biotechnology Index</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.00</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">91.14</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">114.02</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144.15</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144.18</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129.59</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This section is not &#8220;soliciting material,&#8221; is not deemed &#8220;filed&#8221; with the SEC, is not subject to the liabilities of Section 18 of the Exchange Act and is not to be
            incorporated by reference in any of our filings under the Securities Act or the Exchange Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item6"><!--Anchor--></a>Item 6. Selected Financial Data</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to our financial data contained within Part II, Item 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Management&#8217;s Discussion and Analysis</span>, our financial statements and within other parts of this document.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a id="Item7"><!--Anchor--></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Item 7. Management</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Discussion and Analysis of Financial Condition and Results of Operations</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This financial review presents our operating results for each of the two years in the period ended December 31, 2022, and our financial condition as of December 31, 2022.
    Refer to our 2021 Form 10-K for our results of operations for 2021 compared to 2020. Except for the historical information contained herein, the following discussion contains forward-looking statements that are subject to known and unknown risks,
    uncertainties and other factors that may cause our actual results to differ materially from those expressed or implied by such forward-looking statements. We discuss such risks, uncertainties and other factors throughout this report and specifically
    under Item 1A of Part I of this report, &#8220;Risk Factors.&#8221; In addition, the following review should be read in conjunction with the information presented in our consolidated financial statements and the related notes to our consolidated financial
    statements included in Item 8 of Part II of this report.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Overview</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As noted in our Business Overview in Part I of this report, we were founded over 30 years ago to deliver innovative new medicines for
    diseases with great medical need. Today, we are building on our advancements in RNA-targeted therapeutics with a vision to be the leader in genetic medicines. We believe our genetic medicines have the potential to pioneer new markets, change standards
    of care and transform the lives of people with devastating diseases. We currently have three marketed medicines: SPINRAZA, TEGSEDI and WAYLIVRA. We also have two medicines, eplontersen and tofersen, that will add to our commercial portfolio this year,
    assuming positive regulatory outcomes. In addition to our commercial medicines and medicines under regulatory review, we have a rich innovative late- and mid-stage pipeline primarily focused on our leading cardiovascular and neurology franchises. We
    currently have seven medicines in Phase 3 development. Refer to Part I, Item 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span>, for further details on our business and key developments
    in our medicines.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Results of Operations</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Below we have included our results of operations for 2022 compared to 2021. Refer to our 2021 Form 10-K for our results of operations for
    2021 compared to 2020. The following table provides selected summary information from our consolidated statements of operations for 2022 and 2021 (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">587.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">810.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">997.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">840.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(410.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(30.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(269.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash, cash equivalents and short-term investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,986.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,115.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">61</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue for 2022 was $587.4 million compared to $810.5 million in 2021 and was comprised of the following (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">242.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">267.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">30.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total commercial revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">303.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">342.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization from upfront payments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">License fees</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">291.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other services</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Collaborative agreement revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">207.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">468.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 27pt; margin-left: 45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">284.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">468.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 27pt; margin-left: 81pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">587.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">810.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 2022 revenue continued to be derived from diverse sources, with just over half coming from commercial products and the balance from
    numerous partnered programs. SPINRAZA royalties, the largest contributor to our commercial revenue, increased each quarter in 2022. Total SPINRAZA product sales increased six percent in the fourth quarter of 2022 compared to the third quarter of 2022
    and also increased four percent compared to the same quarter in 2021. The increases were driven by stabilization in the U.S. and growth in Asian markets, partially offset by competition in Europe. Total SPINRAZA product sales decreased six percent
    year-over-year driven by foreign currency exchange and competition in Europe, partially offset stabilization in the U.S. and growth in Asian markets. Our TEGSEDI and WAYLIVRA revenue was also lower year-over-year due to the shift to distribution fees
    in 2021.</div>

  <div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our R&amp;D revenue for 2022 included $112 million from Biogen for advancing several neurology disease programs, $77 million from
    AstraZeneca for its share of the global Phase 3 development costs for eplontersen and $64 million from Roche for licensing and advancing IONIS-FB-L<sub>Rx</sub>, among other partnered payments. R&amp;D revenue was higher in 2021 compared to 2022 driven
    primarily by the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to jointly develop and commercialize eplontersen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Eplontersen Collaboration with AstraZeneca</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our financial results for the year ended December 31, 2022 reflected the cost-sharing provisions related to our collaboration with
    AstraZeneca to develop and commercialize eplontersen for the treatment of ATTR. Under the terms of the collaboration agreement, AstraZeneca is currently paying 55 percent of the costs associated with the ongoing global Phase 3 development program.
    Because we are leading and conducting the Phase 3 development program, we are recognizing as R&amp;D revenue the 55 percent of cost-share funding AstraZeneca is responsible for, net of our share of AstraZeneca&#8217;s development expenses, in the same period
    we incur the related development expenses. In the year ended December 31, 2022, we earned $77 million in joint development revenue and recorded $147M of R&amp;D expenses related to Phase 3 development expenses under this collaboration.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As AstraZeneca is responsible for the majority of the medical affairs and commercial costs in the U.S. and all costs associated with
    bringing eplontersen to market outside the U.S., we are recognizing cost-share funding we receive from AstraZeneca related to these activities as a reduction of our medical affairs and commercialization expenses, which we classify as R&amp;D and
    selling, general and administrative, or SG&amp;A, expenses, respectively. In the year ended December 31, 2022, we recognized $2.0 million and $2.6 million of medical affairs expenses and commercialization expenses for eplontersen, respectively, net of
    cost-share funding from AstraZeneca. We expect our medical affairs and commercialization expenses to increase as eplontersen advances toward the market under our collaboration with AstraZeneca.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of the financial impacts on our statement of operations for the year ended December 31, 2022 of the joint
    development activities under our eplontersen collaboration with AstraZeneca:</div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Expenses</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses were as follows (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">897.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">696.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">897.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">719.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total operating expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">997.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">840.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our operating expenses, excluding non-cash compensation expense related to equity awards, increased in 2022 compared to 2021. Our R&amp;D
    expenses increased in 2022 compared to 2021 due to our investments in advancing our late-stage pipeline, including the expanded number of Phase 3 studies we are conducting, which doubled from three to six studies in 2021. Our R&amp;D expenses also
    increased in 2022 compared to 2021 due to $80 million that we recognized in 2022 for licensing Metagenomi&#8217;s gene editing technologies. Our SG&amp;A expenses decreased in 2022 compared to 2021 as a result of savings we realized from integrating Akcea
    and restructuring our commercial operations for TEGSEDI and WAYLIVRA, partially offset by the increase in expenses related to our go-to-market activities for eplontersen, donidalorsen and olezarsen.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our non-cash compensation expense related to equity awards decreased in 2022 compared to 2021 as a result of the decrease in our stock
    price in 2022 compared to 2021 and reduced headcount due to restructuring our commercial operations in 2021. We anticipate our non-cash compensation expense related to equity awards to increase in 2023 due to increased headcount and an increase in our
    stock price when we granted annual equity awards to our employees in January 2023 compared to January 2022.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To analyze and compare our results of operations to other similar companies, we believe it is important to exclude non-cash compensation
    expense related to equity awards from our operating expenses. We believe non-cash compensation expense related to equity awards is not indicative of our operating results or cash flows from our operations. Further, we internally evaluate the
    performance of our operations excluding it.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Cost of Sales</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, which consisted of manufacturing costs, including certain
      fixed costs, transportation and freight, indirect overhead costs associated with the manufacturing and distribution of TEGSEDI and WAYLIVRA and certain associated period costs.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales were as follows (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total cost of sales</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">63</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Research, Development and Patent Expenses</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses consist of expenses for drug discovery, drug development, manufacturing and development
    chemistry and R&amp;D support expenses.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on research, development and patent expenses (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">759.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">547.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">759.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">555.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research, development and patent expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">833.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">643.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Drug Discovery</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use our proprietary technologies to generate information about the function of genes and to determine the value of genes as drug
    discovery targets. We use this information to direct our own drug discovery research, and that of our partners. Drug discovery is also the function that is responsible for advancing our core technology. This function is also responsible for making
    investments in complementary technologies to expand the reach of our technologies.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our drug discovery expenses were as follows (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">181.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">136.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug discovery expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">197.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">158.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Drug discovery expenses, excluding non-cash compensation expense related to equity awards, increased in 2022 compared to 2021 primarily
    due to $80 million that we recognized in 2022 for licensing Metagenomi&#8217;s gene editing technologies. In 2021, we incurred certain licensing expenses, including $35 million for licensing Bicycle Therapeutics&#8217; peptide technology.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Drug Development</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth drug development expenses, including expenses for our marketed medicines and those in Phase 3 development
    for which we have incurred significant costs (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">103.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Olezarsen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Donidalorsen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">ION363</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other development projects</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">129.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Development overhead expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug development, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">426.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">311.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">37.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total drug development expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">457.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">349.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div>

    </div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our development expenses, excluding non-cash compensation expense related to equity awards, increased in 2022 compared to 2021 primarily
    due to our advancing late-stage pipeline, including the expanded number of Phase 3 studies we are conducting, which doubled over the course of 2021 from three to six studies.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may conduct multiple clinical trials on a drug candidate, including multiple clinical trials for the various indications we may be
    studying. Furthermore, as we obtain results from trials, we may elect to discontinue clinical trials for certain drug candidates in certain indications in order to focus our resources on more promising drug candidates or indications. Our Phase 1 and
    Phase 2 programs are clinical research programs that fuel our Phase 3 pipeline. When our medicines are in Phase 1 or Phase 2 clinical trials, they are in a dynamic state in which we may adjust the development strategy for each medicine. Although we may
    characterize a medicine as &#8220;in Phase 1&#8221; or &#8220;in Phase 2,&#8221; it does not mean that we are conducting a single, well-defined study with dedicated resources. Instead, we allocate our internal resources on a shared basis across numerous medicines based on
    each medicine&#8217;s particular needs at that time. This means we are constantly shifting resources among medicines. Therefore, what we spend on each medicine during a particular period is usually a function of what is required to keep the medicines
    progressing in clinical development, not what medicines we think are most important. For example, the number of people required to start a new study is large, the number of people required to keep a study going is modest and the number of people
    required to finish a study is large. However, such fluctuations are not indicative of a shift in our emphasis from one medicine to another and cannot be used to accurately predict future costs for each medicine. And, because we always have numerous
    medicines in preclinical and varying stages of clinical research, the fluctuations in expenses from medicine to medicine, in large part, offset one another. If we partner a medicine, it may affect the size of a trial, its timing, its total cost and the
    timing of the related costs.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Medical Affairs</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our medical affairs function is responsible for managing
      publications planning, funding and coordinating investigator-sponsored trials and communicating scientific and clinical information to healthcare providers, medical professionals and patients</span>.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our medical affairs expenses were as follows (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Medical affairs expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total medical affairs expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Medical affairs expenses, excluding non-cash compensation
      expense related to equity awards, increased in 2022 compared to 2021 due to increased costs we incurred as we built our medical affairs function to support our late-stage pipeline</span>.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">Manufacturing and Development Chemistry</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenditures in our manufacturing and development chemistry function consist primarily of personnel costs, specialized chemicals for
    oligonucleotide manufacturing, laboratory supplies and outside services. Our manufacturing and development chemistry function is responsible for providing drug supplies to drug development and our collaboration partners. Our manufacturing procedures
    include testing to satisfy good laboratory and good manufacturing practice requirements.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our manufacturing and development chemistry expenses were as follows (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses, excluding non-cash compensation expense related to equity
            awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total manufacturing and development chemistry expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Manufacturing and development chemistry expenses, excluding
      non-cash compensation expense related to equity awards, increased in 2022 compared to 2021 due to increased R&amp;D-related manufacturing costs we incurred in preparation for our near-term commercial launches of eplontersen, olezarsen and
      donidalorsen. Refer to the section titled, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Manufacturing</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in
      Part I, Item 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Business</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for further details on the
      activities and types of costs we incur in our manufacturing process.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-decoration: underline;">R&amp;D Support</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our research, development and patent expenses, we include support costs such as rent, repair and maintenance for buildings and
    equipment, utilities, depreciation of laboratory equipment and facilities, amortization of our intellectual property, informatics costs, procurement costs and waste disposal costs. We call these costs R&amp;D support expenses.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on R&amp;D support expenses (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Personnel costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Occupancy</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Patent expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Insurance</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software and licenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total R&amp;D support expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64.0</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D support expenses, excluding non-cash compensation expense related to equity awards, increased in 2022 compared to 2021. The
    increase was primarily related to increased occupancy and personnel costs to support advancing our pipeline and our technology. In October 2022, we executed a sale and leaseback transaction for our headquarters in Carlsbad, California. As a result,
    beginning in the fourth quarter of 2022, our occupancy costs increased because we began incurring rent expense for these facilities.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Selling, General and Administrative Expenses</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative, or SG&amp;A, expenses include personnel and outside costs associated with the pre-commercialization
    and commercialization activities for our medicines and costs to support our company, our employees and our stockholders including, legal, human resources, investor relations and finance. Additionally, we include in selling, general and administrative
    expenses such costs as rent, repair and maintenance of buildings and equipment, depreciation and utilities costs that we need to support the corporate functions listed above. We also include fees we owe under our in-licensing agreements related to
    SPINRAZA.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on SG&amp;A expenses (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative expenses, excluding non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">138.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Restructuring expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses, excluding non-cash compensation related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">153.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash compensation expense related to equity awards</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total selling, general and administrative expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">150.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">186.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SG&amp;A expenses, excluding non-cash compensation expense related to equity awards, decreased in 2022 compared to 2021 due to operating
    efficiencies achieved from restructuring our commercial operations for TEGSEDI and WAYLIVRA, partially offset by increased expenses for our go-to-market preparations for our near-term commercial opportunities. Non-cash compensation expense related to
    equity awards decreased in 2022 compared to 2021 as a result of restructuring our commercial operations for TEGSEDI and WAYLIVRA in 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">66</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Investment Income</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investment income for 2022
    was $25.3 million compared to $10.0
    million for 2021. The increase in investment income was primarily due to an increase in interest rates during 2022 compared to 2021.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Interest Expense</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information on interest expense (in millions):</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible senior notes:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash amortization of the debt discounts and debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense payable in cash</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest on mortgage for primary R&amp;D and manufacturing facilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total interest expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9.3</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Gain (Loss) on Investments</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded a $7.3 million loss
    on investments for 2022 compared to a $10.1 million gain on investments for 2021. The period-over-period fluctuation in our gain (loss) on
    investments was primarily driven by changes in fair value of our investments in publicly traded biotechnology companies<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Gain on Sale of Real Estate</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold
    and leased back the facilities at our headquarters location in Carlsbad, California and will sell, subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our headquarters for
    a total purchase price of $263.4 million and recorded a gain of $150.1 million in the fourth quarter of 2022, resulting in income tax expense of $8.8 million.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Expense</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2022, we recorded a $7.7 million net expense to settle a litigation claim.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, as a result of a debt offering and debt repurchase, we recorded an $8.6 million loss on early retirement of debt, reflecting the
    early retirement of a portion of our 1% Notes. The loss on the early retirement of our debt is the difference between the amount we paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Income Tax Expense (Benefit)</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded an income tax expense of $11.7 million for 2022 compared to an income tax benefit of $0.6 million for 2021. Beginning in 2022,
    the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to capitalize and amortize research and development expenditures pursuant to Internal Revenue Code, or IRC, Section 174. Our 2022 tax expense relates primarily to the impact of this new law
    and to federal and state tax on the gain from the sale of our headquarters facilities that closed in October 2022.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Net Loss and Net Loss per Share</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generated a net loss of $269.7
    million for 2022 compared to $28.6
    million for 2021. Our net loss increased for 2022 compared to 2021 primarily due to decreased revenue and increased expenses year-over-year,
    as discussed in the revenue and expenses sections, respectively<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share for 2022
    were each $1.90. Basic and diluted net loss per share for 2021 were each $0.20.</div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67</div>

    </div>

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  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Liquidity and Capital Resources</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We have financed our operations primarily from research and
      development collaborative agreements. </span>We also finance our operations from commercial revenue from SPINRAZA royalties and TEGSEDI and WAYLIVRA commercial revenue. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From
      our inception through December 31, </span>2022, we have earned approximately $6.4 billion<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in revenue. We have also financed our operations through the sale of our equity securities and the
      issuance of long-term debt. From the time we were founded through December 31, </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have raised net proceeds of approximately $</span>2.0&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">billion from the sale of our equity securities. Additionally, we borrowed approximately $</span>2.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion under long-term debt arrangements to finance a portion of our operations over the same time period.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our cash, cash equivalents and short-term investments, debt
      obligations and working capital decreased from 2021 to 2022. In 2021, we issued $632.5 million of 0% Notes (due in April 2026) and we used a portion of the proceeds to repurchase $247.9 million of our 1% Notes in April 2021. We paid the remaining
      principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021. In 2022, we sold the facilities and related land at our headquarters for a total purchase price of $263.4 million and used a portion of the proceeds to
      extinguish our mortgage debt on these facilities of $51.3 million. At </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we had $2.0 billion of cash and short-term investments on hand. We believe our cash and short-term investment balance is sufficient to fund our operations in the short-term and in the longer-term. </span>In 2022,
    our working capital decreased because our cash and investments decreased as discussed above.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our contractual obligations as of December 31, 2022. The table provides a breakdown of when obligations become due. We provide a more detailed description of the major components of our debt in <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note 4, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Obligations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Payments Due by Period</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(in millions)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(selected balances described below)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 1 year</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 1 year</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0% Notes (principal payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125% Notes (principal and interest payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">549.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building mortgage payments (principal and interest payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating leases</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">299.6</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">279.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations (principal and interest payable)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,493.9</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.4</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,472.5</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our contractual obligations consist primarily of our convertible debt. In addition, we also have a facility mortgage, facility leases,
    equipment financing arrangements and other obligations. Due to the uncertainty with respect to the timing of future cash flows associated with our unrecognized tax benefits, we are unable to make reasonably reliable estimates of the period of cash
    settlement with the respective taxing authorities. Therefore, we have excluded our gross unrecognized tax benefits from our contractual obligations table above. We have not entered into, nor do we currently have, any off-balance sheet arrangements (as
    defined under SEC rules<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">).</span></div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Convertible Debt and Call Spread</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Refer to our Convertible Debt and Call Spread accounting
      policies in Part IV, Item 15, Note 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and Note 4, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, in the Notes to our consolidated financial statements for the significant terms of each convertible debt instrument.</span></div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Operating Facilities</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the Notes to our consolidated financial statements for further details on our operating facilities.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Operating Leases</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the Notes to our consolidated financial statements for further details on our operating leases<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">68</div>

    </div>

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  </div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Royalty Revenue Monetization</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and pelacarsen
    royalties we are entitled to under our agreements with Biogen and Novartis, respectively. Refer to <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Part IV, Item 15, </span>Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, in the Notes to our consolidated financial statements for further details on this agreement.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Other Obligations</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to contractual obligations, we had outstanding purchase orders as of December 31, 2022 for the purchase of services, capital
    equipment and materials as part of our normal course of business.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We may enter into additional collaborations with partners that could provide for additional revenue to us and we may incur additional cash
    expenditures related to our obligations under any of the new agreements we may enter into. We currently intend to use our cash, cash equivalents and short-term investments to finance our activities. However, we may also pursue other financing
    alternatives, like issuing additional shares of our common stock, issuing debt instruments, refinancing our existing debt, or securing lines of credit. Whether we use our existing capital resources or choose to obtain financing will depend on various
    factors, including the future success of our business, the prevailing interest rate environment and the condition of financial markets generally.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Critical Accounting Estimates</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. As such, we make
    certain estimates, judgments and assumptions that we believe are reasonable, based upon the information available to us. These judgments involve making estimates about the effect of matters that are inherently uncertain and may significantly impact our
    quarterly or annual results of operations and financial condition. Each quarter, our senior management reviews the development, selection and disclosure of such estimates with the audit committee of our board of directors. In the following paragraphs,
    we describe the specific risks associated with these critical accounting estimates and we caution that future events rarely develop exactly as one may expect, and that best estimates may require adjustment. Our significant accounting policies are
    outlined in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span>, in the Notes to the Consolidated Financial Statements.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are our significant accounting estimates, which we believe are the most critical to aid in fully understanding and
    evaluating our reported financial results:</div>

  <div><br />
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Assessing the propriety of revenue recognition and associated deferred revenue; and</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the appropriate cost estimates for unbilled preclinical studies and clinical development activities</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are descriptions of our critical accounting estimates.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Revenue Recognition</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn revenue from several sources. The judgements and estimates we make vary between each source of our revenue. At contract inception,
    we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the
    commercial success of such activities and therefore within the scope of Accounting Standards Codification, or ASC, Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>,
    or ASC 808. For collaboration arrangements within the scope of ASC 808 that contain multiple elements, we first determine which elements of the collaboration reflect a vendor-customer relationship and are therefore within the scope of ASC 606, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span>. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we consistently
    apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of the critical accounting estimates we make with respect to our revenue.</div>

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  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaborative agreements</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize R&amp;D revenue from numerous collaboration agreements. Our collaboration agreements typically contain multiple elements, or
    performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services, and manufacturing services. Upon entering into a collaboration agreement, we are required to make the following judgements:</div>

  <div><br />
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Identifying the performance obligations contained in the agreement</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our assessment of what constitutes a separate performance
      obligation requires us to apply judgement.</span> Specifically, we have to identify which goods and services we are required to provide under the contract are distinct.</div>

  <div><br />
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Determining the transaction price, including any variable consideration</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To determine the transaction price, we review the amount of consideration we are eligible to earn under the agreement. We do not typically
    include any payments we may receive in the future in our initial transaction price since the payments are typically not probable because they are contingent upon certain future events. We reassess the total transaction price at each reporting period to
    determine if we should include additional payments in the transaction price that have become probable.</div>

  <div><br />
  </div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Allocating the transaction price to each of our performance obligations</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we allocate the transaction price to more than one performance obligation, we make estimates of the relative stand-alone selling
    price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. The estimate of the relative stand-alone selling price requires us in some cases to make significant judgements. For example, when we
    deliver a license at the start of an agreement, we use valuation methodologies, such as the relief from royalty method, to value the license. Under this method we are required to make estimates including: future sales, royalties on future product
    sales, contractual milestones, expenses, income taxes and discount rates. Additionally, when we estimate the selling price for R&amp;D services, we make estimates, including: the number of internal hours we will spend on the services, the cost of work
    we and third parties will perform and the cost of clinical trial material we will use.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The R&amp;D revenue we recognize each period is comprised of several types of revenue, including amortization from upfront payments,
    milestone payments, license fees and other services that are recognized immediately or amortized over the period in which we satisfy our performance obligation. Each of these types of revenue require us to make various judgements and estimates.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">R&amp;D Services with Upfront Payments</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize revenue from the amortization of upfront payments as we perform R&amp;D services. We use an input method to estimate the
    amount of revenue to recognize each period. This method requires us to make estimates of the total costs we expect to incur to complete our R&amp;D services performance obligation or the total length of time it will take us to complete our R&amp;D
    services performance obligation. If we change our estimates, we may have to adjust our revenue.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Milestone Payments</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When recognizing revenue related to milestone payments we typically make the following judgements and estimates:</div>

  <div><br />
  </div>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the milestone payment is probable (discussed in detail above under &#8220;Determining the<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">
              transaction price, including any variable consideration&#8221;</span>); and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the milestone payment relates to services we are performing or if our partner is performing the services:</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we are performing services, we recognize revenue over our estimated period of performance in a similar manner to the amortization of upfront payments (discussed above
            under &#8220;R&amp;D Services with Upfront Payments&#8221;).</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the milestone event and we do not have
            a performance obligation.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">License Fees</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we grant a license for a medicine in clinical
      development, we generally recognize as R&amp;D revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. Refer to Part IV, Item 15, Note 1, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, for our revenue
      recognition policy. We discuss the estimates we make related to the relative stand-alone selling price of a license in detail above under &#8220;Allocating the transaction price to each of our performance obligations.&#8221;</span></div>

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  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Estimated Liability for Clinical Development Costs</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, a hypothetical 10 percent increase in our liability for preclinical and clinical development costs would have
    resulted in an increase in our loss before income tax benefit and accrued liabilities of approximately $11.6 million.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item7A"><!--Anchor--></a>Item 7A. Quantitative and Qualitative Disclosures About Market Risk</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are exposed to changes in interest rates primarily from
      our investments in certain short-term investments. We primarily invest our excess cash in highly liquid short-term investments of the U.S. Treasury and reputable financial institutions, corporations, and U.S. government agencies with strong credit
      ratings. We typically hold our investments for the duration of the term of the respective instrument. We do not utilize derivative financial instruments, derivative commodity instruments or other market risk sensitive instruments, positions or
      transactions to manage exposure to interest rate changes. Accordingly, we believe that, while the securities we hold are subject to changes in the financial standing of the issuer of such securities, we were not subject to any material risks arising
      from changes in interest rates, foreign currency exchange rates, commodity prices, equity prices or other market changes that affect market risk sensitive instruments as of December 31, 2022 and will not be subject to any material risks arising from
      these changes in the foreseeable future</span>.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item8"><!--Anchor--></a>Item 8. Financial Statements and Supplementary Data</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We filed our consolidated financial statements and supplementary data required by this item as exhibits hereto, and listed them under Item
    15(a)(1) and (2), and incorporate them herein by reference.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9"><!--Anchor--></a>Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">None.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9A"><!--Anchor--></a>Item 9A. Controls and Procedures</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Disclosure Controls and Procedures</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We maintain disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as
    amended, or Exchange Act) that are designed to ensure that information we are required to disclose in our Exchange Act reports is recorded, processed, summarized and reported within the time periods specified in the SEC&#8217;s rules and forms, and that such
    information is accumulated and communicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. We designed and evaluated our disclosure controls
    and procedures recognizing that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance and not absolute assurance of achieving the desired control objectives.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of the end of the period covered by this report on Form 10-K, we carried out an evaluation of our disclosure controls and procedures
    under the supervision of, and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on our evaluation, our Chief Executive Officer and Chief Financial Officer concluded that our disclosure
    controls and procedures were effective as of December 31, 2022.</div>

  <div><br />
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  <div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Management</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s Report on Internal Control over Financial Reporting</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Exchange
    Act Rules 13a-15(f). Our internal control over financial reporting is a process designed under the supervision of our Chief Executive Officer and Chief Financial Officer to provide reasonable assurance regarding the reliability of financial reporting
    and the preparation of our financial statements for external purposes in accordance with U.S. generally accepted accounting principles.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, we
    assessed the effectiveness of our internal control over financial reporting based on the criteria for effective internal control over financial reporting under the 2013 &#8220;Internal Control&#8212;Integrated Framework,&#8221; issued by the Committee of Sponsoring
    Organizations, or COSO, of the Treadway Commission, under the supervision of, and with the participation of our management, including our Chief Executive Officer and Chief Financial Officer. Based on that assessment, our management concluded that we
    maintained effective internal control over financial reporting as of December 31, 2022.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ernst &amp; Young LLP, an independent registered public accounting firm, audited the effectiveness of our internal control over financial
    reporting as of December 31, 2022, as stated in their attestation report, which is included elsewhere herein.</div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Changes in Internal Control over Financial Reporting</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The above assessment did not identify any change in our internal control over financial reporting that occurred during our latest fiscal
    quarter and that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the Stockholders and Board of Directors of Ionis Pharmaceuticals, Inc.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on Internal Control over Financial Reporting</div>

  <div><br />
  </div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have audited Ionis Pharmaceuticals, Inc.&#8217;s internal control over financial reporting as of December 31, 2022, based on criteria
    established in Internal Control&#8212;Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). In our opinion, Ionis Pharmaceuticals, Inc. (the Company) maintained, in all
    material respects, effective internal control over financial reporting as of December 31, 2022, based on the COSO criteria.</div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the
    consolidated balance sheets of the Company as of December 31, 2022 and 2021, the related consolidated statements of operations, comprehensive loss, stockholders&#8217; equity and cash flows for each of the three years in the period ended December 31, 2022,
    and the related notes and our report dated February 22, 2023 expressed an unqualified opinion thereon.</div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis for Opinion</div>

  <div><br />
  </div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The Company&#8217;s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the
    effectiveness of internal control over financial reporting included in the accompanying Management&#8217;s Report on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the Company&#8217;s internal control over financial
    reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the
    Securities and Exchange Commission and the PCAOB.</div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to
    obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects.</div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness
    exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable
    basis for our opinion.</div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Definition and Limitations of Internal Control Over Financial Reporting</div>

  <div><br />
  </div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A company&#8217;s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of
    financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company&#8217;s internal control over financial reporting includes those policies and procedures that (1)
    pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit
    preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company; and (3)
    provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company&#8217;s assets that could have a material effect on the financial statements.</div>

  <div style="text-align: justify; margin-bottom: 8pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections
    of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ Ernst &amp; Young LLP</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">San Diego, California</div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>

  <div><br />
  </div>

  <div><br />
  </div>

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  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9B"><!--Anchor--></a>Item 9B. Other Information</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item9C"><!--Anchor--></a>Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Not applicable.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTIII"><!--Anchor--></a>PART III</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item10"><!--Anchor--></a>Item 10. Directors, Executive Officers and Corporate Governance</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We incorporate by reference the information required by this
      Item with respect to directors and the Audit Committee from the information under the caption &#8220;ELECTION OF DIRECTORS,&#8221; including in particular the information under &#8220;Nominating, Governance and Review Committee&#8221; and &#8220;Audit Committee,&#8221; contained in our
      definitive Proxy Statement, which we will file with the Securities and Exchange Commission within 120 days after the end of the fiscal year ended </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Proxy Statement.</span></div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We include information concerning our executive officers in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Information about our Executive Officers</span>, in this report on the Form 10-K in Item 1 titled &#8220;Business.&#8221;</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the required information concerning our Code of Ethics from the information under the caption &#8220;Code of Ethics
    and Business Conduct&#8221; contained in the Proxy Statement. Our Code of Ethics and Business Conduct is posted on our website at www.ionispharma.com<sup>(1)</sup>. We intend to disclose future amendments to, or waivers from, our Code of Ethics and Business
    Conduct on our website.</div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

  <div>
    <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; text-align: right;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Any information that is included on or linked to our website is not part of this Form 10-K.</div>
          </td>

  </tr>


</table>
  </div>

  <div><br />
  </div>

  <div style="text-align: left; text-indent: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Delinquent Section 16(a) Reports</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Item 1, Part I of this Report contains information concerning our executive officers. We incorporate by reference the information required
    by this Item concerning compliance with Section 16(a) of the Exchange Act from the information under the caption &#8220;Delinquent Section 16(a) Reports&#8221; contained in the Proxy Statement.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item11"><!--Anchor--></a>Item 11. Executive Compensation</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the caption &#8220;EXECUTIVE COMPENSATION,&#8221;
    &#8220;Compensation Committee Interlocks and Insider Participation&#8221; and &#8220;COMPENSATION COMMITTEE REPORT&#8221; contained in the Proxy Statement.</div>

  <div><br />
  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74</div>

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  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item12"><!--Anchor--></a>Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the captions &#8220;SECURITY OWNERSHIP OF CERTAIN
    BENEFICIAL OWNERS AND MANAGEMENT&#8221; contained in the Proxy Statement.</div>

  <div><br />
  </div>

  <div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Securities Authorized for Issuance under Equity Compensation Plans</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table sets forth information regarding outstanding options and shares reserved for future issuance under our equity
    compensation plans as of December 31, 2022.</div>

  <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 41.45%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Plan Category</div>
        </td>

    <td style="width: 1%; vertical-align: bottom;">&#160;</td>

    <td style="width: 19.85%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of Shares to</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">be Issued Upon Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Outstanding Options</div>
        </td>

    <td style="width: 0.75%; vertical-align: bottom;">&#160;</td>

    <td style="width: 17.48%; vertical-align: bottom; border-bottom: #000000 2px solid;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exercise Price of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Outstanding Options</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining Available</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">for Future Issuance</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 41.45%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity compensation plans approved by stockholders (a)</div>
        </td>

    <td style="width: 1%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 19.85%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,970,226</div>
        </td>

    <td style="width: 0.75%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 2.87%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td style="width: 14.61%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.57</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 2px solid; background-color: #CCEEFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,158,690</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(b)</div>
        </td>

  </tr>

  <tr>

    <td style="width: 41.45%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -10pt; margin-left: 10pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td style="width: 1%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 19.85%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,970,266</div>
        </td>

    <td style="width: 0.75%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 2.87%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td style="width: 14.61%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.57</div>
        </td>

    <td style="width: 0.87%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 16.36%; vertical-align: bottom; border-bottom: #000000 4px double; background-color: #FFFFFF;">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,158,690</div>
        </td>

    <td style="width: 2.24%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

  </tr>


</table>
  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

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  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(a)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consists of five Ionis plans: 1989 Stock Option Plan, Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, 2011 Equity Incentive Plan, 2020 Equity
            Incentive Plan and Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>
  <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(b)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Of these shares, 492,176 were available for purchase under the ESPP as of December 31, 2022.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For additional details about our equity compensation plans, including a description of each plan, refer to Part IV, Item 15, Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217; Equity</span>, in the Notes to the Consolidated Financial Statements.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item13"><!--Anchor--></a>Item 13. Certain Relationships and Related Transactions, and Director Independence</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the captions &#8220;Independence of the Board of
    Directors&#8221; and &#8220;Certain Relationships and Related Transactions&#8221; contained in the Proxy Statement.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item14"><!--Anchor--></a>Item 14. Principal Accountant Fees and Services</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporate by reference the information required by this item to the information under the caption &#8220;Ratification of Selection of
    Independent Auditors&#8221; contained in the Proxy Statement.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="PARTIV"><!--Anchor--></a>PART IV</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Item15"><!--Anchor--></a>Item 15. Exhibits, Financial Statement Schedules</div>

  <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(1) Index to Financial Statements</div>

  <div style="text-align: justify; text-indent: -36pt; margin-left: 72pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We submitted the consolidated financial statements required by this item in a separate section beginning on page F-1 of this Report.</div>

  <div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(2) Index to Financial Statement Schedules</div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We omitted these schedules because they are not required, or are not applicable, or the required information is shown in the consolidated
    financial statements or notes thereto.</div>

  <div style="text-align: left; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; text-indent: -36pt; margin-left: 72pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(a)(3) Index to Exhibits</div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>

    </div>

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  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO EXHIBITS</div>

  <div><br />
  </div>

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    <td style="width: 7.41%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit Number</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description of Document</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000119312520235408/d75253dex21.htm">Agreement and Plan of Merger, dated as of August 30, 2020, among Akcea Therapeutics, Inc., Ionis Pharmaceuticals, Inc. and Avalanche Merger Sub, Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed August 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.1</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit3_1.htm">Amended and Restated Certificate of Incorporation filed June 19, 1991</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.2</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036114017588/formdef14a.htm">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an exhibit to the Registrant&#8217;s Notice of Annual Meeting and Proxy Statement, for the 2014 Annual Meeting of Stockholders, filed on April 25, 2014 and incorporated
              herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.3</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036115045083/ex3_1.htm">Certificate of Amendment to Restated Certificate of Incorporation</a><span style="font-size: 12pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 18, 2015 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3.4</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036121010402/brhc10022399_ex3-1.htm">Amended and Restated Bylaws</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Current Report on Form 8-K filed March 29, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.1</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit4-11.htm">Description of the Registrant&#8217;s Securities</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.2</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000091205700053343/a2032851zex-4_2.txt">Certificate of Designation of the Series C Junior Participating Preferred Stock</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to Registrant&#8217;s Current Report on Form 8-K filed December 13, 2000 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit4_2.htm">Specimen Common Stock Certificate</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.4</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119023019/ex4_1.htm">Indenture, dated as of December 19, 2019, by and between the Registrant and U.S. Bank National Association, as trustee, including Form of 0.125 percent
              Convertible Senior Note due 2024</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 23, 2019 and incorporated herein by
              reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.5</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex41.htm">Indenture, dated as of April 12, 2021, by and between the Registrant and U.S. Bank National Association, as trustee, including Form of 0 percent
              Convertible Senior Note due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.6</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119022393/ex99_1.htm">Form of Exchange and/or Subscription Agreement for Convertible Senior Notes due 2024</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 12, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119022393/ex99_2.htm">Form of Convertible Note Hedge Transactions Confirmation</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;"> for Convertible
                Senior Notes due 2024</span>, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 12, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.8</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex101.htm">Form of Convertible Note Hedge Confirmation for Convertible Senior Notes due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119022393/ex99_3.htm">Form of Warrant Transactions Confirmation</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;"> for Convertible Senior Notes due
                2024</span>, filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed December 12, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.10</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000119312521113586/d158901dex102.htm">Form of Warrant Confirmation for Convertible Senior Notes due 2026</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed April 13, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.1</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000144/ex10-1.htm">Amended Non-Employee Director Compensation Policy</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the
              Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.2*</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/ix?doc=/Archives/edgar/data/0000874015/000087401522000104/form10q.htm">Registrant&#8217;s Amended and Restated Severance Benefit Plan dated March 17, 2022</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on form 10-Q for the quarter ended March 31, 2022 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.41%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</div>
        </td>

    <td style="width: 2.18%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913016208/a12-28450_1ex10d1.htm">Form of Indemnity Agreement entered into between the Registrant and its Directors and Officers with related schedule</a>, filed as an exhibit to
            the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.4</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit10_4.htm">Form of Employee Confidential Information and Inventions Agreement</a>, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year
            ended December 31, 2017 and incorporated herein by reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.5</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913081234/a13-19600_1ex10d4.htm">Registrant&#8217;s Amended and Restated 10b5-1 Trading Plan dated September 12, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.6*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465912025639/a12-1729_1def14a.htm">Registrant&#8217;s 1989 Stock Option Plan, as amended</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to Registrant&#8217;s Notice of Annual Meeting and Proxy Statement for the 2012 Annual Meeting of Stockholders, filed on April 16, 2012 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.7*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_5.htm">Form of Option Agreement under the 1989 Stock Option Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.8*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119005627/ex10_2.htm">Registrant&#8217;s Amended and Restated 2000 Employee Stock Purchase Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as
              an exhibit to Registrant&#8217;s Current Report on Form 8-K filed on March 26, 2019 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120009606/nc10007589x2_def14a.htm">Registrant&#8217;s Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan, as amended</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Notice of Annual Meeting and Proxy Statement for the 2020 Annual Meeting of Stockholders, filed on April 24, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-10.htm">10.10</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Option Agreement for Options granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option
            Plan<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.11*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top;" colspan="2">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120017841/nt10014191x2_ex99-3.htm">Form of Restricted Stock Unit Agreement for Restricted Stock Units granted under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002
              Non-Employee Directors&#8217; Stock Option Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on August 7, 2020 and incorporated
              herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.12*</div>
        </td>

    <td style="width: 2.08%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036121013999/nc10023262x1_def14a.htm">Amended and Restated Ionis Pharmaceuticals, Inc. 2011 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Notice of 2021 Annual Meeting of Stockholders and Proxy Statement filed on April 23, 2021 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-13.htm">10.13</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Option Agreement under the 2011 Equity Incentive Plan.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-14.htm">10.14</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Form of Time-Vested Restricted Stock Unit Agreement for Restricted Stock Units granted under the 2011 Equity Incentive Plan.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.15*</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-19.htm">Forms of Performance Based Restricted Stock Unit Grant Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted
              Stock Units granted prior to January 1, 2023 under the 2011 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for
            the year ended December 31, 2021 and incorporated herein by reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-16.htm">10.16</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">*</span></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Forms of Performance Based Restricted Stock Unit Grant Notice and Performance Based Restricted Stock Unit Agreement for Performance Based Restricted
            Stock Units granted beginning January 1, 2023 under the 2011 Equity Incentive Plan.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.17*</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-1.htm">Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as
              an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.18*</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-2.htm"><span style="background-color: #FFFFFF;">Form of Global Option Agreement for options granted under the Ionis Pharmaceuticals, Inc. 2020 Equity
                Incentive Plan</span></a><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.19*</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-3.htm">Form of Global Restricted Stock Unit Agreement for restricted stock units granted under the Ionis Pharmaceuticals, Inc. 2020 Equity
                Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by
              reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.20*</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036120030055/brhc10018560_ex99-4.htm">Forms of Restricted Stock Unit Grant Notice, Stock Option Grant Notice and Stock Option Exercise Notice for options granted under the Ionis
              Pharmaceuticals, Inc. 2020 Equity Incentive Plan</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">filed
              as an exhibit to the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Registrant&#8217;s Registration Statement on Form S-8 filed on December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.21</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036117028398/ex10_2.htm">Loan Agreement between Ionis Faraday, LLC and UBS AG</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated July 18, 2017,
              filed as an exhibit to the Registrant&#8217;s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.22</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036117028398/ex10_4.htm">Guaranty between the Registrant and UBS AG dated July 18, 2017</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an
              exhibit to the Registrant&#8217;s Current Report on Form 8-K filed July 21, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-23.htm">10.23</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease Agreement between the Registrant and Sudberry Development, Inc. dated October 6, 2022. Portions of this exhibit have been omitted because they
            are both (i) not material and (ii) is the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-24.htm">10.24</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase and Sale Agreement between Ionis Gazelle, LLC and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC dated as of October 20, 2022. Portions of this
            exhibit have been omitted because they are both (i) not material and (ii) is the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-25.htm">10.25</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase and Sale Agreement between the Registrant and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Oxford I Asset
              Management USA Inc. dated as of October 20, 2022. </span>Portions of this exhibit have been omitted because they are both (i) not material and (ii) is the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-26.htm">10.26</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FFFFFF; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Lease Agreement dated October 20, 2022
              between the Registrant and </span>2850 2855 &amp; 2859 Gazelle Owner (DE) LLC. Portions of this exhibit have been omitted because they are both (i) not material and (ii) is the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-27.htm">10.27</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Pledge and Security Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, Wells Fargo Bank, National Association, as
            Trustee for the Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, and U.S. Bank Trust Company, National Association. Portions of this exhibit have been
            omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-28.htm">10.28</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Assignment, Assumption and Release Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, DHC UBSCM 17 C3 Successor
            Borrower-R, LLC, Wells Fargo Bank, National Association, as Trustee for the Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, Midland Loan Services, a
            division of PNC Bank, National Association, and U.S. Bank Trust Company, National Association.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-29.htm">10.29</a></div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="2">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Defeasance Account Agreement dated as of October 20, 2022 by and among Ionis Gazelle, LLC, U.S. Bank Trust Company, National Association, U.S. Bank
            National Association, as Trustee for the Benefit of the Registered Holders of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3, and Midland Loan Services, a division of PNC Bank, National
            Association. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.30</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000056/exhibit10_80.htm">Strategic Advisory Services Agreement by and between the Registrant and Stanley T. Crooke, dated December 17, 2020</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.31</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_1.htm">Exclusive License Agreement between the Registrant and the University of Massachusetts dated January 14, 2010</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this exhibit have been omitted and separately
              filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.32</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465910026849/a10-5958_1ex10d5.htm">Research, Development and License Agreement between the Registrant and Glaxo Group Limited dated March 30, 2010</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2010 and incorporated herein by reference. Portions of this exhibit have been omitted and
              separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.33</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465911044376/a11-13864_1ex10d1.htm">Amendment #1 to the Research, Development and License Agreement dated May 11, 2011 by and between the Registrant and Glaxo Group Limited</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2011 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.34</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913016208/a12-28450_1ex10d44.htm">Amendment #2 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated October 30, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.35</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_1.htm">Amendment No. 3 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated July 10, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.36</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_2.htm">Amendment #4 to the Research, Development and License Agreement by and between the Registrant and Glaxo Group Limited dated April 10, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.37</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036114030549/ex10_3.htm">Amendment #5 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property
              Development Limited dated June 27, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2014 and
              incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.38</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_2.htm">Amendment #6 to Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property
              Development Limited dated September 2, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and
              incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.39</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401516000118/ex10_2.htm">Amendment #7 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and GlaxoSmithKline Intellectual Property
              Development Limited dated March 4, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016 and
              incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.40</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000130/ex10_2.htm">Amendment #8 to the Research, Development and License Agreement by and between the Registrant, Glaxo Group Limited and Glaxosmithkline Intellectual Property
              Development Limited, dated July 29, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and
              incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.41</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_2.htm">Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated October 26, 2011</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this
              exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.42</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401514000095/ex10_3.htm">Amendment to Amended and Restated Collaboration and License Agreement between the Registrant and Cold Spring Harbor Laboratory dated March 14, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014 and incorporated herein by reference. Portions of this
              exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.43</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465912034636/a12-6491_1ex10d1.htm">Development, Option and License Agreement between the Registrant and Biogen Idec International Holding Ltd. dated January 3, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2012 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 7.5%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.44</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="3">&#160;</td>

    <td style="width: 90.27%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036115009498/exhibit10_59.htm">Amendment #1 to the Development, Option and License Agreement between the Registrant and Biogen Idec International Holding Ltd. dated December 15, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2014 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.5%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.45</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="3">&#160;</td>

    <td style="width: 90.27%; vertical-align: top;" colspan="2">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465912054509/a12-13652_1ex10d1.htm">DMPK Research, Development, Option and License Agreement between the Registrant and Biogen Idec MA Inc. dated June 27, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2012 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.46</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913016208/a12-28450_1ex10d45.htm">Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated December 7, 2012</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2012 and incorporated herein by reference. Portions of this exhibit have been omitted and
              separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.47</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913081234/a13-19600_1ex10d2.htm">Amendment #1 to Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated August 13, 2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013 and incorporated herein by reference. Portions of this
              exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.48</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036115009498/exhibit10_61.htm">Amendment No.2 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated October 15, 2014</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2014 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.49</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401516000118/ex10_1.htm">Amendment No.3 to the Collaboration, License and Development Agreement between the Registrant and AstraZeneca AB dated January 18, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.50</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_70.htm">Amendment No. 4 to the Collaboration, License and Development Agreement by and between the Registrant and AstraZeneca AB, dated October 18, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.51</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000110465913060361/a13-13715_1ex10d1.htm">HTT Research, Development, Option and License Agreement among the Registrant, F. Hoffmann-La Roche Ltd and Hoffman-La Roche Inc. dated April 8,
              2013</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2013 and incorporated herein by reference. Portions of
              this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.52</div>
        </td>

    <td style="width: 2.23%; vertical-align: bottom; background-color: #CCEEFF;" colspan="3">&#160;</td>

    <td style="width: 90.13%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000057/ex10_2.htm">Amendment #1 to HTT Research, Development, Option and License Agreement between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc. dated
              January 9, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference.
              Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.53</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top;" colspan="3">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000057/ex10_1.htm">Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc. dated January 8, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.54</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;" colspan="3">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_3.htm">Amendment Number One to the Second Amended and Restated Strategic Collaboration and License Agreement between the Registrant and Alnylam Pharmaceuticals, Inc.
              dated July 13, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by
              reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.55</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top;" colspan="3">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401515000082/ex10_1.htm">Strategic Collaboration Agreement between the Registrant and AstraZeneca AB dated July 31, 2015</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with
              the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.56</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;" colspan="3">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_69.htm">Amendment No. 1 to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB, dated October 18, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by reference. Portions of this exhibit
              have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.57</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top;" colspan="3">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401520000115/ex10_2.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 2 dated April 30, </span>2020<span style="text-decoration: underline;"> to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not
              material and (ii) is the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.58</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000056/exhibit10_79.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 3 dated December 17, </span>2020<span style="text-decoration: underline;"> to the Strategic Collaboration Agreement by and between the Registrant and AstraZeneca AB dated July 31, 2015</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both
              (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.59</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/1662524/000104746917001995/a2231300zex-10_7.htm">Strategic Collaboration, Option and License Agreement by and among Akcea Therapeutics, Inc. and Novartis Pharma AG, dated January 5, 2017</a>,
            filed as an exhibit to Akcea Therapeutics, Inc.&#8217;s Form S-1 filed March 27, 2017 and incorporated herein by reference.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.60</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/1662524/000156459019018117/akca-ex101_176.htm">Amendment No. 1 to the Strategic Collaboration, Option and License Agreement between Akcea Therapeutics, Inc. and Novartis Pharma AG dated February
              22, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to Akcea Therapeutics, Inc.&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 30, 2019 and incorporated herein by
              reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.61</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401517000033/ex10_2.htm">Stock Purchase Agreement among the Registrant, Akcea Therapeutics, Inc. and Novartis Pharma AG</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated January 5, 2017, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2017 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.62</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000047/exhibit10_17.htm">Research Collaboration, Option and License Agreement between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> dated December 19, 2017, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2017 and incorporated herein by reference. Portions of this exhibit have been omitted and
              separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.63</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000060/ex10_2.htm">Development, Commercialization, Collaboration, and License Agreement by and between the Registrant and Akcea Therapeutics, Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated March 14, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.64</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000060/ex10_3.htm">Amended and Restated Services Agreement by and between the Registrant and Akcea Therapeutics, Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated March 14, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended March 31, 2018 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.64%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.65</div>
        </td>

    <td style="width: 1.94%; vertical-align: bottom; background-color: #FFFFFF;" colspan="2">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000105/ex10_1.htm">New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated April 19, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein by reference.
              Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.66</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000130/ex10_1.htm">Amendment No. 1 to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement between the Registrant and Biogen MA
              Inc., dated August 16, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 and incorporated
              herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.67</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000056/exhibit10_81.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Side Letter dated December 31, </span>2020<span style="text-decoration: underline;"> to the New Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc. dated April 19,
                  2018</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2020 and incorporated herein by
              reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.68</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401518000105/ex10_2.htm">Stock Purchase Agreement by and between the Registrant and Biogen MA Inc.</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">,
              dated April 19, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and incorporated herein by reference.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.69</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_67.htm">Factor B Development Collaboration, Option and License Agreement by and between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc.,
              dated October 9, 2018,</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and incorporated herein by
              reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.70</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000148/ex10-1.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">First Amendment dated July 8, </span>2022<span style="text-decoration: underline;"> to Factor B Development, Collaboration, Option and License Agreement by and between the Registrant, F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc.</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, dated October 9, 2018, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022. Portions of this exhibit have been
              omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.71</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401519000045/exhibit10_68.htm">Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant
              and Biogen MA Inc., dated October 17, 2018</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2018 and
              incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.72</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036117009823/exhibit10_61.htm">Letter Agreement between the Registrant and Biogen MA Inc. dated October 28, 2016</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2016 and incorporated herein by reference. Portions of this exhibit have been omitted and separately filed with the SEC with a
              request for confidential treatment.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.73</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000114036119014492/ex10_1.htm">Amendment No. 1 to Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between
              the Registrant and Biogen MA Inc., dated May 2, 2019</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019
              and incorporated herein by reference.</span></div>
        </td>

  </tr>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">80</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.74</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401520000115/ex10_1.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Side Letter dated June 11, </span>2020<span style="text-decoration: underline;"> to the Second Amended and Restated Strategic Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc.
                  dated October 17, 2018</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and incorporated
              herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.75</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000166/ex10-2.htm">Collaboration and License Agreement by and between the Registrant and BicycleTX Limited dated July 9, 2021</a>, filed as an exhibit to the Registrant&#8217;s
            Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and incorporated herein by reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the type that the Registrant treats as private or confidential</span>.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.76</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-83.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 1 dated December 17, </span>2021<span style="text-decoration: underline;"> to the Collaboration and License Agreement by and between the Registrant and BicycleTX Limited dated July 9, 2021</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.77</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000168/ex10-1.htm"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Amendment No. 2 dated July 28, </span>2022<span style="text-decoration: underline;"> to the Collaboration and License Agreement by and between the Registrant and BicycleTx Limited dated July 9, 2021</span></span></a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.78</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401521000166/ex10-1.htm">Amended and Restated Neurology Drug Discovery and Development Collaboration, Option and License Agreement by and between the Registrant and Biogen MA Inc.
              dated July 12, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as an exhibit to the Registrant&#8217;s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and incorporated herein by
              reference. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.79</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="https://www.sec.gov/Archives/edgar/data/874015/000087401522000079/exhibit10-84.htm">Collaboration and License Agreement by and between Akcea Therapeutics, Inc. and AstraZeneca AB dated December 6, 2021</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, filed as </span>an exhibit to the Registrant&#8217;s Annual Report on Form 10-K for the year ended December 31, 2021 and incorporated herein by reference<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.&#160; Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</span></div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-80.htm">10.80</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
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            because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit10-81.htm">10.81</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty Purchase Agreement by and between the Registrant, Akcea Therapeutics, Inc. and Royalty Pharma Investments 2019 ICAV dated as of January 9,
            2023. Portions of this exhibit have been omitted because they are both (i) not material and (ii) the type that the Registrant treats as private or confidential.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit14.htm">14</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Code of Ethics.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit21-1.htm">21.1</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">List of Subsidiaries for the Registrant.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit23-1.htm">23.1</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Consent of Independent Registered Public Accounting Firm.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.1</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Power of Attorney &#8211; Included on the signature page of this Annual Report on Form 10-K.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit31-1.htm">31.1</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Executive Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit31-2.htm">31.2</a></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification by Chief Financial Officer Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="exhibit32-1.htm">32.1</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">+</span></div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Certification Pursuant to 18 U.S.C. Section 1350 as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">101</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #FFFFFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial statements from the Ionis Pharmaceuticals, Inc. Annual Report on Form 10-K for the year ended December 31, 2022, formatted in Extensive Business Reporting Language (XBRL): (i) consolidated balance sheets, (ii) consolidated statements of operations,
            (iii) consolidated statements of comprehensive income (loss), (iv) consolidated statements of stockholders&#8217; equity (v) consolidated statements of cash flows, and (vi) notes to consolidated financial statements (detail tagged).</div>
        </td>

  </tr>

  <tr>

    <td style="width: 7.78%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div>
        </td>

    <td style="width: 1.81%; vertical-align: bottom; background-color: #CCEEFF;">&#160;</td>

    <td style="width: 90.42%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cover Page Interactive Data File (formatted in iXBRL and included in exhibit 101).</div>
        </td>

  </tr>


</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">*</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Indicates management compensatory plans and arrangements as required to be filed as exhibits to this Report pursuant to Item 14(c).</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">+</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that
            section, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 133, as amended, or the Securities Exchange Act of 1934, as amended.</div>
        </td>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">81</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Signatures"><!--Anchor--></a>SIGNATURES</div>

  <div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this report on
    Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized on the 22<sup>nd</sup> day of February, 2023.</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

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    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 50.19%; vertical-align: top;" colspan="2">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">IONIS PHARMACEUTICALS, INC.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">By:</div>
        </td>

    <td style="width: 45.56%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

  </tr>

  <tr>

    <td style="width: 49.81%; vertical-align: top;">&#160;</td>

    <td style="width: 4.63%; vertical-align: top;">&#160;</td>

    <td style="width: 45.56%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Chief Executive Officer (Principal executive officer)</div>
        </td>

  </tr>


</table>
  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">POWER OF ATTORNEY</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Brett P. Monia and Elizabeth L.
    Hougen, or any of them, his or her attorney-in-fact, each with the power of substitution, for him or her in any and all capacities, to sign any amendments to this Report, and to file the same, with exhibits thereto and other documents in connection
    therewith, with the Securities and Exchange Commission, hereby ratifying and confirming all that each of said attorneys-in-fact, or his or her substitute or substitutes, may do or cause to be done by virtue hereof.</div>

  <div><br />
  </div>

  <div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf
    of the Registrant and in the capacities and on the dates indicated.</div>

  <div style="text-align: left;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

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    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Signatures</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Title</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Date</div>
        </td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">&#160;</td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ BRETT P. MONIA</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director and Chief Executive Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
        </td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Brett P. Monia, Ph.D.</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(Principal executive officer)</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top;">&#160;</td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">&#160;</td>

  </tr>

  <tr>

    <td style="width: 30.39%; vertical-align: top; border-bottom: #000000 2px solid;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ELIZABETH L. HOUGEN</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Executive Vice President, Finance and Chief Financial Officer</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Elizabeth L. Hougen</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
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        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH LOSCALZO</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
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        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph Loscalzo, M.D., Ph.D.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ SPENCER R. BERTHELSEN</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
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        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Spencer R. Berthelsen, M.D.</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ALLENE M. DIAZ</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Allene M. Diaz</div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ MICHAEL HAYDEN</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

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    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Michael Hayden, CM OBC MB ChB PhD FRCP(C) FRSC</div>
          <div>&#160;</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOAN E. HERMAN</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joan E. Herman</div>
        </td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH KLEIN</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph Klein, III</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ B. LYNNE PARSHALL</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Director and Senior Strategic Advisor</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">B. Lynne Parshall, J.D.</div>
        </td>

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    <td style="width: 49.28%; vertical-align: top;">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ JOSEPH H. WENDER</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

    <td style="width: 49.28%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lead Independent Director</div>
        </td>

    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

    <td style="width: 16.06%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>
        </td>

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    <td style="width: 30.39%; vertical-align: top;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Joseph H. Wender</div>
        </td>

    <td style="width: 2.05%; vertical-align: top;">&#160;</td>

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    <td style="width: 2.22%; vertical-align: top;">&#160;</td>

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    <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">82</div>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">IONIS PHARMACEUTICALS, INC.</div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">INDEX TO CONSOLIDATED FINANCIAL STATEMENTS</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Page</div>
        </td>

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    <td style="width: 93.34%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#AuditReport">Report of Independent Registered Public Accounting Firm</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> (PCAOB ID <span style="-sec-ix-hidden:Fact_0a51eb84ed824aa593647b4f154e171c">42</span>)</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-2</div>
        </td>

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    <td style="width: 93.34%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#BalanceSheet">Consolidated Balance Sheets</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> at December 31, 2022 and 2021</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-4</div>
        </td>

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    <td style="width: 93.34%; vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#IncomeStatement">Consolidated Statements of Operations</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2022, 2021 and 2020</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-5</div>
        </td>

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    <td style="width: 93.34%; vertical-align: top; background-color: #FFFFFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#ComprehensiveIncome">Consolidated Statements of Comprehensive Loss</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2022, 2021 and 2020</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-6</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Equity">Consolidated Statements of Stockholders&#8217; Equity</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2022, 2021 and 2020</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-7</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#CashFlows">Consolidated Statements of Cash Flows</a><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for the years ended December 31, 2022, 2021 and 2020</span></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #FFFFFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-8</div>
        </td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><a style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;" href="#Notes">Notes to Consolidated Financial Statements</a></div>
        </td>

    <td style="width: 6.66%; vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">F-10</div>
        </td>

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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="AuditReport"><!--Anchor--></a>REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div>

  <div style="text-align: center;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To the Stockholders and Board of Directors of Ionis Pharmaceuticals, Inc.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Opinion on the Financial Statements</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have audited the accompanying consolidated balance sheets of Ionis Pharmaceuticals, Inc. (the Company) as of December 31, 2022 and 2021, the related
    consolidated statements of operations, comprehensive loss, stockholders&#8217; equity and cash flows for each of the three years in the period ended December 31, 2022, and the related notes (collectively referred to as the &#8220;consolidated financial
    statements&#8221;). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the Company at December 31, 2022 and 2021, and the results of its operations and its cash flows for each of the
    three years in the period ended December 31, 2022, in conformity with U.S. generally accepted accounting principles.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company&#8217;s internal
    control over financial reporting as of December 31, 2022, based on criteria established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated
    February 22, 2023 expressed an unqualified opinion thereon.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis for Opinion</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">These financial statements are the responsibility of the Company&#8217;s management. Our responsibility is to express an opinion on the Company&#8217;s financial
    statements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the
    Securities and Exchange Commission and the PCAOB.</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
    assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error
    or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting
    principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Critical Audit Matter</div>

  <div><br />
  </div>

  <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was communicated or required
    to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical
    audit matter does not alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the
    accounts or disclosures to which it relates.</div>

  <div><br />
  </div>

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  <tr>

    <td style="width: 15.42%; vertical-align: top;">&#160;</td>

    <td style="width: 2.85%; vertical-align: top;">&#160;</td>

    <td style="width: 81.74%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Estimated Liability for Clinical Development Costs</div>
          <div>&#160;</div>
        </td>

  </tr>

  <tr>

    <td style="width: 15.42%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Description of the Matter</div>
        </td>

    <td style="width: 2.85%; vertical-align: top;">&#160;</td>

    <td style="width: 81.74%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, the Company accrued $116.5 million for accrued clinical development costs. As discussed in Note 1 to the consolidated
            financial statements, the Company estimates their liability for clinical development costs incurred and services received but not yet billed for, and maintains an accrual to cover these costs. These costs primarily relate to third-party
            clinical management costs, laboratory and analysis costs, and investigator grants. The Company estimates their liability using assumptions about study and patient activities and the related expected expenses for those activities determined
            based on the contracted fees with service providers.</div>
          <div>&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Auditing the Company&#8217;s accruals for clinical development costs is especially complex as the information necessary to estimate the accruals is
            accumulated from multiple sources. In addition, in certain circumstances, the determination of the nature and level of services that have been received during the reporting period requires judgment because the timing and pattern of vendor
            invoicing does not correspond to the level of services provided and there may be delays in invoicing from vendors.</div>
        </td>

  </tr>


</table>
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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">84</div>

    </div>

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  </div>

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  <tr>

    <td style="width: 15.42%; vertical-align: top;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">How We Addressed the Matter in Our Audit</div>
        </td>

    <td style="width: 2.85%; vertical-align: top;">&#160;</td>

    <td style="width: 81.73%; vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We obtained an understanding and evaluated the design and tested the operating effectiveness of controls over the accounting for accrued clinical
            development costs. This included controls over management&#8217;s assessment of the assumptions and accuracy of data underlying the accrued clinical development costs estimate.</div>
          <div>&#160;</div>
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">To test the accuracy of the Company&#8217;s accrued clinical development costs, we performed audit procedures that included, among other procedures,
            obtaining supporting evidence of the research and development activities performed for significant clinical trials. We corroborated the status of significant clinical development costs through meetings with accounting and clinical project
            managers. We compared the costs for a sample of transactions against the related invoices and contracts, and examined a sample of subsequent payments to evaluate the accuracy of the accrued clinical development costs and compared the results to
            the current year accrual.</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ <ix:nonNumeric name="dei:AuditorName" id="Fact_e5f9ed5d79794d53b4839a4ac1983fb1" contextRef="c20220101to20221231">Ernst &amp; Young LLP</ix:nonNumeric></div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have served as the Company&#8217;s auditor since 1989.</div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="dei:AuditorLocation" id="Fact_b850c2063e1048d981fa70bd3d2c8c24" contextRef="c20220101to20221231">San Diego, California</ix:nonNumeric></div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div>

  <div><br />
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  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="BalanceSheet"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED BALANCE SHEETS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands, except share data)</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: center; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">ASSETS</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current assets:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash and cash equivalents</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Short-term investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Property, plant and equipment, net</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current liabilities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounts payable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_d2f4209896534c34b236247e2f014047" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,921</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccountsPayableCurrent" id="Fact_4a77a0a95bc24ec9879730f3c54c5767" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,904</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_6757e467d4ca4989a92e1b0146882726" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,178</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EmployeeRelatedLiabilitiesCurrent" id="Fact_e13f67f862ed4bf9b0ccd8241eabef36" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">38,810</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_70b781ca48864bb9b31bb2272f1c75fd" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,101</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_969294300c9b472f89e106ba0b60bd69" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">88,560</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes payable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_0ac97222f6364543b31753077f08b8f9" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,249</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedIncomeTaxesCurrent" id="Fact_924182cca560478288901c6e2b93dbec" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">36</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current portion of deferred contract revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_1671964ce90d42048bf1ccad365328ff" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">90,577</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityCurrent" id="Fact_8cde4fe9123d48c398e9f1ba6812728d" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">97,714</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilitiesCurrent" id="Fact_527c9c2c1fd8482a8db2ee3873cb6481" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,535</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilitiesCurrent" id="Fact_a0238d8cc02543e9b5dae4ea5a8e530b" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,526</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            convertible senior notes, net</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiabilityNoncurrent" id="Fact_8ff8e3dd4c0843b3b44c6f4288a8d906" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,941</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term mortgage debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -36pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term obligations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilitiesNoncurrent" id="Fact_71c2251f096f468a93259e2645561c05" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,946</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Liabilities" id="Fact_e80cd271efab4a4c8c3d5beb70de894b" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,839,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stockholders&#8217; equity:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            par value; <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_9a0912d45871495e9d5ffb48117b86ac" contextRef="c20211231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_7cf23bc0b3da4da3818fa69653f089c6" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">300,000,000</ix:nonFraction></ix:nonFraction></span> shares authorized, <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_6b03136461bc406ab4ea599c454895bc" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_83959e73ecef45b7bf3b111575f95c72" contextRef="c20221231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">142,057,736</ix:nonFraction></ix:nonFraction></span> and <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_ae85ba7613de4a38acdf354791b136fa" contextRef="c20211231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_2e7ea39c8d104a0ca5cf2a5f9cdbc016" contextRef="c20211231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">141,210,015</ix:nonFraction></ix:nonFraction></span> shares issued and outstanding at December 31,
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CommonStockValue" id="Fact_942a957fd1a642b4a9846b941b383984" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">141</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additional paid-in capital</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdditionalPaidInCapitalCommonStock" id="Fact_3f85039492a3477ba262bbaf1e3a9940" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,059,850</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="IncomeStatement"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF OPERATIONS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands, except for per share amounts)</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_fdaf4e7de3e14bc88036b45f358b0bc2" contextRef="c20220101to20221231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">242,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7043d15f95394ffe96f0662fa9fad2fa" contextRef="c20210101to20211231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">267,776</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ac6e240eca5848d5badb78f0ca60c1a3" contextRef="c20200101to20201231_ProductOrServiceAxis_SpinrazaRoyaltiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">286,583</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">TEGSEDI and WAYLIVRA revenue, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e82af709616c487887988783c2c8d9c7" contextRef="c20220101to20221231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,051</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a83fa126a57b41d599f30e7cad218b6c" contextRef="c20210101to20211231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,500</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ad9a698af9f24b05865de462af852631" contextRef="c20200101to20201231_ProductOrServiceAxis_ProductMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">69,999</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 8.85pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Licensing and other royalty revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research and development revenue:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: 9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Eplontersen joint development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5c8de2bd919f4591baa9a3fd8807bffa" contextRef="c20220101to20221231_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">76,787</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6cc8f959f1a84a3882c5922b1c402e36" contextRef="c20210101to20211231_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_5fa9a425ee1840dfbd98ea8bde289a33" contextRef="c20200101to20201231_ProductOrServiceAxis_EplontersenJointDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: 18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total research and development revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_98715a1d07f649c3838b9f140c95b5ed" contextRef="c20220101to20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">284,009</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_2cf6fc29b4ae47358cac42657a6e869e" contextRef="c20210101to20211231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">468,061</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7efcdc0bff8d4b0388346f3e3a31b8c0" contextRef="c20200101to20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">364,565</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_00980b8be4a74f4fbdcc3edafc17198f" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">587,367</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_538efe69e72243699e94c3aa305b19c1" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">810,456</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_32e9022328524875ac203ea1d35a74e1" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">729,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expenses:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss from operations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other income (expense):</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets1" id="Fact_db456fea13e442f58dc87cedc52ba432" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_516792b864244fea81a047aaeb6a86f7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">7,274</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_df31a318f46e40c0bad155f92c7bffb9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">9,760</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherNonoperatingIncomeExpense" id="Fact_95a44b06b165497c90c92f0ecb837d5d" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">62</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss before income tax benefit (expense)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_786ffe6ab1c44b428a4fc9133fa1fb21" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">257,985</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_d3bdd0f2404d4109ab52a26b4122517d" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">29,148</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_abea68078429482298990eda2a273682" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">134,552</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income tax benefit (expense)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_25eb94c1a44848a4ae8038f050bdb154" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_5b1c8e20abb84c34b626e66d15f639fe" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">551</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_4e00bc85f9de44bc9fae3e310059dd54" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">345,191</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_eed2832b2f23443a8a7b6a11b3b5c8be" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAttributableToNoncontrollingInterest" id="Fact_2924ba1e6c0449e68559e8bfbf1fff33" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">35,480</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_d67d140ccc41433e809a30cd81e184e2" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_41f8afe988ab4add8c88a8e7caefd925" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_bb9a33cf051a47359fe47c04a4566435" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">444,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_f5d991f3a037439da834811b6b2c9680" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_ad4c690aa177438c98b7e63bbcd61da7" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.90</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_7cdec1311ca947dfbacb3efc23b5ef61" contextRef="c20210101to20211231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_2c847af7934d4aee8d1e75c8c45eaaed" contextRef="c20210101to20211231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.20</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_f8c8aa80739c448c87fb108a521d3b50" contextRef="c20200101to20201231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_dc69ad9fdaac456cb95135c896add9e4" contextRef="c20200101to20201231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">3.18</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares used in computing basic and diluted net loss per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_240816d0c41d4bb8946ce32d9ec238f1" contextRef="c20220101to20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_974483869c87424686f8a9d8ad9407f8" contextRef="c20220101to20221231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,848</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding" id="Fact_9344acea647e4a1f9b5346ba564f05a7" contextRef="c20210101to20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_57a007ce704b4b8e9d16bf5187758b1a" contextRef="c20210101to20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,021</ix:nonFraction></ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="ComprehensiveIncome"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax" id="Fact_33ff3ee28c9b4c45b1a904711a9fffdb" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_0118d01a0fc0483d942b9e51407b4717" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">417</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_e0cf23c629544136a3b19d99634a49a6" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">111</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_107faab7668f4901940b3c076c0c0ec6" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">617</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" id="Fact_841879a515ca4d0d9d8d3706c43e9260" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" id="Fact_ced0ce9e26744592ad27d150c4780638" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" id="Fact_8dde645333454befac18a987f4b4ffbb" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">127</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_88990aa910f44465b514db16de1b6797" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">294,534</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_a94a014398884db3aad264a9afa0f0b9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">40,194</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest" id="Fact_952a61bbba0241e4b821f51c3f0cbaf0" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">475,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_0a2ffbf7523a40bfb67425a2f824fdda" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_835fc2d29a554273b86faf6556c423be" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest" id="Fact_7354d55541b84356989b29706bcadb0e" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">35,480</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Comprehensive loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_c084b014906646ef8b8e0d1564259a56" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">294,534</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ComprehensiveIncomeNetOfTax" id="Fact_a5f2d997e0854eb2bac6beedf43dbdc0" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">40,194</ix:nonFraction></div>
        </td>

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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Equity"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">CONSOLIDATED STATEMENTS OF STOCKHOLDERS</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> EQUITY</span></div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Additional</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Ionis</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Interest in Akcea</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Stockholders</span>&#8217;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Description</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Paid in Capital</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Comprehensive Loss</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deficit</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Therapeutics, Inc.</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Equity</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2019</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_e117c0623dcf44afaffde41830ff31f2" contextRef="c20191231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,340</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_c2ee42f06fe64835a05ef7841d2d5bee" contextRef="c20191231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">140</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_61b12d938cc04bbd933859666c726023" contextRef="c20191231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,985,650</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_761affc8eaf842578c2a954083f3e28b" contextRef="c20191231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">25,290</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_7ce172fc43e84fe9a84cda9a4771f340" contextRef="c20191231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">596,495</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d7625d3c6da54d3c8303ca9e6db6c22e" contextRef="c20191231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,364,005</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e263af9230d74dc0984e6063677dc5d2" contextRef="c20191231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">213,454</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_8a8a123d035043aebb0000237fdd6e28" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,577,459</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_b699b94c66764330a7a4dd60cfe07928" contextRef="c20200101to20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_031beff8601a4b50b1c41faf88b4db91" contextRef="c20200101to20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c8cd11420aa41ba8dbf194cc8c306a6" contextRef="c20200101to20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_50a37a75aedf40108038ac8776d5bc2a" contextRef="c20200101to20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_569648b85807448bbb2acc6eb5277fac" contextRef="c20200101to20201231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_d53119298ae5494a8a29986a67a7b5ac" contextRef="c20200101to20201231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Noncontrolling interest in Akcea Therapeutics, Inc.</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_e78d038faf194359a7ce32e2ba8548cc" contextRef="c20200101to20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_8a7b1d7fe0d044b6a8aae81146c4447b" contextRef="c20200101to20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">42,563</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_6e30f990ab16415483b4a2a3e927bf8a" contextRef="c20200101to20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">428</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_297591177a834d7c9bfdced2ced813e0" contextRef="c20200101to20201231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:MinorityInterestPeriodIncreaseDecrease" id="Fact_2424cb31a8f84a03b3c029dab7550d0f" contextRef="c20200101to20201231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">42,991</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2020</span></div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_60e0ac539c624466a7e961a5cda44d3a" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,366</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_4b39284014b0418f90e000374da7580f" contextRef="c20201231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">140</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6585fe6638524b79b937ab63b9db5d75" contextRef="c20201231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,895,519</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d286f9a454bc438c8afed1012262b3ab" contextRef="c20201231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">21,071</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_2ff016c0f0f747c19ebd4bac48864260" contextRef="c20201231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,131,306</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_5fa68cfcb9f54851a4ae9660cdc60d85" contextRef="c20201231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">743,282</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_7adb69797e0542af967701b5578982ac" contextRef="c20201231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_61512a893ff14270a3f4c0015b93fa30" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">743,282</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_48bf356e63ad4d97b55fa3ddcc9213c8" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_e8dd2525dbd042a1bcdc939a738cde79" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_9afeaa7611344fda84c4bfc3dcdc8188" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_338f9e0b9ece40f2b5a46dd2eb3bc945" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_1726fa2840cb4086b6f7cf5c3e66cd1f" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_5f64a422578244348f047cc3f91c1184" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_755544668a704c22979858000bfde38a" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_5b6feeff0a314136a4fe63dbb89869e6" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_f70df17298104bb29ef7861c6b585f0e" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_fdb4ab077b324877bfe3b9a67020fb1a" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,486</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_6fb19bacbb7d415481e528316894c7ee" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_50d79b4af6c14ee1864560317e9c1c75" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,486</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_c7e7bcabb0e04e1fb029f80374e07891" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_333a9818653b4dfaab93cbf0c5a77aaa" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" id="Fact_80b4bbd8324546a3a831e14d4d01d952" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of common stock in connection with employee stock plans</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensation" id="Fact_3e593fdd22684db1bfb738748b3da710" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,132</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_e0f954339b0b486b8eb0622218c8430b" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_f1f39c8f1962432e8fd6b5b78bfe0cf1" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_ab997a8b7d4a4042ab48b4f20127f6b2" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,564</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_cad50941c137465ebaf6b4cbae4f7296" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_5651bfc11ac84711aed5e4ab4d579d5a" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,564</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Issuance of warrants</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_b282b1c69ac2407bac89b1764a7fd341" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_aa9faaf193e44b488fa79070c6199be0" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">89,752</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_8e4734be5ffc4dc0a86cf6aa983a24db" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_a9c122da530d40339568a92f44a2951d" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_8b96eee772e849ef83bc12e94b6a273b" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">89,752</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_f289054498844198abe3109e834c766e" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalWarrantIssued" id="Fact_f82bd066cd754e69bc27aa7297af5db2" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">89,752</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchase of note hedges</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_8c5fc0160a694b448e6d8f83d05f6f17" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_3a6559d9b3714ed5b2bef965c79e912d" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_962069d8e369472e8385544ba87165c1" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">136,620</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_fbe88d15ab7c45be964bf1d812a2f938" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalOther" id="Fact_4d04c97e8cc14cf7b8848f5427c598a9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">136,620</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_4769b7f8ea594366a73ab91db2a60fa9" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_29f9f2041bff44918a0cfddfa16cbc02" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,678</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3719dc6e9f1b486dae7106b08772f201" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_49a44ab58d2d49f8b1053aca4e966011" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_dc61a61ec6984fbb83f9646ef7ebb30f" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,678</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_1bfc73073b1042a18e0eb1fb3c034797" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_c9e019303e9b4ff1b01e682eefe65def" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,678</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_4ae64fbea2b243829db015f863e1a525" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">288</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_bb0a6cb28ba64220b97554fd600a837f" contextRef="c20210101to20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_b049e26291e240409287825db6851635" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,725</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_69a5b77d2ba2483884724f7deb4c0ae6" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_cbfd3f29efe544d8b18e1d3d119b4122" contextRef="c20210101to20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_06512793fca04aafad083ac0b4088b51" contextRef="c20210101to20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,725</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_fecfcab42153456ebe04678e0c6b6508" contextRef="c20210101to20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_6e495bacb01a4d498554da8a760530b3" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,725</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2021</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_dcb079e20cba446096baf2d275d36dd5" contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,210</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d01227787819409c840436d67e7d48a3" contextRef="c20211231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">141</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_acc570beab1c44b1b82a54a05d599805" contextRef="c20211231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,964,167</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_23b29f4e087c4f1ca664c32300610294" contextRef="c20211231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,668</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_71c821501e124dbfa12ced3159be86a4" contextRef="c20211231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,159,903</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_b1711f8987654d248ea55f4d0db1c024" contextRef="c20211231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">771,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_2efb06adbdd5486db43852bff651ab65" contextRef="c20211231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_e7271e8b196b47b3bbe7e15968a86b6b" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">771,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_833dc2d79f584f5cadd8fbb8afa29236" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_688bec339ca64d21a9b56fd99f2a667e" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_2c0f61fe913a4e9c87a2ecd4f94a7897" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_3178904620f649fd815c50c1e7ed399f" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_f243d5703018413db94848f32ca2937c" contextRef="c20220101to20221231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_1594a599ee844816944f74aef5e5ce6b" contextRef="c20220101to20221231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_a25515ec6f7446728b15a5adbf23f4bf" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Change in unrealized losses, net of tax</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_1d4ee35e2c024559a37a84c8318f1601" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_7d3cc28a8d714c2892f946fd7d69085f" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_5b13464fcc914218a22621cadb3f01cf" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_9612b70e89ab4a65902c6735833f3cf2" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_2efba56ab30f4a1787e7e7083c0cea31" contextRef="c20220101to20221231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_30984b5d00c64ee78163e3107fdca05d" contextRef="c20220101to20221231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent" id="Fact_48167af9646f4982bdfaad59e0abcc5e" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign currency translation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_6a5d7bca0e5f47b58411c7c493d6112c" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockIssuedDuringPeriodValueShareBasedCompensationGross" id="Fact_95783d31dfff4e85b4c5c96c65e53165" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3984b222032b4f89a6067a1a1115ba11" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_aee075691688409a968dbc6bfaabb0b8" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_56cd8c22ed5544bbb6a31360f46ba604" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_3058a5ae36ca41e8bec4bc5d2b8cd05a" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_a248bf7583bf4355a4573ce2eac838af" contextRef="c20220101to20221231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue" id="Fact_1d5e95fbc00e4e7180ca1c989b620568" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:SharesPaidForTaxWithholdingForShareBasedCompensation" id="Fact_bb9a0a3c8c0f460d8907df35ba024998" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">346</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_89851b9aadd54cb785b1306c44008fb2" contextRef="c20220101to20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_1c7c759f6400434fbbc88dcf198244d3" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_e3a3359a6199474d974e8f7baa127a45" contextRef="c20220101to20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_2980774b43c54434b88a59ac547cddbb" contextRef="c20220101to20221231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_d14b5866235c4ab1aeb47f1c1c6ca402" contextRef="c20220101to20221231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_0c79c70d50d2443aa074c4fd2102d981" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 20%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Balance at December 31, <span style="text-indent: 0pt;">2022</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharesIssued" id="Fact_1d1f0719541143f2ae5ac80a19fb4007" contextRef="c20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">142,058</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_74064f8288c1486bb2496106d6fd8aa7" contextRef="c20221231_StatementEquityComponentsAxis_CommonStockMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">142</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_41e9cc98d38a41778cf6eb70280117c2" contextRef="c20221231_StatementEquityComponentsAxis_AdditionalPaidInCapitalMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,059,850</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_aced03aa44534069aacaa219a523b4fc" contextRef="c20221231_StatementEquityComponentsAxis_AccumulatedOtherComprehensiveIncomeMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">57,480</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_05be694dedb54ba2866c147ae24a252c" contextRef="c20221231_StatementEquityComponentsAxis_RetainedEarningsMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,429,625</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_08847d93eb194cbc8441f04f28fab350" contextRef="c20221231_StatementEquityComponentsAxis_ParentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">572,887</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_357e33071adb4d44a4c223b12a238d2f" contextRef="c20221231_StatementEquityComponentsAxis_NoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 7%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_73202c7946b84e00a0ec046191213ebc" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">572,887</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">89</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="CashFlows"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSOLIDATED STATEMENTS OF CASH FLOWS</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(In thousands)</div>

  <div><br />
  </div>

  <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_74418700e541478eadc5aced379a124b" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">269,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_3fb9b4a0ea3c4f27a1399c4165b5801f" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">28,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_187fd18217c9402ba4a18dc3da990453" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,362</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_97e6d2268c574e3d8f29df4998aec6d6" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,721</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAssetAmortizationExpense" id="Fact_215c70afe4f549f890056ebd2c3be83f" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,731</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_c4419687fb464fe5bdc6e0d2984bef36" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,415</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_2510d199eca04ba290db4822e474a069" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,352</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfIntangibleAssets" id="Fact_dfcf2be324b646d9bb90e538cfcfa5d7" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,064</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of premium on investments, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_19b1a8aca8b7454d8d920b65112f9717" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">7,389</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_1d483a94eb99484aaf16db7faa11b937" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">17,776</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccretionAmortizationOfDiscountsAndPremiumsInvestments" id="Fact_a3256c7afeb0459b896a0c3caee0e2f8" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,521</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amortization of debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_b85286437b974418ba977d6f06debc76" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,373</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_a644e66590634fa5857536f88b90ec7a" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,958</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_8299ca7b84184a219ca22bdd8885ded6" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,255</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation expense</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_de86964f1c204681a24953a828812433" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_b7ce371b025e4c42b0adacb5ab3929a4" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,678</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensation" id="Fact_1639ac5ab8ad4f01b5b69c5287ccb579" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">230,117</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss on early retirement of debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_e867493ef4ff4d3ebe904b6d5afd0509" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_746295e1c66f4d83896cdde464856584" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">8,627</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_92b9752085fc414faf69a3c81e0bfb45" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-cash losses related to disposal of property, plant and equipment</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:GainLossOnDispositionOfAssets" id="Fact_08118b7aff0443108358f18bd4c22ad3" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">531</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxesAndTaxCredits" id="Fact_5c2bc7d8b78d4b099c1e6ade218bd61f" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Changes in operating assets and liabilities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Contracts receivable</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerAsset" id="Fact_f68a004f44a6458192f1daa14c3a54bb" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">36,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Inventories</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_085c28a5897b4fdc902bd3eb96b38cfe" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">2,773</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInInventories" id="Fact_721b959345b1466b92ba324d3da7222a" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,841</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other current and long-term assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:IncreaseDecreaseInIncomeTaxesReceivablePayable" id="Fact_39986573e52c4b22a4e7523064d4a2b9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,008</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInAccountsPayable" id="Fact_a2882fd1ebf24bd894bdd232be12bb88" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,094</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable" id="Fact_cbe5d4f72a7b47b6bbf20a734efa0ff9" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,213</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable" id="Fact_928bf4ded5484066ada8046ae256e5bd" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,288</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_be8c0f046cfa423dbf8943de92eacba3" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,368</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_c2e1e6792bbf4d45bb9581a0838da942" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">26,918</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherEmployeeRelatedLiabilities" id="Fact_1610f4d30b0d484693cb2ccb1dd531cd" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,371</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accrued liabilities and other current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" id="Fact_c2d76681eaf6401eb0820fac87914240" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">46,695</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" id="Fact_46fb0027cc774970b1e33fe73a8d0134" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">8,381</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" id="Fact_fd2ee65b38e940ef8147608e66310a1d" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred contract revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_6eed7a6f16674d629d60401fee845c19" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">71,248</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_860c87bb13ca432ab6413fcb41ab7d48" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">82,829</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncreaseDecreaseInContractWithCustomerLiability" id="Fact_9c03c531ef514d558aa7fca25bb6b718" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">75,910</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by (used in) operating activities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_19c256c737ca49a4a82b43e1d4907fd7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">274,370</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_6ac8228472434c89928ff5906d8cdfa8" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">30,799</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInOperatingActivities" id="Fact_39199cc3649f4be29630e4d9f60a5e3f" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,892</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Investing activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of short-term investments</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of property, plant and equipment</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_af7f2fbf99644b83883250b2765bc5ae" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,721</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquirePropertyPlantAndEquipment" id="Fact_28d3f3d53dd04a84a5b65fcacb820e59" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,955</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from sale of real estate assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_55185738152449f5a1ca0896a71cbb64" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">254,083</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_efecf5285ea845a984a8c24b6cf68305" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Acquisition of licenses and other assets, net</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireIntangibleAssets" id="Fact_c4ddbc47fdde42a994020ac78cea3e4d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,378</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToAcquireIntangibleAssets" id="Fact_dff874e0a9d440f2b2291df63ce33c1c" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,946</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Purchases of strategic investments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsToAcquireOtherInvestments" id="Fact_80fc4ad369ea4266aa819342e5a274f3" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsToAcquireOtherInvestments" id="Fact_62fe3844a7e8414ea863aff8f888c1ce" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by (used in) investing activities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_f34b0cc23b5d447c95919927abae52a5" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">262,636</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetCashProvidedByUsedInInvestingActivities" id="Fact_25c5a36f9c66441bbadcb049e1be0f09" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">274,477</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financing activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_9766979c83c547faaf9db39fd1ec8b13" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,373</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_e8614ff277e9476fabd71fcec8d4876c" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,565</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_847a8383a3104ae19857ffdfc7350136" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">52,036</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_d0c63549a159422d8925dbeac4505a02" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,953</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_4420366a0a5648d6bb96c8031145c0f8" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,725</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsRelatedToTaxWithholdingForShareBasedCompensation" id="Fact_0355270d749349ec8d585f6e041767cc" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">13,411</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from the issuance of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1513b2e8ee8745e1a6d6ede2fdfd7366" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> percent</span> convertible senior notes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_4a615bd30cf04b2c8e3d6ef5f3655178" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_e572a2538ade494fa34b59c56be026f5" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">632,500</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProceedsFromConvertibleDebt" id="Fact_03ab8d471d1e4c8daa6066ec97f4dae1" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Royalty monetization issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:RoyaltyMonetizationIssuanceCosts" id="Fact_86ac2a31f4064519948f3c217ae5cc4d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">29</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:RoyaltyMonetizationIssuanceCosts" id="Fact_7f9d3ad8bb59482c8f121aa0796b6fe9" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:RoyaltyMonetizationIssuanceCosts" id="Fact_8c2ad446f0734abc8d91aca4a8594317" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cb89fb53ac9642199b9810bfb6bc7a9a" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> percent</span>
            convertible senior notes issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_c265ed167f6849ca802177191ecfe56c" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_71796689b9704e64b6e32c07bc23d966" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,609</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PaymentsOfDebtIssuanceCosts" id="Fact_373cff2ecd4749f3b5c73b03bbd03408" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Repurchase of $<span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_fa1e52e707f54f6db114f5d30479e534" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">247.9</ix:nonFraction></span>
            million principal amount of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_95c00692fc364b37b7d2eb40d0fd5a4a" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> percent</span> convertible senior notes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EarlyRepaymentOfConvertibleDebt" id="Fact_f70e21188bee4251b7e0cbbbb128a467" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EarlyRepaymentOfConvertibleDebt" id="Fact_6722f632b63b4e149ad0befd18fb572f" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">256,963</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EarlyRepaymentOfConvertibleDebt" id="Fact_e0141e05b2864bfcbb8b085c229eafa2" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Repayment of remaining principal amount of <span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1779ebfedc65406eb400aac2b614389b" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> percent</span> convertible senior notes at maturity</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_fb52319bb3e343a28dfb4c8402b73d68" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_e2c4d66efd61435abf43c876b223e173" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">61,967</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_dd36882e10e44acb8407f7c404b6f7bb" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Proceeds from issuance of warrants</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:PaymentsToMinorityShareholders" id="Fact_05f1061adaa04d2d8d88f3adc5ec6f7b" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">544,686</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net cash provided by (used in) financing activities</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_489978ad0a9b4acdb5c858892347ff39" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">592,719</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_323a2b839be44267a57618d86a42c961" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">471,527</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect" id="Fact_15eb19737eab4e538dc8c84af74c487a" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">285,623</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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</table>
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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest paid</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_6419ea93d02441d486308749fc3a69a2" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,898</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_2249909088154c1986cb1b79f68deed3" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,778</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:InterestPaidNet" id="Fact_8c17d62edf1c473d8eaf535bf23b8f15" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,247</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income taxes paid</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaid" id="Fact_c06db4a22c154dd4a32207c8b41d23bc" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,010</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaid" id="Fact_5318aab49def4a0f8b51981f5a454d31" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">38</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxesPaid" id="Fact_368f89931f0e430083f0bf01db6da5a7" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,855</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Supplemental disclosures of non-cash investing and financing activities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets obtained in exchange for lease liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_2e73a62ed6b94af4bbaf09f894de757d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">168,931</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_6738abc647624c90a0e3177ac78e71ea" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,641</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability" id="Fact_5c855545977c46e98693fab1376c9200" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,149</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts accrued for capital and patent expenditures</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:NonCashCapitalAndPatentExpenditures" id="Fact_7a2dfc2a1d1a4605b0263f1b76478acd" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,767</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:NonCashCapitalAndPatentExpenditures" id="Fact_f73d104fa14b4c6da9e22f41979ab811" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">705</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:NonCashCapitalAndPatentExpenditures" id="Fact_2e89ce6cc7c74c4aafae3dbbf97500c4" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,059</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
  <div><br />
  </div>

  <div><br />
  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">See accompanying notes.</div>

  <div><br />
  </div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">90</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><a id="Notes"><!--Anchor--></a>IONIS PHARMACEUTICALS, INC.</div>

  <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">NOTES TO CONSOLIDATED FINANCIAL STATEMENTS</div>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1. Organization and Significant Accounting Policies</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below
    <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_a88597664460426696b9ccf265c067d6" contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction> percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the
    period the changes occurred<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Organization and Business Activity</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us
    to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> determine which elements of the collaboration
      reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we
      consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our eplontersen collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue;
    while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as SG&amp;A expense and research and development expense, respectively.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the
    following criteria:</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
            contract; and</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div>
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    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We frequently enter into a collaboration agreement in which
      we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We
      evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we
      grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant
      discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do
    not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation. Refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Eplontersen Collaboration with AstraZeneca</span>, below for further discussion of a collaboration that included an upfront license payment.</div>
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<div><br />
  </div>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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  <div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
        agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments,
        license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the
        payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>
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  </div>

  <div>
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<div><br />
    </div>
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  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount
      method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include
      a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our
      milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain.</div>
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<div><br />
  </div>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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  <div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>
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  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the
      stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present
      value. The significant inputs we use to determine the projected income of a license could include</span>:</div>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div>
        </td>

  </tr>


</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div>
        </td>

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</table>
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of research and development, or R&amp;D, services by using our internal estimates of the cost to
    perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>
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<div><br />
  </div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div>
        </td>

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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div>
        </td>

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</table>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting
    guidance requires us to include a markup for a reasonable profit margin.</div>
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  </div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
        </td>

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</table>
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  </div>
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  <div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>
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  </div>

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    </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based
      on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given
      period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires
      us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>
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  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

  </tr>


</table>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
        </td>

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  </div>
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  <div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement
        and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services
        are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the
        amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative-effect adjustment.</div>
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  </div>

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      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93</div>

    </div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
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</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 Strategic Neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Our Revenue Sources</span></span>&#160;</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are sources of revenue and when we typically recognize revenue.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>
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  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA.</div>
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  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from
      SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began
    commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As
    a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and
    WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics
    companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In
    the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as
    distributors.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of
    the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
    view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
    distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer
    obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as
    selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as
    discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaboration agreements</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services and manufacturing services.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>. For each collaboration, we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation
      is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services.</span></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they
      are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in
      the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when
      we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
      recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone to the
      transaction price.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the
    milestone event and we do not have a performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">License fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is
      because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not
      have any performance obligations related to the sublicense.</span></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration with AstraZeneca</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the
    U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_798a2a15b8084859992f963edb75362e" contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment in 2021.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_e051c1fd4e944a92a8163d269956be81" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities
    that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_3cba0cc4bb2b4337844e4ffea49760a9" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation. For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_37318b29740c484b9341ea66122972eb" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_19aa95d597c248e5a38f0df2e0a747a4" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca
    related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively.</div>
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<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within one </span><span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a">quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022,
    approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_8cbaf7e8f6f14ab8b9a5bac9f1a94ee5" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">82.5</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_989b31e12c534c2cb51193d15fef47ac" contextRef="c20220101to20221231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> significant customer. As of December 31, 2021, approximately <ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_9b60e884ea4946728c18b631acdef31b" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">93.8</ix:nonFraction> percent of our contracts receivables were from <ix:nonFraction name="ions:NumberOfSignificantCustomers" id="Fact_5e1263191fc1438492a439c3f8e95b1d" contextRef="c20210101to20211231" unitRef="U007" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    significant customers.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen
    for SPINRAZA royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>
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<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2022 and 2021, we recognized $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">73.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ContractWithCustomerLiabilityRevenueRecognized" id="Fact_ced6b030f6d146bb91eabbce81e6f413" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">98.1</ix:nonFraction> million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the
    services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in research and development expenses are costs associated with our
    partner agreements. In 2022, 2021 and 2020, patent expenses were $<ix:nonFraction name="ions:PatentExpenses" id="Fact_85866a721e84472989175bb6188f4c57" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.7</ix:nonFraction> million, $<ix:nonFraction name="ions:PatentExpenses" id="Fact_a0ff596166e44c50ba79c8d446d1bb4e" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million and $<ix:nonFraction name="ions:PatentExpenses" id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.1</ix:nonFraction> million, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>
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<div><ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0173" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0174"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf333" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf334">
<div><br />
  </div>
</ix:continuation></ix:continuation>

  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0174" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0175"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf334" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf335">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0175" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0176"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf335" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf336">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0176" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0177"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf336" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf337">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0177" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0178"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf337" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf338">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0178" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0179"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf338" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf339">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0179" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0180"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf339" continuedAt="Text_517d5bc7baa3441594ab6b525c3adf3310">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0180" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0181"><ix:continuation id="Text_517d5bc7baa3441594ab6b525c3adf3310">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign
    subsidiaries. </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0181" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0182">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0182" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0183"><ix:nonNumeric name="us-gaap:EarningsPerSharePolicyTextBlock" id="Text_47e97970a2d74b528c3d5e13d3b65bad" contextRef="c20220101to20221231" escape="true" continuedAt="Text_909063b59b6348faad237e7ae63d2f191">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0183" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0184"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f191" continuedAt="Text_909063b59b6348faad237e7ae63d2f192">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0184" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0185"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f192" continuedAt="Text_909063b59b6348faad237e7ae63d2f193">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0185" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0186"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f193" continuedAt="Text_909063b59b6348faad237e7ae63d2f194">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0186" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0187"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f194" continuedAt="Text_909063b59b6348faad237e7ae63d2f195">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing the total net loss attributable to our common stockholders by our weighted-average number
    of common shares outstanding during the period. For the years ended December 31, 2022 and 2021, we did not have to consider Akcea results separately in our calculation because we owned <ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_f65a71d42ef046458f851b185dab48a4" contextRef="c20221231_OwnershipAxis_AkceaTherapeuticsIncMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction> percent of Akcea for the entire period. Our basic net loss per share for the years ended December 31, 2022 and 2021 was $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_a97fd98180da49a2889ec6c1d1bbecdb" contextRef="c20220101to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.90</ix:nonFraction> and $<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_07af0c67e7e142188bdb734757344850" contextRef="c20210101to20211231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.20</ix:nonFraction>, respectively.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0187" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0188"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f195" continuedAt="Text_909063b59b6348faad237e7ae63d2f196">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0188" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0189"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f196" continuedAt="Text_909063b59b6348faad237e7ae63d2f197">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the year ended December 31, 2020, we calculated total net loss attributable to our common stockholders using our net loss for Ionis on
    a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea. As a result of
    this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share was different than net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of
    operations.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0189" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0190"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f197" continuedAt="Text_909063b59b6348faad237e7ae63d2f198">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0190" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0191"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f198" continuedAt="Text_909063b59b6348faad237e7ae63d2f199"><ix:nonNumeric name="us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock" id="Text_6255ce3fc5024406b256c4e5a5be9dd3" contextRef="c20220101to20221231" escape="true" continuedAt="Text_d09ecd679d9b448d9d3246f07fa8de131">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):</div>
</ix:nonNumeric></ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0191" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0192"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f199" continuedAt="Text_909063b59b6348faad237e7ae63d2f1910"><ix:continuation id="Text_d09ecd679d9b448d9d3246f07fa8de131" continuedAt="Text_d09ecd679d9b448d9d3246f07fa8de132">
<div><br />
  </div>
</ix:continuation></ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0192" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0193"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f1910" continuedAt="Text_909063b59b6348faad237e7ae63d2f1911"><ix:continuation id="Text_d09ecd679d9b448d9d3246f07fa8de132">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-merger period attributable to our ownership</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:WeightedAverageNumberOfSharesOwnedInSubsidiary" id="Fact_b79e4cf71b194b0a94c2882b53cff812" contextRef="c20200101to20201031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">77,095</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_b89053da786941d6ae148fb509611a8f" contextRef="c20200101to20201031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">1.45</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_7b89782273294541a6a191e6add7cf9c" contextRef="c20200101to20201031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">111,775</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-merger period attributable to our ownership</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_d2978b9b35f846e297cf9df340b21ab9" contextRef="c20201101to20201231_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">85,987</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLoss" id="Fact_ca9bbb6fa2d6476682237132e18e3ea3" contextRef="c20200101to20201231_StatementBusinessSegmentsAxis_IonisCoreMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">246,702</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_129a4e0e3dab487eb3bebb6a384cf36a" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">444,464</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_a17f2512591d4e808cb7d0a9e321c747" contextRef="c20200101to20201231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">139,612</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_885ea3503dd64edf8316c0c40aa93e87" contextRef="c20200101to20201231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">3.18</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
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  </div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">97</div>

    </div>

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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent
    shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock underlying the following would have had an anti-dilutive effect on net loss per share:</div>
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<div><br />
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2458a3845ed24510a9f7ee91849cccfd" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_eb796a9cff164893992d0656c18cb133" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b26c82d7992442ff96c5568ee51f49f2" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f3006fbac4f149b38e6462396a20e208" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d9312f49e9424c82bffc13bbc2944526" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_6f2d97c4eb3c416a953a12543f2d88d9" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
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</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0199" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0200"><ix:continuation id="Text_909063b59b6348faad237e7ae63d2f1917" continuedAt="Text_909063b59b6348faad237e7ae63d2f1918">
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_94aea085060d41bc80cec7916b6f1fdf" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_313a82c8d6674d4c8879cbc00534b803" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1f4d9d777dda40daac28b07c65d54061" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_e1e4ce6d99304ee2869dcb8f7128390e" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_249642bbc67c4af8aee0dce96615e1db" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_95124792ec6b4cf2aea843897e0bc1e9" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction></ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ab2ca98eca3b41c39251369e1b0f26ff" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a16fb6d3f6564b33b6f016caae75ec6f" contextRef="c20201231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_473b165882ea47afa1e8a91eff34239c" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction></ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

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</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>
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    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022 and 2021, common stock underlying the following would also have had an anti-dilutive effect on net
    loss per share:</div>
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<div><br />
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_73bfeee93f8546f5b370edd9f616a4d4" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5c056baf11664eb8bb1412c9ff380ed0" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_769655fa2afc4791b0ea57ec99a02fed" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_27a4ad482c384321b81448144513139e" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes; and</span></div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_1c6dd4aa81824cad8f86c21b0cbc10a0" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8e8c26f5c9244588940e55bdaee73dca" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes.</span></div>
        </td>

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</table>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of December 31, 2022 and 2021, we had warrants related to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5e58b95589c84ac9b547f68765b4e7c6" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3705d19197a048d39639dc989c41b309" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_3ff6581e719f484fa5f31e462a6f100e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4f435167735248eb8f2c138c463d6dfc" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction></ix:nonFraction> percent Notes outstanding. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_b4d09574c5df412aa2e3ca9444baf598" contextRef="c20220101to20221231_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7790526b5c3648779a4130225f212db9" contextRef="c20220101to20221231_AwardTypeAxis_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" format="ixt-sec:durwordsen">ten years</ix:nonNumeric> for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended
    December 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected
    term based on our historical exercise patterns.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9c07a9a996a942cfa5196c4e73d65a5f" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementEmployeeMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_a9d4677fe482460496896805b6e948d8" contextRef="c20220101to20221231_AwardDateAxis_GrantedPriorToJune2020Member_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. RSUs granted to our board of directors after June 2020 fully vest after <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_317dd58aff2644f5948252ec0ede060a" contextRef="c20220101to20221231_AwardDateAxis_GrantedAfterJune2020Member_AwardTypeAxis_RestrictedStockUnitsRSUMember_GranteeStatusAxis_ShareBasedPaymentArrangementBoardOfDirectorMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span> of the PRSUs may vest at the end
    of <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" id="Fact_4556558cf7c146f081140dde2cf15e02" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U008" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> separate performance periods spread over the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_9ee4b8f0d0fc415d8fedacb7e025157a" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" format="ixt-sec:durwordsen">three years</ix:nonNumeric> following the date of grant (i.e., the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_4a3b1878ccda46faa7e3dcc5b7ecf3f1" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one-year</ix:nonNumeric> period commencing on the
    date of grant and ending on the first anniversary of the date of grant; the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_10bf9fa3aeef4afaa6e49f9def9210ca" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheTwoMember" format="ixt-sec:durwordsen">two-year</ix:nonNumeric> period commencing on the date of grant and ending on the
    second anniversary of the date of grant; and the <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_cb84749fad7546409795da36a9b7b020" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_VestingAxis_ShareBasedCompensationAwardTrancheThreeMember" format="ixt-sec:durwordsen">three-year</ix:nonNumeric> period commencing on the date of grant and ending on the third anniversary of the
    date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" id="Fact_ff5f5a5a72cb44c38314ac19e661c09e" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember" unitRef="U002" decimals="0" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_b0b7848e22764764b4bcbddd5a2927ff" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MinimumMember" unitRef="U003" decimals="INF" scale="0" format="ixt-sec:numwordsen">zero</ix:nonFraction> to <ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" id="Fact_1370c49d2caf4b69b350f951933b5194" contextRef="c20220101to20221231_AwardTypeAxis_PerformanceSharesMember_GranteeStatusAxis_ExecutiveOfficerMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">150</ix:nonFraction> percent of the target number
    depending on our relative TSR.</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>
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<div><br />
  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217;
      Equity,</span> for additional information regarding our stock-based compensation plans.</div>
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<div><br />
  </div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>
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<div><br />
  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Merger
      in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_1097de361427408da42d756b10b489be" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MinimumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">68</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><ix:nonFraction name="us-gaap:MinorityInterestOwnershipPercentageByParent" id="Fact_5665dba820d74eba9e6f5307d4168e81" contextRef="c20201031_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">77</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of
      Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Merger, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line in our
      statements of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheets. In addition, through the closing of the Akcea Merger, we recorded a noncontrolling interest adjustment to account for the stock options Akcea
      granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
      compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>
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<div><br />
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other Comprehensive Loss</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):</span></div>
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<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br />
  </div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_6f30e6b32fc54ac29484f539ce291bdb" contextRef="c20211231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,668</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_19707e9f0bad40fbb1dba6349904c9f1" contextRef="c20201231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">21,071</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax" id="Fact_8b6552c5f5c94eabb610231c0a6f2229" contextRef="c20220101to20221231_StatementEquityComponentsAxis_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,395</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax" id="Fact_f4bc7becd02b4abe8419122ceb5ec217" contextRef="c20210101to20211231_StatementEquityComponentsAxis_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,486</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" id="Fact_87cd5d2b3825448daf6f69c617a273ab" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">127</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive income (losses) for the year</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossNetOfTax" id="Fact_2ce128cedcb64e06a3c8d4d1586e4c6e" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">24,812</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossNetOfTax" id="Fact_a2223b8bb7e44f6f89e44f7a99d65ec1" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">11,597</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossNetOfTax" id="Fact_15d14efe39a949dabe720e0cc4f8a8d2" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,219</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_47d26dc5eb544c51b35c31726e80cf7c" contextRef="c20221231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">57,480</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_92c6a81d4cc548c79c16aa702d293bfc" contextRef="c20211231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">32,668</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" id="Fact_d50f6f2316fb42a59ada44dcc1e3f6fc" contextRef="c20201231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">21,071</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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  </tr>


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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
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            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c173053f21eb48f2baac71e2bf36f606" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">We did <ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_8a44be227c064d7eaec920b423ef7df6" contextRef="c20210101to20211231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_51731348898e477f98ddd1af36189c22" contextRef="c20220101to20221231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:OtherComprehensiveIncomeLossTax" id="Fact_c02531ea3239480789cb50bedcd8d654" contextRef="c20200101to20201231" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction></ix:nonFraction>t have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.</ix:footnote>&#160;</div>
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    </div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">99</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
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<div><ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0248" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0249"><ix:nonNumeric name="us-gaap:ConcentrationRiskCreditRisk" id="Text_2657526565084c29a44990225a255af0" contextRef="c20220101to20221231" escape="true" continuedAt="Text_c2ce41bc5e7e422ea9e5ba234cef3c9b1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>
</ix:nonNumeric></ix:continuation>

  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0249" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0250"><ix:continuation id="Text_c2ce41bc5e7e422ea9e5ba234cef3c9b1" continuedAt="Text_c2ce41bc5e7e422ea9e5ba234cef3c9b2">
<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>
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  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0259" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0260"><ix:continuation id="Text_8258dfb287b64b0781bb248a3f52b4593" continuedAt="Text_8258dfb287b64b0781bb248a3f52b4594">
<div><br />
  </div>
</ix:continuation></ix:continuation></div>

  <div>
    <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0260" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0261"><ix:continuation id="Text_8258dfb287b64b0781bb248a3f52b4594" continuedAt="Text_8258dfb287b64b0781bb248a3f52b4595">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we
      received as part of a technology license or partner agreement. At December 31, 2022, we held equity investments in <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_b448547c88c7434cbc329f97a4b3ea28" contextRef="c20221231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly traded companies and <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_5091e6339b9e4e85943dd42b9d332383" contextRef="c20221231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction>
      privately held companies.</div>
</ix:continuation></ix:continuation>
  </div>
<div><ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0261" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0262"><ix:continuation id="Text_8258dfb287b64b0781bb248a3f52b4595" continuedAt="Text_8258dfb287b64b0781bb248a3f52b4596">
<div><br />
  </div>
</ix:continuation></ix:continuation>

  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0262" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0263"><ix:continuation id="Text_8258dfb287b64b0781bb248a3f52b4596">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment
    of the same issuer.</div>
</ix:continuation></ix:continuation>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0264" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0265"><ix:nonNumeric name="us-gaap:InventoryPolicyTextBlock" id="Text_962b0a89596444369c91918399edde59" contextRef="c20220101to20221231" escape="true" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0265" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0266"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d1" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d2">
<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0266" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0267"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d2" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d3">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in
    inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and,
    as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We
    expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial
    medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0267" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0268"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d3" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d4">
<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0268" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0269"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d4" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d5">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical
    write-offs.</div>
</ix:continuation></ix:continuation></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div>

    </div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

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<div><ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0269" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0270"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d5" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d6">
<div><br />
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</ix:continuation></ix:continuation>

  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0270" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0271"><ix:continuation id="Text_0487e3a7deb14f71a5fc93f81023bf5d6" continuedAt="Text_0487e3a7deb14f71a5fc93f81023bf5d7"><ix:nonNumeric name="us-gaap:ScheduleOfInventoryCurrentTableTextBlock" id="Text_42918dc083b14298bf3e140fca4a1e1b" contextRef="c20220101to20221231" escape="true" continuedAt="Text_3dea8cc1e5dc47729e6497f2120162e91">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>
</ix:nonNumeric></ix:continuation></ix:continuation>
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<div><br />
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

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<div style="text-align: left;"><br />
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;">
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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_56a2f9f0147240f0bd015bba6bf7acb2" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">-</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_48464f6662f34caab0d0adfeb2d1483a" contextRef="c20211231_PropertyPlantAndEquipmentByTypeAxis_LandImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,077</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:PropertyPlantAndEquipmentGross" id="Fact_9274143ded5b4f0ba33136edf1a5c107" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_LeaseholdImprovementsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">28,357</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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  <tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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  <ix:continuation id="Text_d158cd1423c747408fc7f85b78e4dfe0280" continuedAt="Text_d158cd1423c747408fc7f85b78e4dfe0281"><ix:continuation id="Text_99f3d0319eab4a29bcbe167ddffaefa76" continuedAt="Text_99f3d0319eab4a29bcbe167ddffaefa77">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we sold the facilities and related land at our headquarters for net proceeds of $<ix:nonFraction name="ions:NetProceedsFromSaleOfBuildingsAndLand" id="Fact_012f50141a75474c9ea01d7bcfcc65ec" contextRef="c20221001to20221031" unitRef="U001" decimals="-5" scale="6">202.6</ix:nonFraction> million in connection with a sale and leaseback transaction.&#160; In connection with the sale of these real estate assets, we de-recognized the related land and improvements,
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>
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<div><br />
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedInLicensingFeesCurrent" id="Fact_a1182bff6aa841d1b17861b49376378a" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,044</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedCommercialExpensesCurrent" id="Fact_991e082179bb4e87b5afb60cdf56fada" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,498</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AccruedCommercialExpensesCurrent" id="Fact_dce6ebe7c0d64208a814a92b3849fcba" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,471</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other miscellaneous expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAccruedLiabilitiesCurrent" id="Fact_36801832e43e415bbc066744d39ceba6" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,198</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherAccruedLiabilitiesCurrent" id="Fact_558a2514ca9d46d38ef6431a99ec3875" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,315</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total accrued liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_d3d4336195b54976b7bcea8d3b30b7ac" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">140,101</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AccruedLiabilitiesCurrent" id="Fact_e91e73e81dd74acab89c06a66144eab3" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">88,560</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Costs</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, we had <ix:nonFraction name="ions:DebtInstrumentNumberOfConvertibleNotes" id="Fact_10f5114021fc4f5bb04196fe30354c8a" contextRef="c20221231" unitRef="U010" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    outstanding convertible senior notes, our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_88cf15606ae648ba879a91ce9224095e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, which mature in April 2026, and our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_637081ace1c3467395b29f412ee7c215" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes, which mature in December 2024. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, for further details on our convertible senior notes.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fe2e410b891c4e8f90e9c7af0b2fd97c" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ad09e792f7534196a47d6e0a5fba48da" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives
      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify the
    note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an
    aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_33bc30118e9548358994c912eadf2161">single</span> operating segment. Previously, we had operated as <ix:nonFraction name="us-gaap:NumberOfOperatingSegments" id="Fact_a315f651d2c042c59a48e5688cd8c8d7" contextRef="c20200101to20201231" unitRef="U011" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div><br />
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities
    subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity
    securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter
    of 2022. This guidance did not have a material impact on our consolidated financial statements.</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
</ix:continuation></ix:continuation></div>

  <div><br />
  </div>
<div><ix:nonNumeric name="us-gaap:InvestmentTextBlock" id="Text_9571e0c61df44815a452af9dc71349ef" contextRef="c20220101to20221231" escape="true" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a0371">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Investments</div>
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  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2022:</div>
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<div><br />
  </div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a0389bbbc04d444aa9945a16f2f77b47" contextRef="c20220101to20221231" format="ixt-sec:durwordsen">One year</ix:nonNumeric></span>
            or less</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" id="Fact_e1a84f7ba1234915827448c633c10e96" contextRef="c20221231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">70</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange1" id="Fact_a9a809b245674eb5912c14df728dc0f0" contextRef="c20220101to20221231" format="ixt-sec:durwordsen">one year</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_d1dd3aa1c3444cc8babea1f02c42cb74" contextRef="c20220101to20221231" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" id="Fact_54f16a3082454b16a1368f8660393627" contextRef="c20221231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">28</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;"><ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_649df9025a904bcfad6dc6ab6bd4c304" contextRef="c20220101to20221231" format="ixt-sec:durwordsen">two years</ix:nonNumeric></span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" id="Fact_d60e9c8e586b428c886b9d9653ac0f6e" contextRef="c20221231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" id="Fact_298fc5ad20a2442399af2cd8e8215ece" contextRef="c20221231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at December 31, 2022,
    <ix:nonFraction name="ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" id="Fact_971b070bcf6846b8970847cdbaef1457" contextRef="c20221231" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">98</ix:nonFraction> percent of our available-for-sale securities had a maturity of less than <ix:nonNumeric name="ions:MaximumContractMaturityPeriodRange2" id="Fact_e4aa3be8fcd040d0bcd0def824af337d" contextRef="c20220101to20221231" format="ixt-sec:durwordsen">two years</ix:nonNumeric>.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At December 31, 2022, we had an ownership interest of less than 20 percent </span>in <ix:nonFraction name="ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_c487d989afb240aaae9be0536d4b8656" contextRef="c20221231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">eight</ix:nonFraction>
    privately held companies and <ix:nonFraction name="ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee" contextRef="c20221231" unitRef="U009" decimals="INF" scale="0" format="ixt-sec:numwordsen">three</ix:nonFraction> publicly held companies with which we conduct business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div><br />
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">103</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2022</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_bc9e70d55b674cc9b6be541478de94e8" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">513,790</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_0c24393396f14a5fadd7e6d9dd062834" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_615e6981ef5c43e4afa6a302941c0754" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,365</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_0a185c2049a6469e81e8e4df671bb2f5" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">509,448</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_c9d17af33c554c64ac738dfbdb48494c" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">133,585</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_e61b3c1e7a7a45d7a7ce7d512404dfea" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_8cd5ebaff4ff47b59a6f49c94f90f5e4" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,829</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_dc66d2f463f54767abee4fc4f62595f6" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">131,756</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f00bcd75b4b842ec98fdc045c48c2576" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">512,655</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_d6b1880a34fc425f848f593694e21d3b" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_52ee12eba4604cd6beb6d916ef074d49" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,124</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_93f61f2dcaf249fe8c2941b0bedb2ad6" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">507,554</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f17e37bd45aa4fdbae4827a34aa7dac9" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">57,484</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_8da02b683fe94c99ae3334fe0583bcbf" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f5548b5e22d64358b14bff13c4cde745" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">686</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5215ece6e8674be582ac13fad8e0e02f" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,816</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_c43846612e6447abb7c0b4a78b53c4e8" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,008</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_00f6f92014f542349f4a8a623b4469ca" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_72f682b37c6245c08c753c36256c8420" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_9ea39aa66ae74e5f8b3f54b59a80dad0" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,994</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_06b37f3d76b24645b428aed40ef7519d" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,223,522</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_68c90e44ae7142faa5c935422fe6ca01" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">227,631</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_8078467ba1d947589f274b1470ccc8c7" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">217,502</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_e4c79d28e0dd438c896e0c5148cdbae0" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">34,339</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_c3fb53b35b5e4f0a801fb17377bbe452" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_f20247b6d2f84ccbbb1dbab68b9cd3d6" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,040</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_a656c02b450b4ae39000dbd1d10a2d67" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">33,299</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_160b2612c5ff403daa0b23ecdd2866db" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">245,030</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_b1272ac8ac42497ba65853e630ea020a" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_803581e2009f4b95bf2af6ab10413c74" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,109</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_32fdcfaa188c4467a9bc336b98ee4765" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">240,921</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_4ae16ba11af3451383afc794f381425b" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_fee237831c094d6db8d66deaea062f6b" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">116</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_b46d7b7d41284f92910e48dd0d37da98" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">329</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_072a76897a5042d8befaddf252441541" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,101</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_b71803caad4d4886ad41f6bbc5e209f5" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">525,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_8a0a49d9cc1e4c129249d0be27e415f2" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">130</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_0ca92b9c73b2492aadcfbe4f82a50cb4" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,621</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_91167061047b48f4b8610c1a21447584" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">509,823</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_a5e37551797746d7832fc5653898ad64" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,748,836</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_5784263002924b25aff1cb14f626bf7f" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">194</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_7654b51ce0a5448fa1c5723b77e4a3cd" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,639</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb3ebfc0325446129501360d15bf62ff" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,721,391</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_cef09f69ddec4b3dabee2b4ce3e2377b" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_3f654be6d96e41e4b4713c77ccf1c8e3" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_3d2a388042994347ab5102d669861a7d" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_2d87969d9ae34d49b910e43cebb1d676" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,539</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_9ebd36323e384809b15acae0a3551932" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_aed73c2c4de9479b940ffa549e9fedd0" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,257</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_1f1394dc79044e9197f515e0b7bca042" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_acab1218ec2e41199e1b320128741143" contextRef="c20221231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">40,372</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_1f62fdc7a62342f68a33d50b3bde0a58" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">35,012</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_c2b1f14b00d941b6b317ee97742c8d96" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,257</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_9d1928afc7224324b66d25fddff38253" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,358</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_594521b1bd6241bea5eaec95f58271c0" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">50,911</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_afee4ce7ef954363a1010e810f1ae960" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,783,848</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_a346c4f456874316909407a757ecc1b7" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">17,451</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_f35d561e61484f2295cadeeb2d03bdbd" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,772,302</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation>
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<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03717" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03718"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b4" continuedAt="Text_69285505f37c4c39a4637ed71508374b5">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_8ea119980dc64034994a6b7ad86f848c" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">383,870</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6df2fbe2752e4bd0bb77abf8abe0ae29" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">728</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_73421ff544c5487b9e733e95b060b569" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">226</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_c85091a5a55a45a881f09b4c8c70a29c" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">384,372</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_da1b311c89004135b55ecee7befa549d" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,493</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_6c6ca7c3257b46848b5da442e9d2b424" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">19</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f8696120bd5749f081186004728dcfec" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_ba83c8acf52443779871f0f7f21e0f69" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">48,494</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_267f46317f0b40caa2f037611c038a1e" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,424</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_2d25c6a792494377addd272a5b8dded6" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_f56cc4d0d90d4e7fbb8f72585969858c" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">64</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_0c7a5d61dae34de8a30b14b8802b8785" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,360</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_2665cd241db44217ad8643b9ae2a63da" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">134,770</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostCurrent" id="Fact_f91f4bf7895e4255b6fb1606547e04c4" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">612,557</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent" id="Fact_58f014330e0d46f68ac56681d9bcc775" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">792</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent" id="Fact_4d687e924d2549c292e3b98c471a8b1c" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">345</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesCurrent" id="Fact_5b653caa5875494f883c075c43b1bf5c" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">613,004</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_90b66da8071a4a14ae79ae20e35a4725" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">382,000</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_6969869c8ab34390a5923698c47c72bb" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">331</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_fa5a358807714f81a4468c02e061a381" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,644</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_c8341442a25e450b8c2a53f28afa5bbb" contextRef="c20211231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">379,687</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_627bd1dd191a4e2aa0ffcac3c093515e" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,935</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_de7b01c6aeff4c67be7342b578227fe7" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_6dd609ef5c9d4c5abd47201f2f3c3971" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">561</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_01ade62c43ae4d1d9d121b813ab06110" contextRef="c20211231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">72,374</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_1a4e37f7b16f498caa99b193ac3977d1" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">137,635</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_9e774f36b3824b5da1f596ef542f70e8" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">139</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_fcf3826f90e44039b289f8286697222d" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">500</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_3834f60c806146fdb57604df4ca44d5f" contextRef="c20211231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">137,274</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_3b50fc36268c472c83543a498f74c6a3" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">39,909</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_3cc6fe9c6c684eabbb359b5b57a83381" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_f9f79be238454b459039ee2cf29f6635" contextRef="c20211231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_4bf9121fc0804d5798d1a6289635f5d9" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,136</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_f437f12df65d447e97fa0d457cb8cef8" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_c0f6ebbcda8044b09f9d090885923686" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">37</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_c14671d2b253484ead01fa457d0f93ee" contextRef="c20211231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,099</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent" id="Fact_be05404e83c643348777fa91b0e1b9ba" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">638,615</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent" id="Fact_80c5acbabb8c4f0bb30f07636779a6ef" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">471</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent" id="Fact_2d2b1cb797c643148d37d334e933eeb2" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,966</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecuritiesNoncurrent" id="Fact_2bbc29a667a94cb99ff6c9f040ebeea6" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">635,120</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAmortizedCostBasis" id="Fact_8caafd476a3541b9aef7c098cc041e94" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,251,172</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" id="Fact_609132a66d2f4130b140a88c2fb0c89d" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,263</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" id="Fact_b09e4761e6054b25a622ed40b8db284e" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,311</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_4de7d9b3be6d447db4b3c3fe0b8f036b" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,248,124</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_ddb646a5d0f1447b92caf9f07a627fcd" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,897</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_88ed4a2745c54e14a622755a003ef7d5" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,145</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_b4cdd38512ef47d9b5d3df0de25143e1" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">837</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c71d4b805e374b9696b1907d0c3b8708" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,205</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_fd07a2a1606f48d78bc5fb285d90a137" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,615</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_f166a5e138d3457b82d04bfee0b2aaa8" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">16,707</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_250e88ec455a48818d6c542e743f1801" contextRef="c20211231_FinancialInstrumentAxis_EquitySecuritiesPrivateCompaniesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,322</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNiCost" id="Fact_8cbb173fbf424d2cae5761cfe86aa386" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,512</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain" id="Fact_c7bf32577ac44c999892ccbf176d194e" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">23,852</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" id="Fact_7050ac2adf394b31b986c11c8b0618f6" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">837</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_b3f9adef6e924b3c91c0bc0573208fed" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">50,527</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost" id="Fact_c31aca2dbed748588049458efeea09a7" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,278,684</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain" id="Fact_c255d1502e344319b6e94f49f85ceeb8" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">25,115</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss" id="Fact_442681fd5f144b86afca5af925fffb02" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,148</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi" id="Fact_59bf550c30564d83b459e349c7ec3c12" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,298,651</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03718" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03719"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b5" continuedAt="Text_69285505f37c4c39a4637ed71508374b6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03719" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03720"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b6" continuedAt="Text_69285505f37c4c39a4637ed71508374b7">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_88fe67a8cca841eaa8660167eec626fe" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Includes investments classified as cash
            equivalents in our consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03720" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03721"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b7" continuedAt="Text_69285505f37c4c39a4637ed71508374b8">
<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03721" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03722"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b8" continuedAt="Text_69285505f37c4c39a4637ed71508374b9">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_33f87045331d4d29a03153170558d0a1" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $<ix:nonFraction name="us-gaap:EquitySecuritiesFvNiUnrealizedLoss" id="Fact_97381c7c87c2484fa19e43717dc354ca" contextRef="c20220101to20221231_FinancialInstrumentAxis_EquitySecuritiesPubliclyTradedCompaniesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.7</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized
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  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03722" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03723"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b9" continuedAt="Text_69285505f37c4c39a4637ed71508374b10">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03723" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03724"><ix:continuation id="Text_69285505f37c4c39a4637ed71508374b10">
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_92f3ab0ee45a44b9baf44a6e4c6792b4" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus
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              sheets.</span></ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation></div>


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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104</div>

    </div>

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<div><br />
  </div>
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  <ix:continuation id="Text_7833efd7812340cbb7bf4ba3c0f5a03725" continuedAt="Text_7833efd7812340cbb7bf4ba3c0f5a03726"><ix:nonNumeric name="us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock" id="Text_abfd8de3bb27493b80611f0ca9f4f478" contextRef="c20220101to20221231" escape="true" continuedAt="Text_07d003c6978748ba9cb47dd28ec1f4ea1">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be
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      All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more
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<div><br />
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_f4a5c25e37b543f7932cc0d01427eb2b" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">384</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_8e48e186979f4b918d2edbccb3d5b01c" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">384,136</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_7fdf176baf4d4864ac3a9538410eb63b" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,629</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f35695329a0a47938d27089c6693459f" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">305,367</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_7e9108673c6f481cbe3b9965b6cfd9cb" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,879</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_8fb2ae4a1ec045fa9a3e85eb73fd7579" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">689,503</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_324d1ca3c5b04a21a80ffb6c2a84d43e" contextRef="c20221231_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,508</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_470fc8ee60a84e25b6fc08a2cbb85990" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">48</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_aeff41705ae349b29427d35a8d443bf7" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">93,862</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_8fba36c97e7d4a80a1ae60c439a9af03" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">538</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f657b8c8ce234a3daf422cd98844996b" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">70,233</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_125efbdc4abf453ea61824f7f8dfcbdf" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,331</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_2fbf57c2ffa245f294b609d611c85a62" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">164,095</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_cbfbf344402746efbb0dcac0962c7ce3" contextRef="c20221231_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,869</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_dbb0a900723b4e209ffa74a517efd053" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">75</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_39c3036d6aee4e01b4a3ae672c4b0896" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">616,826</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_40dcd840d1a240968fdca65e541675b7" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,082</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_f5da7f349913446f8c02b0bf6053fd09" contextRef="c20221231_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">86,325</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; white-space: nowrap;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_71c2fda61dc846298eeff9b0ca38115c" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">110</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_6990d89425474cfc9c4b8bf0d8cf7439" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,117</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_4a48d7c90c5a4a0bbe2ae5be47316023" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">225</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_a28ea3274df5428e98f07b9d17b49fab" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">31,465</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_687e88a52c8446078d869df0c183470d" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">790</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_c17115e0327d4b7ca7c6e3aadbaaf14f" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">49,582</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_8c469d84d7df46f7a259af6e5d56319a" contextRef="c20221231_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,015</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_4525776b9a044ddea7215ff94525fd5a" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_2e10a06daa13405bb29576b077fe673e" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_f5666df468b14ae3b46bddbb87780254" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_e3af88029717408894b13c5d18baba2e" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_7d37f1f73b464197979c53a728b05239" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_c0f25eb6a32b46679f2cd4a9ec178179" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,993</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_6c513112140946e994a33c9b4fc45430" contextRef="c20221231_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions" id="Fact_c5a13e110d15472bb7209a893f75760c" contextRef="c20221231" unitRef="U012" decimals="0" scale="0" format="ixt:num-dot-decimal">619</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months" id="Fact_bcffdf58f44a4915b5c47f23299cb0a4" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,112,941</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss" id="Fact_258d034cad9c41d5818f3ff1c5e9ac54" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,474</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger" id="Fact_8d829588e22141b8a62fed91d7622b5e" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">499,383</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss" id="Fact_36b440f266f44cfa9a6ffb88f94ffc3f" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,165</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPosition" id="Fact_29ce681916874294a263914fba442f04" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,612,324</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" id="Fact_c6330165fcf44008a4bcbadea16125b1" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">27,639</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation></div>

  <div style="text-align: left;"><br />
  </div>
<div><ix:nonNumeric name="us-gaap:FairValueDisclosuresTextBlock" id="Text_a080c2e549ed48798336fbfa516a174a" contextRef="c20220101to20221231" escape="true" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Fair Value Measurements</div>
</ix:nonNumeric>

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  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.</div>
</ix:continuation>
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  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2022 and 2021&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. As of December 31, 2022, we did <ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_a988bf8349494d7c8d4820caa5216c6f" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt-sec:numwordsen">no</ix:nonFraction>t have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy
    of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa6" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa7"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff72" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff73">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_436883975bf3468b92c09cc61e03fa41" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">211,655</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_79dfa1d423f642cea572a5bb9c411e6e" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">211,655</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_65c74896addd4b7890c68f56ab5c5f70" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_bd40b54476544609af8d4027bb17852a" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">726,950</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_47015bf7b4364a728c529aec5394713b" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ce2106e4180b41eb85df7504ba1e6268" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">726,950</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_b9f55a2040604cca8871949edbe9c0ea" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">165,055</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_86e4aa20eea74f8787ba658ab420d933" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f735c515b82742aeba74bdbab4e4e4a5" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">165,055</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f597ef484dc849b3869c0b24b7e47ca0" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">748,475</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_d4426d3c42f14b8c87105791656383d6" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">748,475</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fbe819f745134bb9b6fee8629da4b647" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_8508dcfab1e4444dab865f21eafaac04" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,917</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_85146eb5ada740ee9a53b19db08fdc47" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_a2f79fbed84d4f169900f21d26a0c14b" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">74,917</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2a054eacb3c24df2a8c4b1f88bf0acac" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,994</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_2113772730b344d3984359add01d7533" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_087f87a36eb44396bc61d8397c8a298b" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,994</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_3a7b94ae1575483d99cdff167336737c" contextRef="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,539</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_dcbce3ea27dc430f9082c8d96ba2c86b" contextRef="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,539</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_9b2894878d734371a537f270d1142205" contextRef="c20221231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_41aa8ca715a246c6ab132f68d33110c2" contextRef="c20221231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,943,585</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_14262b51a03546e9864249ccb9ca4a20" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">970,669</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_8134fdf4a60f4810b009f807fc4ce04e" contextRef="c20221231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">972,916</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_6f9a8b7bb0274b6aa4ebdbfd8ec1cda4" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">541,199</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_d022e13f5bfc44a485ff5fc107b87349" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">541,199</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_0dd4548c72224cd6975d2b0c28babec7" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CashAndCashEquivalentsFairValueDisclosure" id="Fact_8f545818449344c6aa7d6c5c434904d3" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_15e5c1c8e15b4ec985dcee227484669f" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">764,059</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fb9b7215206045289d5ac989482b34ac" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_9e1bc60cb2a5438ba5a8181266e5e834" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">764,059</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_62d3bc177e034c67a0364f8cffcd9eab" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7b7ffacc071c46e28e5bc02c6cbdf406" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,868</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f00f0183fbdb414bb8ace8c09326de91" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_6bff7c97ac774c11923e8315e813ef18" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">120,868</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7b492acc2ddf47d39f228955b0b370a4" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USGovernmentAgenciesDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_3f43d316784545c8b69beec4e9b1bf54" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,634</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_9f168d9ee16e4f3b813f38c507fa28b1" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">182,634</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_0e067bc23c4d4301839ded59e2581b10" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_fae3d9745ad145d180fd60e4e2f3ab73" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USTreasurySecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_f4d1d69ba9254d3b8aff137c28df29e2" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">174,464</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_7ea5abb7b7dc46d8b9f0f873e9607020" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_e8c040876cb94663b41bc3252cdfe50f" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">174,464</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_09a165a8a1724ba2b86344737ccf7a04" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_USStatesAndPoliticalSubdivisionsMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_1d6ec00c78964c999451adb81d4c60a2" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,099</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ba6ea93809db4df2be5272d7fb3a6008" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_c660da70931c462ba2056be05730a5c3" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,099</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_169a436760844aa3a860d5bc7377c977" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_OtherDebtSecuritiesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
          </div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_37704b09f78f4b92a28ef1c4adab51e6" contextRef="c20211231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">18,205</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_c115b34d583a44a29382311b1404da7b" contextRef="c20211231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,875</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_8bfd913d5c5c43aeb9ae030ed40f9b2c" contextRef="c20211231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EquitySecuritiesFvNi" id="Fact_04d637ffa4c949d797e25d4f0f8ef237" contextRef="c20211231_BalanceSheetLocationAxis_OtherCurrentAssetsMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,330</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_57c8091a5a114c3c8f6bccd694eb8b0e" contextRef="c20211231_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,807,528</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_9efce47d082648b086daa33248918cfb" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel1Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">727,708</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_45cbd4a07e9d4ab8b914ee2d30888ee9" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,065,490</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AssetsFairValueDisclosure" id="Fact_be2accdcf50a4950a5d255ed65a9969b" contextRef="c20211231_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel3Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,330</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa9" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa10"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff75" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff76">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa10" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa11"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff76" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff77">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_ad43559c353f456eac7c04729a412d6f" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in cash and cash equivalents in our
            consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa11" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa12"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff77" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff78">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa12" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa13"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff78" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff79">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_77eb85d4142a44a68a7c6b25a7169d1c" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in short-term investments.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa13" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa14"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff79" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff710">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa14" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa15"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff710" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff711">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_cc6012bb3041434399bdb287399a913a" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_ce470ce0da684fc0965a0abdbc5bdb8f" contextRef="c20221231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa15" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa16"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff711" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff712">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa16" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa17"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff712" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff713">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_f0e1d58ea08e4b55a4c7703dd1e397d3" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Included in other current assets in our
            consolidated balance sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa17" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa18"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff713" continuedAt="Text_2c90dd9c83154e049f580be3a5998ff714">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa18" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa19"><ix:continuation id="Text_2c90dd9c83154e049f580be3a5998ff714">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c498c367d1f949d4a789172bf48c4121" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">$<ix:nonFraction name="us-gaap:AvailableForSaleSecuritiesDebtSecurities" id="Fact_901bc85a32f541369ef5a8de46f7eb74" contextRef="c20211231_BalanceSheetLocationAxis_CashAndCashEquivalentsMember_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember_FinancialInstrumentAxis_CorporateDebtSecuritiesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.3</ix:nonFraction> million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>

  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa19" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa20">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa20" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa21">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>
</ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa21" continuedAt="Text_bbc03e6d583a4688b265ebc069c1a3fa22">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_bbc03e6d583a4688b265ebc069c1a3fa22">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bd322b8313e14411b434a697d8be9cf3" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_47cf6f98169049fbac9d864c715e8edb" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes had a fair value of $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_4dd54a5e498144848bb917146895383f" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">498.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:NotesPayableFairValueDisclosure" id="Fact_f0e3f2364810404e841460fd9d182b2b" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember_FairValueByFairValueHierarchyLevelAxis_FairValueInputsLevel2Member_FairValueByMeasurementFrequencyAxis_FairValueMeasurementsRecurringMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">587.3</ix:nonFraction> million at December 31, 2022,
    respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
</ix:continuation></div>

  <div><br />
  </div>
<div><ix:nonNumeric name="us-gaap:DebtDisclosureTextBlock" id="Text_1f7799e29d9c4fd5ac2c30d64ad9a625" contextRef="c20220101to20221231" escape="true" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f1">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. Long-Term Obligations and Commitments</div>
</ix:nonNumeric>

  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f1" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f2">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f2" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f3"><ix:nonNumeric name="us-gaap:ScheduleOfDebtInstrumentsTextBlock" id="Text_a4959bdb175f4cf6a490ada2282e4021" contextRef="c20220101to20221231" escape="true" continuedAt="Text_59232552a526469d8af3344cc1ee26461">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f3" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f4"><ix:continuation id="Text_59232552a526469d8af3344cc1ee26461" continuedAt="Text_59232552a526469d8af3344cc1ee26462">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f4" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f5"><ix:continuation id="Text_59232552a526469d8af3344cc1ee26462">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="6">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_584e27a0627646aca115ab5178254f07" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4ee7f30dae904ac9b29e30d4ae582e81" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction></ix:nonFraction> percent</span>
            convertible senior notes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_cc24fb43c0744f1c98325749d3d1c0eb" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">622,242</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
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            convertible senior notes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConvertibleDebt" id="Fact_81ca00edf85442d7a959529afc711233" contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">542,314</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_3fc509e3ce564c3bbe4ada075c9f6bf3" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">186,156</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LoansPayableToBank" id="Fact_1a31cb06bce14608b6b4bc53c537a2e8" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">60,054</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilities" id="Fact_4f4ce1cf534445a182bc4dc79c4da3ed" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,295</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OtherLiabilities" id="Fact_14ee837947184542bf24c811e63d710b" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,505</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligations" id="Fact_67f1e8de33db4b3ba71a251d6969a0e4" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,369,195</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligations" id="Fact_0db6c0acf39c4704b8b7fb0682124be0" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,251,050</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_66f728e151b74fe99d367269b42506b7" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,535</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="ions:LongTermObligationsCurrent" id="Fact_6b303576d07b435ebdc0b94cf229a5a7" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,526</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_147209ef0e4d4ccf9a6541966995a76b" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,361,660</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:LongTermObligationsNoncurrent" id="Fact_85488b1118b143d68b8dce7fa49d282e" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,247,524</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f5" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f6">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">106</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>
<div><ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f6" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f7">
<div><br />
  </div>
</ix:continuation>

  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f7" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f8">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt and Call Spread</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f8" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f9">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f9" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f10">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_367e2a67a1be4e9c8bd17911906d63c7" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> Percent
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</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f10" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f11">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f11" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f12">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_2d22395aabdd45428dd1c0e462820b05" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction>
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</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f12" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f13">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f13" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f14"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_599676c995b8459d807f45a7ee7d2f44" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" escape="true" continuedAt="Text_47cde8034434480a923fd5fa8f7a82131">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
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</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f14" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f15"><ix:continuation id="Text_47cde8034434480a923fd5fa8f7a82131" continuedAt="Text_47cde8034434480a923fd5fa8f7a82132">
<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f15" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f16"><ix:continuation id="Text_47cde8034434480a923fd5fa8f7a82132">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


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    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_4e7d0c84148e4e03b9c28d14b2835d31" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_365fed63babc4a6bb8c7f28d097d5fcf" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">632.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_905841f59f744368a1a8831f1229b58f" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_ca0956ae2da341f1b584cfebcf6fbda4">April 2026</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ac6cfb00eadb43ab8dbc9d9b0a66c36b" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction> percent</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_ee7857511bae4b80a0951d97202f10f3" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction> percent</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_ee0d8d54b8404df19d942fdd0dce8cec" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.84</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_64d3b7341c9445cb96a76ae0949cea61" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_032f4e8090c04e37b6ea7f0767ae40fb" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">10.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_dd185d0348874f41b1673a1d53c75cd8" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes by increasing the effective conversion
    price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bfd6b6ef12d54dd69b7bb25e4dc023be" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. We increased our effective conversion price to $<ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_1e99044032054151b68ab7d407ce7341" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">76.39</ix:nonFraction> with the same number of underlying shares as our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_c2541f19c2eb4272b069dbb09040331d" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The call spread cost
    us $<ix:nonFraction name="ions:CallSpread" id="Fact_62280387c71042d190729004344a6d4f" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">46.9</ix:nonFraction> million, of which $<ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_6cde532176644f069d0768d29ee34f5c" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">136.7</ix:nonFraction>
    million was for the note hedge purchase, offset by $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_ed3e7c5441c1428a9f0b9b73200885b2" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">89.8</ix:nonFraction> million we received for selling the warrants. Similar to our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ddc3fd37e7d44019a82c348268c4dcc7" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_bb774b3cfa83474bbd8866c854f9a23b" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The note hedges will expire upon maturity of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b29b1aabd45b45c290d813b0bf76e8a4" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>%
    Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f2e48a9887d24c99a4dc4ff32dc57a99" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes. The holders of the <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_02477ded96b648478cf9a94e2a340f3e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% Notes do not have any rights with respect to the note hedges and warrants.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a81c1aece51b4f0b8c19c1bcb7440532" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction> Percent
    Convertible Senior Notes and Call Spread</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain
    holders of our existing <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fde689883bbb46fa805260842748f20d" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes to exchange $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_1f0edd58b2774e50bf4b1c8a4555dfcd" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">375.6</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_cc6dcd78fcf04e27bc59b7ea7ad75d34" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes for $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_50cb6f6f80c947d1bfdff5d714e46302" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">439.3</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_9f37f248594c430bac51a55afbba8ca0" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes, and to issue $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_dad8a1ae4d1c4fa1921e11974de51029" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">109.5</ix:nonFraction>
    million of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_85d60578550147e0a6311578027faa13" contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f25" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f26"><ix:nonNumeric name="us-gaap:ConvertibleDebtTableTextBlock" id="Text_4c1b65a25fd04140ba02762f4e96676c" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" escape="true" continuedAt="Text_05869894e75b49db8ed7bc079b4f07d51">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
    we had the following <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_5a3580c97a344a8193995ad8eac3f5a4" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: top; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_68012bda03d3466eafeed521f71ea2d2" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentCarryingAmount" id="Fact_3ebbf6d7e4a843548ccfb2e4690a71d2" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">548.8</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_55f5a350ea2d4246b94e3459c056190d" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.3</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_823fe367bb0d42249b87ea8d290aa62a">December 2024</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_77ce30228a504648ab1de2372b883044" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction> percent</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: top; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateEffectivePercentage" id="Fact_38b86a39fb2842d6a81312dccbaddbe1" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.5</ix:nonFraction> percent</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DebtInstrumentConvertibleConversionPrice1" id="Fact_c206e30ca6b74e60bf7326d84b35cafd" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">83.28</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_6cfe644c01ee43fe97a41569dbecd6ca" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DebtInstrumentConvertibleSharesSubjectToConversion" id="Fact_48c4e1d5cd6d4bcb84472d42df72435a" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.6</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_add9814b12a1420392f4e754754c3f5e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which
      was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7c6c6a40bf924b02a94e810787ecc6df" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%
    Notes by increasing the effective conversion price on our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d5f2df0b736f4a5cb82043f0a32c8911" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price to $</span><ix:nonFraction name="ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread" id="Fact_c030555eba6d4c8b89018fa35171b715" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">123.38</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying shares as our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_a06fad74f62f4cce85190746d0159678" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span><ix:nonFraction name="ions:CallSpread" id="Fact_eb1b2b5964d74e02b285e1f179e406cb" contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">52.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of
      which $</span><ix:nonFraction name="us-gaap:PaymentsForHedgeFinancingActivities" id="Fact_a8ef89890b1849959a4e79cddecf2b34" contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase,
      offset by $</span><ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfWarrants" id="Fact_fda60b63b1b64c389d557236420032be" contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">56.1</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the
      warrants. Similar to our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_124d77bb56934d7a9970251719ea367d" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are
      subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2d5b3c670d1144aab03131c0abc16610" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8fd1f36899ac455daca2bb87de1df977" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_11c62c6c5c4a4a88acf4a54c3891b368" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_7438638d57584dfb92975e16d0bb70f8" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_11df1b58ae8844809f1ce3cb7b4b0633" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction> Percent
    Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we repurchased $<ix:nonFraction name="us-gaap:DebtInstrumentRepurchasedFaceAmount" id="Fact_173429ae27c140dcbd0901c416b69acd" contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">247.9</ix:nonFraction>
    million in aggregate principal amount of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_d712328617e84590b7cad8ab33d7d20d" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $<ix:nonFraction name="us-gaap:GainsLossesOnExtinguishmentOfDebt" id="Fact_487566fe6bf14047a56b88d31ba8ac5a" contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.6</ix:nonFraction> million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b7dffcd402124b23933942c2219bdcd6" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_929e5d1b838f4adc965db63b3eb9c93e" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_8a3fa1e156a4466f8ecc35ee505d2c3b" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes with $<ix:nonFraction name="us-gaap:RepaymentsOfConvertibleDebt" id="Fact_9e0d098270c84c5797fa91e125b8551f" contextRef="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">62.0</ix:nonFraction> million of cash at maturity in November 2021.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_ca8ad11ea8114d63bada097b91311cd0" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">0</ix:nonFraction>% and <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_f182b1871b684cf1818024f6e203ac62" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="5" scale="-2" format="ixt:num-dot-decimal">0.125</ix:nonFraction>% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to <ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_d779e40c25674ddf9fd1ba75ff4b61ab" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal"><ix:nonFraction name="ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" id="Fact_5263592fee374a07839e2d8696db42e3" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">100</ix:nonFraction></ix:nonFraction> percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_fc0710aa0f424da783b2a744c9736458" contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction>% Notes were subject to similar terms.</div>
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  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f39" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f40">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f40" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f41">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2022, 2021 and 2020 included $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_7929643c46eb4d899bb5eb0f39b314e4" contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.3</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_9665623f5c3b4275a1389e2903feec32" contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:AmortizationOfFinancingCosts" id="Fact_88c7dc0fce0543bba9a37f924f25ee3b" contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotesMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.2</ix:nonFraction> million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f41" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f42">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f42" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f43">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing Arrangements</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f43" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f44">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f44" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f45">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Operating Facilities</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f45" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f46">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f46" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f47">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_4a0c024b965c4f51b897f9cf5bc80424" contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">79.4</ix:nonFraction> million and our manufacturing facility for $<ix:nonFraction name="us-gaap:PaymentsToAcquireBuildings" id="Fact_06974c574f644e5baacbd3f8e2c599a6" contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">14.0</ix:nonFraction> million. We financed the purchase
    of these <ix:nonFraction name="ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" id="Fact_802514d6121f4f3ca8efa9133eb869cd" contextRef="c20170701to20170731" unitRef="U013" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> facilities with mortgage debt of $<ix:nonFraction name="us-gaap:DebtInstrumentFaceAmount" id="Fact_1c1b0d341f0d4a39b8dd7164eab2e39d" contextRef="c20170731_DebtInstrumentAxis_LongTermMortgageDebtMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">60.4</ix:nonFraction>
    million in total. Our primary R&amp;D facility mortgage had an interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_2e21e0a6347e447a8991607c0227050a" contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">3.88</ix:nonFraction> percent. Our manufacturing facility mortgage has an
    interest rate of <ix:nonFraction name="us-gaap:DebtInstrumentInterestRateStatedPercentage" id="Fact_b8df62c274f14f0499a84c79aa3dd4f9" contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember" unitRef="U003" decimals="4" scale="-2" format="ixt:num-dot-decimal">4.20</ix:nonFraction> percent. During the first <ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_cec9dfdd051e4462bf766547d85be9b4" contextRef="c20220101to20221231_DebtInstrumentAxis_ManufacturingFacilityMortgageMember" format="ixt-sec:durwordsen"><ix:nonNumeric name="ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" id="Fact_885a5330a5d64c1ca25849873c2df457" contextRef="c20220101to20221231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric></ix:nonNumeric> of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August 2027. We repaid
    our primary R&amp;D facility mortgage in October 2022 in conjunction with a sale and leaseback transaction.</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f47" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f48">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f48" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f49">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into <ix:nonFraction name="ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" id="Fact_8733f15524b344938a5622966d91cd3f" contextRef="c20221001to20221031" unitRef="U014" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell,
    subject to meeting certain closing conditions, <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_d19a188162204459bb6a7d2c5b905500" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> lots of undeveloped land adjacent to our headquarters. We sold the facilities at our
    headquarters, which includes our primary R&amp;D facility, for a total purchase price of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_995ff98913014ef6a5f5fc51445c7128" contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">263.4</ix:nonFraction> million and we expect to receive total proceeds
    of $<ix:nonFraction name="us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment" id="Fact_451514a20aac4c9e987035912240b2d5" contextRef="c20230101to20230222_PropertyPlantAndEquipmentByTypeAxis_LandMember_StatementScenarioAxis_ScenarioForecastMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">33.0</ix:nonFraction> million upon the close of the sale of the <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_a8c5588ea2e04cc99ff52c8cb117bb7b" contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction>
    lots. We used a portion of the sale proceeds to extinguish our outstanding mortgage debt on our primary R&amp;D facility of $<ix:nonFraction name="us-gaap:RepaymentsOfSecuredDebt" id="Fact_ee22c79230e54d5289dec6e7979e0722" contextRef="c20221001to20221031_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">51.3</ix:nonFraction> million.</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f49" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f50">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f50" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f51">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Debt Maturity Schedules</div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f51" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f52">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f52" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f53"><ix:nonNumeric name="srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock" id="Text_16539426e6924191b5cc465550dba8af" contextRef="c20220101to20221231" escape="true" continuedAt="Text_70c0eee1e6d3443a8599b0f9fc1068a11">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2022 are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f53" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f54"><ix:continuation id="Text_70c0eee1e6d3443a8599b0f9fc1068a11" continuedAt="Text_70c0eee1e6d3443a8599b0f9fc1068a12">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f54" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f55"><ix:continuation id="Text_70c0eee1e6d3443a8599b0f9fc1068a12">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2023</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" id="Fact_d2eb54062a6d4f188ef1dbae3b8653d3" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,281</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" id="Fact_c42e928b65cd45aa923675e567769ac7" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">550,107</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">595</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" id="Fact_5163088d8dfb4bd8afb6a945c3e15b83" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">633,095</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" id="Fact_04194527fb664e52a3ac79595e34b654" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">447</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" id="Fact_74f3f2a83bb64af5b0b4b21df7d35ef0" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">8,708</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebt" id="Fact_41f58f8c96774a38af7b7c1cc41eabb9" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,194,233</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LongTermDebtCurrent" id="Fact_bc879ac3c37f49de90a976632193e86e" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">151</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:InterestPayableCurrentAndNoncurrent" id="Fact_ef9db53e88e14db9b13d2afa08b9cc23" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,526</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredFinanceCostsNet" id="Fact_97e59891cc4a4a90baf9d56b32982707" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,831</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LongTermDebtNoncurrent" id="Fact_2e8033307b594b4f9b2e30ee6ba95bc3" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,175,725</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


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<div><ix:nonNumeric name="us-gaap:LesseeOperatingLeasesTextBlock" id="Text_816a383efe384026825a397c06709b4a" contextRef="c20220101to20221231" escape="true" continuedAt="Text_493df461273a40babb204c965defc1381">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_f720c6530d1d4a0a9db7c9c5651ae759" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> remaining option to extend the lease for an additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_c08e7408596346fea9c2156de05912d7" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadFacilityMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases. In September 2022, we
    exercised our option to extend <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfLeasesThatWereExtended" id="Fact_cb012423717f470db0c20f0094cc1540" contextRef="c20220901to20220930_PropertyPlantAndEquipmentByTypeAxis_CarlsbadOfficeSpacesMember" unitRef="U016" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> of these leases, extending our term from January 2023 to May 2027. We have <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_fda06318ab41423f9e871d23c3ba6480" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_CarlsbadOfficeSpacesMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> remaining options to extend this lease. Our other office space lease in Carlsbad has an initial term ending in 2023.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Financing Arrangements</span>, we lease our headquarters, which includes our primary R&amp;D facility, as part of a sale and leaseback transaction that closed in October 2022. The initial lease term for our headquarters facilities is <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_7f2058c8172e474bbf205fda14546132" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:duryear">15</ix:nonNumeric> years with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_2ee2e32f70634bcfa6b92ccee44f0bdf" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U017" decimals="0" scale="0" format="ixt:num-dot-decimal">2</ix:nonFraction>
    additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_1488c1954cd849a1a4f6161cf2b82691" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" format="ixt-sec:durwordsen">five years</ix:nonNumeric> each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_a1b244754eec475a945bcce4913ec530" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million. In connection with the sale
    of our <ix:nonFraction name="ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" id="Fact_17aadca36cd14bb7b824374f744e4abc" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember" unitRef="U015" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D
    facility for us on those lots. Once this new facility is completed, our lease will commence.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Oceanside Lease</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside,
    California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space.
    We will lease the facility for an initial term of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_9b1b9a661daa423fbcf3177e16e7acd8" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" format="ixt-sec:durwordsen">20 years and 3 months</ix:nonNumeric> with options to extend the lease for <ix:nonFraction name="ions:LesseeOperatingLeaseNumberOfOptionsToExtendLease" id="Fact_b4ac51899bb74d12bee122785cf15b28" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" unitRef="U017" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> additional terms of <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_cc46548d99c74f729c90f516a7a34297" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" format="ixt-sec:duryear">10</ix:nonNumeric> years each. The lease
    will commence when the lessor&#8217;s construction is complete and we are able to begin constructing tenant improvements.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Boston Leases</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_1cf767bfa2604645b03665b44c8069bb" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durmonth">123</ix:nonNumeric> months and an option to extend the lease for an
    additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_c9d11c93abf3409aab88ca3e2efcb6a1" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric> term. Under the lease agreement, we received a <ix:nonNumeric name="ions:LesseeOperatingLeasePeriodOfFreeRent" id="Fact_ba6fa8c8bcc140258a36c6828c2ab217" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_BostonOfficeSpaceMember" format="ixt-sec:durwordsen">three-month</ix:nonNumeric> free rent period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement
    date was in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending <ix:nonNumeric name="us-gaap:LessorOperatingLeaseTermOfContract" id="Fact_f3673b6f6d8a469cb3fc9b19fe6c9445" contextRef="c20220131_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durmonth">83</ix:nonNumeric> months following the sublease commencement date with no option to extend the sublease. Under the sublease agreement we provided a <ix:nonNumeric name="ions:LessorOperatingLeasePeriodOfFreeRent" id="Fact_bdb3d42dbeaf484494c12e827a769a24" contextRef="c20220101to20220131_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced on January 6, 2022. We will receive lease payments over the sublease term totaling $<ix:nonFraction name="us-gaap:LessorOperatingLeasePaymentsToBeReceived" id="Fact_7c8de04d910848adb798d3e411c0825d" contextRef="c20220131_PropertyPlantAndEquipmentByTypeAxis_SubleasedOfficeSpaceInBostonMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">9.6</ix:nonFraction> million.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in November 2021.
    We are leasing this space under a non-cancelable operating lease with an initial term ending <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseTermOfContract" id="Fact_f252e6bc1ca849dfb22869bd4a71369a" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durmonth">91</ix:nonNumeric> months following the lease commencement date and
    an option to extend the lease for <span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c">an</span> additional <ix:nonNumeric name="us-gaap:LesseeOperatingLeaseRenewalTerm" id="Fact_093b7e88a1474547a8fe7129936aa7cd" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">five-year</ix:nonNumeric>
    term. Under the lease agreement, we received a <ix:nonNumeric name="ions:LesseeOperatingLeasePeriodOfFreeRent" id="Fact_99931a7181e04c71bbd9180a5f64f952" contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" format="ixt-sec:durwordsen">seven-month</ix:nonNumeric> free rent period, which commenced on November 1, 2021. Our lease payments over the
    initial term total $<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_c350c485d2194852998ea1b496903ff5" contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.8</ix:nonFraction> million.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2022</div>
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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseRightOfUseAsset" id="Fact_42b72db309654cf1bdbfe546a3a2176d" contextRef="c20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">181.5</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiability" id="Fact_44caa1523d334df48c7b2561738097e4" contextRef="c20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">186.2</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1" id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7" contextRef="c20221231" format="ixt-sec:duryear">13.8</ix:nonNumeric> years</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent" id="Fact_0f6726aa9c174130a3010b4dad4799ef" contextRef="c20221231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">6.9</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
</ix:continuation></div>

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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">109</div>

    </div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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<div><ix:continuation id="Text_493df461273a40babb204c965defc13828" continuedAt="Text_493df461273a40babb204c965defc13829">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022,
    2021, and 2020 we paid $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_826cead5743b4e90a9d8b807e97fe422" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">4.0</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_297fcce7f2e44b348fe63e7be360cf7c" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.3</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeasePayments" id="Fact_50e928616e964a8c94f28d1e4409995c" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.8</ix:nonFraction> million of lease payments, which were included in operating activities in our consolidated statements of cash flows.</div>
</ix:continuation>

  <ix:continuation id="Text_493df461273a40babb204c965defc13829" continuedAt="Text_493df461273a40babb204c965defc13830">
<div><br />
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</ix:continuation>
  <ix:continuation id="Text_493df461273a40babb204c965defc13830" continuedAt="Text_493df461273a40babb204c965defc13831"><ix:nonNumeric name="us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock" id="Text_4ac550fe12b346a487d1639e48d94f8d" contextRef="c20220101to20221231" escape="true" continuedAt="Text_97968a5cefee4ce19ff16cca20752a4e1">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, the future payments for our operating lease liabilities are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_493df461273a40babb204c965defc13832" continuedAt="Text_493df461273a40babb204c965defc13833"><ix:continuation id="Text_97968a5cefee4ce19ff16cca20752a4e2">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" id="Fact_9240bc8118ea402f85a2119c7486d19d" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,071</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" id="Fact_4609f99ef9604c9aae3baed51a3c3fed" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,391</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree" id="Fact_d11239309f5945a3891ef526d1491daa" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,640</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFour" id="Fact_43a6c7550e004272b7f9ca99a8ba22d8" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,781</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearFive" id="Fact_74899d789ebf4c2ebccd545b74c63e21" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">20,800</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" id="Fact_3931369a624044a9b1905cb93b92544f" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">196,911</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue" id="Fact_3603a725690b46dda9be3db4e21043c4" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">299,594</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%;">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" id="Fact_6d8e7a3e7ccb4ac9a37ea341d9cadf8c" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">113,438</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:OperatingLeaseLiabilityCurrent" id="Fact_599739bca7c14726b6810c3c3a59fcff" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,215</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 88%; padding-bottom: 4px;">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingLeaseLiabilityNoncurrent" id="Fact_5bc4a22d2bca49aca884201dc1170194" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">178,941</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_493df461273a40babb204c965defc13833" continuedAt="Text_493df461273a40babb204c965defc13834">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_493df461273a40babb204c965defc13834">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_b625c294a3bd434f8c74620b51e1ea20" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.3</ix:nonFraction> million,
    $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_37e7125f4da2437a81d1b7f1853e4554" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.4</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLeaseExpense" id="Fact_a6f37ce5e1654e67b6bfb04f2bfaa94b" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.7</ix:nonFraction> million for the
    years ended December 31, 2022, 2021
    and 2020, respectively. </div>
</ix:continuation></div>

  <div><br />
  </div>

  <div>
    <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f56" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f57">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Royalty Revenue Monetization</div>
</ix:continuation>
  </div>

  <div>
    <ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f57" continuedAt="Text_2718a095d2c64c9e840107ece8b3226f58">
<div><br />
    </div>
</ix:continuation>
  </div>

  <div><ix:continuation id="Text_2718a095d2c64c9e840107ece8b3226f58">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontRoyaltyPaymentReceived" id="Fact_c8ba625af5db4c629715e10efedcdff1" contextRef="c20230101to20230131_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">500</ix:nonFraction> million and we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableForAdditionalMilestones" id="Fact_d5508d985dec4c9299c67fd453890fd5" contextRef="c20230131_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million in additional milestone
    payments. Under the terms of the agreement, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_04d45df1075f4c7282dba5c75f87090a" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of our SPINRAZA royalty payments from 2023 through 2027,
    increasing to <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_7db57813067c495a9024650b8968a999" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">45</ix:nonFraction> percent of royalty payments in 2028, on up to $<ix:nonFraction name="ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" id="Fact_9f09740d482b4450bde402e99f9264a9" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction> billion in annual sales. In addition, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_4f14fcd874cc407499d3f48e153e6244" contextRef="c20230131_ProductOrServiceAxis_PelacarsenMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of
    any future royalty payments on pelacarsen, our medicine in development for lipoprotein(a), or Lp(a), driven cardiovascular disease. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma
    reach either $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_2203af9e770d4ee987086d61868bd2ee" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction> million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_dcfdc1338630420c9019168b9412101d" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction>
    million, depending on the timing and occurrence of FDA approval of pelacarsen. We will begin accounting for the royalty monetization agreement in the first quarter of 2023.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are authorized to issue up to <ix:nonFraction name="us-gaap:PreferredStockSharesAuthorized" id="Fact_cdf2c784100f453c85b910f7ffa74a1e" contextRef="c20221231_StatementClassOfStockAxis_PreferredStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction>
    million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2022, there were <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_9e3c83d35b1a4ad9bb5804db20a70950" contextRef="c20221231_StatementClassOfStockAxis_PreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction> shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have <ix:nonFraction name="us-gaap:PreferredStockSharesOutstanding" id="Fact_56071bcb2d56480397a630e97def5c32" contextRef="c20221231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:PreferredStockSharesIssued" id="Fact_5fe1b66991274e8cbc8b7286eae05354" contextRef="c20221231_StatementClassOfStockAxis_SeriesCPreferredStockMember" unitRef="U002" decimals="INF" scale="0" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction> issued or outstanding shares as of December 31, 2022.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022 and 2021, we had <ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_292edcba897f40209ed42c14feed0f2e" contextRef="c20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesAuthorized" id="Fact_10c668f50b664401a30c1bb6a51edb5a" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-6" scale="6" format="ixt:num-dot-decimal">300</ix:nonFraction></ix:nonFraction> million shares of common
    stock authorized, of which <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_6d69412111c94f649e3bc6185a645456" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_5f23b4a620974ffa9ac1338867c08a09" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">142.1</ix:nonFraction></ix:nonFraction> million and <ix:nonFraction name="us-gaap:CommonStockSharesOutstanding" id="Fact_eba69077d17e4204b64b00ee384f8ab0" contextRef="c20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal"><ix:nonFraction name="us-gaap:CommonStockSharesIssued" id="Fact_7461dbbf5e58485bbd613618075e0ee5" contextRef="c20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">141.2</ix:nonFraction></ix:nonFraction> million were issued and outstanding, respectively. As of December 31, 2022,
    total common shares reserved for future issuance were <ix:nonFraction name="us-gaap:CommonStockCapitalSharesReservedForFutureIssuance" id="Fact_47e88bfdb1664c48a2b1ff64f80389f5" contextRef="c20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">43.2</ix:nonFraction> million.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022,
    2021 and 2020, we issued <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_0ee4b00a77834001bc604428d95159c5" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction> million, <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_6d8eb059ce834187b603ca07d5abb207" contextRef="c20210101to20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.1</ix:nonFraction> million and <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesShareBasedCompensationGross" id="Fact_edd10ce23a74492e8176afb94a7abdb0" contextRef="c20200101to20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.7</ix:nonFraction> million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_d6943984a2cd41b0a8cb3b1deb1f9fc2" contextRef="c20220101to20221231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.4</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_5fbad294b6304ae4a8a72a7d07384a09" contextRef="c20210101to20211231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.6</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions" id="Fact_4af5fbc849034e59b7d2901adc45af29" contextRef="c20200101to20201231_StatementClassOfStockAxis_CommonStockMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">52.0</ix:nonFraction> million in 2022,
    2021 and 2020, respectively.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved a share repurchase program of up to $<ix:nonFraction name="us-gaap:StockRepurchaseProgramAuthorizedAmount1" id="Fact_44310671d1664bfca3445b963a157027" contextRef="c20190930" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">125</ix:nonFraction> million of our common stock. In 2019, we repurchased <ix:nonFraction name="us-gaap:StockRepurchasedDuringPeriodShares" id="Fact_a0ec8c80989241c28567434e9da68f95" contextRef="c20190101to20191231" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">535,000</ix:nonFraction> shares for $<ix:nonFraction name="us-gaap:PaymentsForRepurchaseOfCommonStock" id="Fact_b3c70b4e95ca4205b78bd5e2e50aeeab" contextRef="c20190101to20191231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">34.4</ix:nonFraction> million. In the first quarter of 2020, we repurchased an additional <ix:nonFraction name="us-gaap:StockRepurchasedDuringPeriodShares" id="Fact_e459a3912815439c8077106b57fb5880" contextRef="c20200101to20200331" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.5</ix:nonFraction> million shares for $<ix:nonFraction name="us-gaap:PaymentsForRepurchaseOfCommonStock" id="Fact_2b769cf5ebe543ef91ba7139fec3a4d2" contextRef="c20200101to20200331" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">90.5</ix:nonFraction> million.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1989 Stock Option Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides
    for the issuance of non-qualified and incentive stock options for the purchase of up to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_2a82263b39a7474ba2b3298ff2f3a349" contextRef="c20221231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">20.0</ix:nonFraction> million shares of common stock to our employees,
    directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the
    repricing. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_300b6e73bf984f4ba7b411e09fd8ac0a" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_f9de77fe0ed4406e89bc6cca403c951f" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction>percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_8c42e3e31eb04afc9a1a6d089d774313" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant and the
    balance vesting ratably, on a monthly basis, thereafter and have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7077ae6833184dee85f5278742d25b56" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_StockOptionPlan1989Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. At December 31, 2022, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_add8de5b32ae49bb87473e4eddedffb6" contextRef="c20221231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction> thousand options were outstanding, of which
    options to purchase <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_803cbfb1dea74d34930f47cade7a9b19" contextRef="c20221231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">12</ix:nonFraction> thousand shares were exercisable, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_8c931ba74e0d4e5c8d57ed4b294c4a22" contextRef="c20221231_PlanNameAxis_StockOptionPlan1989Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">65</ix:nonFraction> thousand shares were available for future grant under the 1989 Plan.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the
    issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from
    our stockholders, we amended our 2011 Equity Incentive Plan, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2011 Plan,</span> to increase the total number of shares reserved for issuance. We increased the shares
    available under our 2011 Equity Incentive Plan from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_5882aa832aa646c6b635e3bfe41d5f81" contextRef="c20150531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.5</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_1f00ba80dcbf4591a6c03449d0ff3e6e" contextRef="c20150630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million in June 2015, from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_b4182e47d22e4ab1b6c25c3beae739b7" contextRef="c20150630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">11.0</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_73b32b7412144ae2844353056c2328ce" contextRef="c20170531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">16.0</ix:nonFraction> million in May 2017 and from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_67f1d774e8d34fbbbdcb82cbb830d91a" contextRef="c20170531_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">16.0</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_dd1127c8a7ec4eedb63afb7ca6169e93" contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.0</ix:nonFraction> million in June 2019. In the second quarter of 2021, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_57cfec8e7dd44452863fefb2e13edfc5" contextRef="c20190630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">23.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_de84fcdda0694d5aa3e5b25edbac3ff6" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">29.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and added a fungible share counting ratio whereby the share reserve will be reduced by </span><ix:nonFraction name="ions:IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" id="Fact_23f42a38660942f6be12a03f919b693c" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="1" sign="-" scale="0" format="ixt:num-dot-decimal">1.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and increased by
    </span><ix:nonFraction name="ions:IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" id="Fact_4de4ba08df4c4468acb8a87fe4bb1be6" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="1" scale="0" format="ixt:num-dot-decimal">1.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock returning from a
      full value award. </span>The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights
    that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only stock options, RSU
    and PRSU awards to our employees, directors and consultants. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_763f3de6711b427ba6c4d7792811777d" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_13d5cd5cb0eb4f0e964e186051bcf7a9" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_3a3d9b453a064adea83801f87842c09c" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant
    and the balance vesting ratably, on a monthly basis, thereafter and have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_7cc41a014493404ba087ca86ab407ebe" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. Options granted after December 31, 2021 have a
    term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_c3a19253882c43ce8572c4be5c36bb38" contextRef="c20220101to20221231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric>. We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_323dc3ca223441ed8cae26677d80920d" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2022, a
    total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_f6eb4ef69d9549b79f43b5ca7f3d3f65" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">13.7</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_c37dd0f781d649a5bc97d2c87bbaeacf" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">9.4</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_f19dff70c85e4b53ab5b44f7e4b872f2" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.7</ix:nonFraction> million restricted stock unit awards were
    outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_f121d278af9942b4ba6d23912dbef6db" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.8</ix:nonFraction> million shares were available for future grant under the 2011 Plan.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If <ix:nonFraction name="ions:NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_8f959a059fb340fc9f6dfdc4cbdfc6d9" contextRef="c20220101to20221231_PlanNameAxis_EquityIncentivePlan2011Member" unitRef="U018" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins <ix:nonNumeric name="ions:PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_5cf8f8a57af249d4a6cce115597f8861" contextRef="c20220101to20221231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">three months</ix:nonNumeric> before and ends <ix:nonNumeric name="ions:PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" id="Fact_4b4db5c64d7f42eca6f341535cd62db4" contextRef="c20220101to20221231_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">twelve months</ix:nonNumeric> following a change in control of the company, the impacted employee&#8217;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the termination date.</div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2020 Equity Incentive Plan</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In connection with the Akcea Merger in October 2020, we
      assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020
      Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_c2fdd0b5f17c4a559deafa59528e79eb" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment
      to the 2020 Plan. The amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_b0e9739857ca4a9ca5aef49a60ac50e3" contextRef="c20201231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_c1bebf52134d402a8958171cfbc5c265" contextRef="c20210630_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We assumed the 2020 Plan in connection with Ionis&#8217; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_f1c93af494b04abea846be47da9b6f21" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period, with <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" id="Fact_bf4c2072cc4b4282835c60cb240d0d17" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent exercisable at the end of <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1" id="Fact_6ad6746c60684d1cade6e5856104044e" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member_VestingAxis_ShareBasedCompensationAwardTrancheOneMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric> from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_83e080be39814e6ba0c957ebe364dd77" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">seven years</ix:nonNumeric>. Options granted after December 31, 2021 have a term of <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_8c17823f65d24056a081b6cf50f1e55f" contextRef="c20220101to20221231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_StockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric>.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a <ix:nonNumeric name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1" id="Fact_3568607a84604758a037e6132fdacf7c" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen">four-year</ix:nonNumeric> period. At December 31, 2022, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_7b23f3391b8648699d7f9d9bdfc98ad2" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million
    options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_ad09798ba381488da5e4c73d17fddca5" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">61</ix:nonFraction> thousand were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_998c6813ad25478d8df2ef4e673ad903" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_445e0eb67023409bac8ed8d6e705c2d6" contextRef="c20221231_PlanNameAxis_EquityIncentivePlan2020Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction> million shares were
    available for future grant under the 2020 Plan.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Corporate Transactions and Change in Control under 2011 and 2020 Plans</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and</div>
        </td>

  </tr>


</table>
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992
    Non-Employee Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or
    the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_0e9dea3a9bb44f258d4a6a1eeffbb1b0" contextRef="c20150531_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.2</ix:nonFraction> million to <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_e55c20e37dc6464eb74bde99a3d220dc" contextRef="c20150630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction> million. In June 2020, after receiving approval from our
    stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>
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<div><br />
  </div>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">An increase to the total number of shares reserved for issuance under the plan from </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_fda3670487384cb49c8eb41d6d8f4665" contextRef="c20150630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_8b16c9fcbd8a4de6a3ff40e97438a3a8" contextRef="c20200630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares;</span></div>
        </td>

  </tr>


</table>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div>
        </td>

  </tr>


</table>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A revision to the vesting schedule of new awards granted; and</div>
        </td>

  </tr>


</table>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An extension of the term of the plan.</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Options under this plan expire <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_e6b00753880241348e596a82fa22bab2" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" format="ixt-sec:durwordsen">10 years</ix:nonNumeric>
    from the date of grant. At December 31, 2022, a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_28beff5bd3d14e0c9936c3a0e4bfd184" contextRef="c20221231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.9</ix:nonFraction> million options were outstanding, of which <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_5c3c554e640546a481c2968b37014870" contextRef="c20221231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million were exercisable, <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber" id="Fact_d025b834777346cfa313dfb503dafd03" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction> million restricted stock unit awards were outstanding, and <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" id="Fact_03da27efb55141628520731fb9e70ab8" contextRef="c20221231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.6</ix:nonFraction>
    million shares were available for future grant under the 2002 Plan.</div>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>
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<div><br />
  </div>
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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Purchase Plan</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_3b40f4cda8e040fdba6be624573711c9" contextRef="c20090601to20090630_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">150,000</ix:nonFraction> shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized" id="Fact_627f300828104f14b873bf05eda50f67" contextRef="c20220101to20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="0" scale="0" format="ixt:num-dot-decimal">150,000</ix:nonFraction> shares of common stock for the ESPP resulting in a total of <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized" id="Fact_e19efe7ddb5143df982e961a832ee9c5" contextRef="c20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.2</ix:nonFraction> million shares authorized under the plan as of December 31, 2022. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed <ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate" id="Fact_ad7d5d970b7445cb891d0cfb579417b5" contextRef="c20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">10</ix:nonFraction>percent of each employee&#8217;s compensation)
    at the lower of <ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" id="Fact_f1124fb149ea4ba28036505d69fad8f3" contextRef="c20220101to20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">85</ix:nonFraction>percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended
    and restated ESPP, employees must hold the stock they purchase for a minimum of <ix:nonNumeric name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" id="Fact_f085e44a32534bbd8486ce10fc828657" contextRef="c20220101to20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" format="ixt-sec:durwordsen">six months</ix:nonNumeric> from the date of purchase. During 2022, employees purchased and we issued to employees <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" id="Fact_36267c2abcb644b69eb45aceda22f69b" contextRef="c20220101to20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.1</ix:nonFraction>
    million shares under the ESPP at a weighted average price of $<ix:nonFraction name="ions:EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" id="Fact_2c284719dc094a59851d962ad33aacae" contextRef="c20220101to20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">28.57</ix:nonFraction> per share. At December 31, 2022, there were <ix:nonFraction name="ions:EmployeeStockPurchasePlanSharesAvailableForPurchase" id="Fact_9bcf03b844ab41c1a8fbd64333e01f0e" contextRef="c20221231_PlanNameAxis_EmployeeStockPurchasePlanMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction> million shares available for purchase under the
    ESPP.</div>
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<div><br />
  </div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Option Activity</div>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb764" continuedAt="Text_1d80c2996fad43938041ca257c446cb765"><ix:nonNumeric name="us-gaap:ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock" id="Text_b08686db7e214f558296c6c15bcdf2af" contextRef="c20220101to20221231" escape="true" continuedAt="Text_53f877dbaddc409894a6ff2ed3f38d501">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2022 (in thousands, except per share and contractual life data):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
</ix:continuation></ix:continuation>
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<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Price Per Share</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Term</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Years)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Aggregate</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intrinsic</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2021</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" id="Fact_c363e628c500466b86c02f00df87e45d" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,864</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" id="Fact_147bf3d775c544d39301adb1493fa05e" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">34.78</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesStockOptionsExercised" id="Fact_65fe49e661654c6fadd66c3158cb37e5" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">123</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice" id="Fact_645eac997a48446a8364fedf6f9b00a2" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">29.35</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" id="Fact_d7093d8852d44af280644f5b3f4724f8" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,860</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" id="Fact_b2d99eaaf66c4310b3826984e917430d" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.96</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2022</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" id="Fact_ac7cb8c9588948168b54c219f469e752" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">14,970</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" id="Fact_3a779dec16434ab39ded18c995252583" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">50.57</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" id="Fact_8a97634ee0de48ab9bba7815890a31ce" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">4.01</ix:nonNumeric></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue" id="Fact_c25c76c1a9f94691b856964b458fadef" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">12,243</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 52%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2022</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" id="Fact_f87605af70314ee88af627c71f1097ba" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,285</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" id="Fact_385eca89102d4e9587c5000cc39964b4" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">53.74</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" id="Fact_7314f310e53045fd9d6e985a8a4eb55d" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">2.56</ix:nonNumeric></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1" id="Fact_bb850db7a9184d57b61549c6a8eeacca" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,651</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb768" continuedAt="Text_1d80c2996fad43938041ca257c446cb769">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The weighted-average estimated fair values of options granted were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_bd436c790ccc47e68cd7e2153d0e63dd" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">18.66</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_4dd2a593ab554175bbb0a93d55390a88" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">24.35</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_a3befa246b7c4d03aced2b483085120f" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">29.43</ix:nonFraction> for the years ended December 31, 2022, 2021 and 2020, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2022, 2021 and 2020 were $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_1218d40eea68418bb4f00f1ad78f4cff" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.4</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_bde2c92764604d8497b0668d13fb888b" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue" id="Fact_8cc0e16daa8e4b2382fc554cc98ddf99" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">15.5</ix:nonFraction> million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_83423df31a3f436fab220d64f20b3ada" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">3.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_9199ba163c904e0aaa3d539cccdda650" contextRef="c20210101to20211231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">8.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:ProceedsFromStockOptionsExercised" id="Fact_6cc972e2025849d8a6820145ab793c87" contextRef="c20200101to20201231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">43.7</ix:nonFraction> million for the years ended December 31, 2022, 2021 and 2020, respectively. For the year
    ended December 31, 2022, the weighted-average fair value of options exercised was $<ix:nonFraction name="ions:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" id="Fact_2b17593a26f3421991429bedce8b1c41" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">40.71</ix:nonFraction>. As of December 31, 2022, total unrecognized compensation cost related to
    non-vested stock options was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" id="Fact_72c37b7b47114b45a9abf8d6722faa52" contextRef="c20221231_AwardTypeAxis_StockOptionMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">41.1</ix:nonFraction> million. We expect to recognize this cost over a weighted average period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_b3913cf410e541fe90a6f1003271ba18" contextRef="c20220101to20221231_AwardTypeAxis_StockOptionMember" format="ixt-sec:duryear">1.1</ix:nonNumeric> years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>
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<div><br />
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Restricted Stock Unit Activity</div>
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>
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<div><br />
  </div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod" id="Fact_32f1bead9c704269b614ad1cd037ad04" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">958</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue" id="Fact_df38f96941f0458f9ca876b79bbed1b6" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.05</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod" id="Fact_22694e1383774415bf4c78c2ec3ee1f6" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">295</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue" id="Fact_d3684b8ecd434d79a0c627293baaf219" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">48.61</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber" id="Fact_28559434ff5b402683a66fe056752875" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,766</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_5d0497b5899240c48adeef1f11e34ed4" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">48.30</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
    2021 and 2020, the
    weighted-average grant date fair value of RSUs granted was $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_6c1a06db93094900a762b6eb164c546f" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2">36.14</ix:nonFraction>, $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_43f43b5a78cc4be1918b46bdde39a8d8" contextRef="c20210101to20211231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">57.02</ix:nonFraction> and $<ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" id="Fact_57cca4b8f1044664988a96c292d978d1" contextRef="c20200101to20201231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">60.57</ix:nonFraction> per RSU, respectively. As of December 31, 2022, total unrecognized compensation cost related to RSUs was $<ix:nonFraction name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" id="Fact_87ca3f2ec59f473aaf7df5ff01d27232" contextRef="c20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">45.8</ix:nonFraction> million. We expect to recognize this cost over a weighted average period of <ix:nonNumeric name="us-gaap:EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" id="Fact_18e1a1c706d54df78d64da3820fb50b9" contextRef="c20220101to20221231_AwardTypeAxis_RestrictedStockUnitsRSUMember" format="ixt-sec:duryear">1.2</ix:nonNumeric>
    years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">113</div>

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<div><br />
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Restricted Stock Unit Activity</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue" id="Fact_8d1f45fc49f745769240429abaa6978d" contextRef="c20221231_AwardTypeAxis_PerformanceSharesMember" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">52.59</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
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  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb786" continuedAt="Text_1d80c2996fad43938041ca257c446cb787">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense and Valuation Information</div>
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_e2891cabb204471380d6c8707ca7c311" contextRef="c20210101to20211231_IncomeStatementLocationAxis_SellingGeneralAndAdministrativeExpensesMember" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">32,700</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:AllocatedShareBasedCompensationExpense" id="Fact_e526ced9a8ee48df88cdbb0fe414de86" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">100,264</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb791" continuedAt="Text_1d80c2996fad43938041ca257c446cb792">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb792" continuedAt="Text_1d80c2996fad43938041ca257c446cb793">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, as part of the Akcea Merger, Akcea&#8217;s outstanding equity awards vested under Akcea&#8217;s Plan. As a result, in 2020, we
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</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb793" continuedAt="Text_1d80c2996fad43938041ca257c446cb794">
<div><br />
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</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb794" continuedAt="Text_1d80c2996fad43938041ca257c446cb795">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization
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</ix:continuation>
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<div><br />
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</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
    2021 and 2020, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</div>
</ix:continuation>
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<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>
</ix:nonNumeric></ix:continuation>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" id="Fact_bdcda0ba9a7942588e74e26d29bbb33b" contextRef="c20220101to20221231_AwardTypeAxis_BoardOfDirectorStockOptionMember" format="ixt-sec:duryear">7.4</ix:nonNumeric> years</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>
</ix:nonNumeric></ix:continuation>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk-Free Interest Rate.</span> We base
    the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Dividend Yield.</span> We base the
    dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb7114" continuedAt="Text_1d80c2996fad43938041ca257c446cb7115">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> We use an average of
    the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb7116" continuedAt="Text_1d80c2996fad43938041ca257c446cb7117">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Expected Life. </span>The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from <span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"><span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad">seven</span></span> to <ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_ca599c0bec514341bfbc694c29062946" contextRef="c20220101to20221231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_EmployeeStockOptionMember_PlanNameAxis_EquityIncentivePlan2020Member" format="ixt-sec:durwordsen"><ix:nonNumeric name="us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" id="Fact_c4148e9887894ea9af96e0d8258b9049" contextRef="c20220101to20221231_AwardDateAxis_IssuedAfterDecember312021Member_AwardTypeAxis_EmployeeStockOptionMember_PlanNameAxis_EquityIncentivePlan2011Member" format="ixt-sec:durwordsen">ten years</ix:nonNumeric></ix:nonNumeric> for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended December 31, 2022. Under the simplified method, we calculate the
    expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_1d80c2996fad43938041ca257c446cb7118">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Forfeitures.</span> We reduce stock-based
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</ix:continuation></div>

  <div><br />
  </div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Income Taxes</div>
</ix:nonNumeric>

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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes is comprised of (in thousands):</div>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_1154d9477ea5403c89bcaba61b591e79" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">258,493</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_74d3abad4f744e0aa68801acc3a6ed6b" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">29,966</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic" id="Fact_8977ca2c8272434794efd8259c5f22b7" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">137,222</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_8425f2adaf6948cdb4db61cdf7def1fc" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">818</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign" id="Fact_15eeca6092a14a5c9b839eb716ea8ae4" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">2,670</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_317564d38d3f4684aaa47f65a5d386e8" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">257,985</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_9fd05fd89e164623ad7d51c758cf30c6" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">29,148</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest" id="Fact_225bd758b4d047a9b56b2a1266e8768e" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">134,552</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="10">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentFederalTaxExpenseBenefit" id="Fact_f7d1c022ad9f48ddaa94094db5e10a09" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">10,522</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CurrentFederalTaxExpenseBenefit" id="Fact_7390edee7ebc486d8f38622d5c52bcc1" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">837</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_ca5d84cba52a406991333d46438a92be" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">86</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_7ac2061535c24653b193dc9c25179163" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">339</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentForeignTaxExpenseBenefit" id="Fact_94c31631758a4c52bc819107405e16bf" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">518</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_273269185dee42eb91195045f6449fc7" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_33a16e765b9c499ba27c595254ef3547" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">551</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CurrentIncomeTaxExpenseBenefit" id="Fact_2d44830595d442f082fda176f5b4c723" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,463</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFederalIncomeTaxExpenseBenefit" id="Fact_87cec1e54272412b8aa84293213da2a9" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFederalIncomeTaxExpenseBenefit" id="Fact_3fdf75baf2f34ebb8e8ae479ea28b0dc" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredFederalIncomeTaxExpenseBenefit" id="Fact_c00a5eec073e447cab0567a91678c321" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">341,728</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_e78064ae2d4443f18407baa35f73bf2f" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_989cd3ae4b8346399913987c81866608" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredStateAndLocalIncomeTaxExpenseBenefit" id="Fact_d254df8f11b14f8594ca47e6a7f95134" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred income tax benefit</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_be2ed18e2072458bba8c88d0a45981b5" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_499db25413694d1996ce63465160cf19" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredIncomeTaxExpenseBenefit" id="Fact_b02665644bb848b5b79ed1b9b7aba937" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">341,728</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_39aa3556afa54b90a94840a97eb5b995" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_d3a17d5cbd604f2eaffbec171dab238a" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">551</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a8769" continuedAt="Text_673aed53fddd435ca232fe29a156a87610">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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<div><ix:continuation id="Text_673aed53fddd435ca232fe29a156a87610" continuedAt="Text_673aed53fddd435ca232fe29a156a87611"><ix:nonNumeric name="us-gaap:ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock" id="Text_51a6178b5d104096a200807a70958787" contextRef="c20220101to20221231" escape="true" continuedAt="Text_268c63ab1a36431fbcb7314655295f3a1">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The
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  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a87612" continuedAt="Text_673aed53fddd435ca232fe29a156a87613"><ix:continuation id="Text_268c63ab1a36431fbcb7314655295f3a2">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; background-color: #CCEEFF;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Statutory rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate" id="Fact_a4b904e0d10e47ab8481b786c1abe1ef" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">6,121</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate" id="Fact_a77137cc5cdc428e9742bd1fec8ff6f2" contextRef="c20210101to20211231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">21.0</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State income tax net of federal benefit</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Loss on debt transactions</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax credits</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other non-deductible items</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
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        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Impacts from Akcea Merger</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent" id="Fact_b6d352deeba44aa781e42a148e18d01c" contextRef="c20210101to20211231" unitRef="U003" decimals="3" scale="-2" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_579c7a65442043da929eea96c26a5f30" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">364</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_d4daf54210844f62bbb1a04059ef74aa" contextRef="c20220101to20221231" unitRef="U003" decimals="3" sign="-" scale="-2" format="ixt:num-dot-decimal">0.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_a992f73d15204a0081e6aa41357a8de5" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,503</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4c434cf931ee4c45825ee90aa9c5caf0" contextRef="c20210101to20211231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">5.1</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxReconciliationOtherAdjustments" id="Fact_bc52c68679ef48cab49f85908463be0f" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">1,391</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EffectiveIncomeTaxRateReconciliationOtherAdjustments" id="Fact_4d88b363955f43e1a07814eb57337204" contextRef="c20200101to20201231" unitRef="U003" decimals="3" scale="-2" format="ixt:num-dot-decimal">0.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 28%; padding-bottom: 4px;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_deca3f5e839941f4a90d3b8031b558aa" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">11,737</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_9706d35248bb454c8a3a3c80240bc33f" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" sign="-" format="ixt:num-dot-decimal">551</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:IncomeTaxExpenseBenefit" id="Fact_05f18d362e2441e2a636fa371d9e87f0" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">345,191</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" colspan="1">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a87613" continuedAt="Text_673aed53fddd435ca232fe29a156a87614">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
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</ix:continuation>
  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a87614" continuedAt="Text_673aed53fddd435ca232fe29a156a87615">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
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</ix:continuation>
  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a87615" continuedAt="Text_673aed53fddd435ca232fe29a156a87616">
<div><br />
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2022 and 2021 are as follows (in thousands):</div>
</ix:nonNumeric></ix:continuation>
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<div><br />
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom;" colspan="2">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost" id="Fact_cf4d0af63f314ebebc4008a2387ff7ba" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">86,983</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_1eb4e0ee7798484c84a06c938cd4969a" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">104,649</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGoodwillAndIntangibleAssets" id="Fact_5dbb3a06f1ce4e86bcf8b0b23175d4c6" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">92,542</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsFinancingArrangements" id="Fact_d5e56b516fd44b23a7d77df2c87dd193" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">34,384</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsFinancingArrangements" id="Fact_56e973c6c9d8438697c10963c3e2b910" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,681</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense limitation</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsInterestExpenseLimitation" id="Fact_c83b54345a1c4b8780d8a7e7358c64bd" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsInterestExpenseLimitation" id="Fact_c3b08cb12f234f2481debf0a48e48ad6" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">6,996</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_7552c538820b415fa183b42f515e84f9" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">119,635</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" id="Fact_454847e0096740a1b60db473f3a38457" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLeasingArrangements" id="Fact_f1bc5ca109b2461198124e062adb4830" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">45,612</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLeasingArrangements" id="Fact_21b8f2ff8dfe4306a563b7b9403bb6ad" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">5,119</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_68255c3bd980428f8ac1596cf0f40278" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">15,813</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsOther" id="Fact_8fd4dba767ea4fb1ad2e077d22dd1144" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">9,929</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGross" id="Fact_db490d6be6234997ab204f135fae4219" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">858,014</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsGross" id="Fact_0e07da67ce43444f913fc9c18171c638" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">706,346</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesPropertyPlantAndEquipment" id="Fact_e25b4841ea8643daaead657546cec52e" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,475</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesPropertyPlantAndEquipment" id="Fact_9878485dcb08467684a2d157588eeafd" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">3,303</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesLeasingArrangements" id="Fact_0d69436048d84a5eb26b450649e27a54" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">44,504</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesLeasingArrangements" id="Fact_f621ee4c764a4d53b8a656ccc5cb49f9" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">4,159</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b5703c2c4764515a3e8ad2afeea59cf" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">313</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxLiabilitiesOther" id="Fact_1b2f279a0c764ac6861cf53127c15459" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,111</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_2aed2e8242ea4d2a953befcd5fd869ee" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">808,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="ions:DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" id="Fact_079ce9450c7a4660ba7391c5cb7a50dc" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">697,773</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_972868dc5873412980ceca72fd836c11" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">808,722</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:DeferredTaxAssetsValuationAllowance" id="Fact_2c9b12b4481545a7ba60367cdb421919" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">697,773</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_57658da53796431d95347a5ae91df615" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:DeferredTaxAssetsLiabilitiesNet" id="Fact_b0ad9b5a1bcf4171839877e1f6c48962" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
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<div><br />
  </div>
</ix:continuation></ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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<div><ix:continuation id="Text_673aed53fddd435ca232fe29a156a87620" continuedAt="Text_673aed53fddd435ca232fe29a156a87621">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate our deferred tax assets regularly to determine whether adjustments to the valuation allowance are appropriate due to changes in facts or
    circumstances, such as changes in expected future pre-tax earnings, tax law, interactions with taxing authorities and developments in case law. In making this evaluation, we rely on our recent history of pre-tax earnings. Our material assumptions are
    our forecasts of future pre-tax earnings and the nature and timing of future deductions and income represented by the deferred tax assets and liabilities, all of which involve the exercise of significant judgment. Although we believe our estimates are
    reasonable, we are required to use significant judgment in determining the appropriate amount of valuation allowance recorded against our deferred tax assets.</div>
</ix:continuation>

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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our valuation allowance increased by $<ix:nonFraction name="us-gaap:ValuationAllowancesAndReservesPeriodIncreaseDecrease" id="Fact_66c86cbe348d4776a343b6ddac2f20fe" contextRef="c20220101to20221231" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">111</ix:nonFraction>
    million from December 31, 2021 to December 31, 2022.
    The increase was primarily related to increases in our deferred tax asset for capitalized research and development expenses.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022, we had
    federal and state, primarily California, tax net operating loss carryforwards of $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_d9f8be4484bf4eb29dfdbd375c201523" contextRef="c20221231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">242.8</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:OperatingLossCarryforwards" id="Fact_ad3cae48e06445f7aefbd80a218590f4" contextRef="c20221231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">461.3</ix:nonFraction> million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2022, we also had federal and California research and development tax credit carryforwards of $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_895e697c597d405a96e760deb75e2c01" contextRef="c20221231_IncomeTaxAuthorityNameAxis_InternalRevenueServiceIRSMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">224.9</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:TaxCreditCarryforwardAmount" id="Fact_8191e961253a4f2faaff06f7920ca14f" contextRef="c20221231_IncomeTaxAuthorityNameAxis_CaliforniaFranchiseTaxBoardMember_TaxCreditCarryforwardAxis_ResearchMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">110.7</ix:nonFraction> million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2035. Our California research and development tax credit carryforwards are available indefinitely.</div>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.</div>
</ix:continuation>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in
      thousands):</span></div>
</ix:nonNumeric></ix:continuation>
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<div><br />
  </div>
</ix:continuation></ix:continuation>
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  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_6f5ba375963f47a19fbb04fed7232165" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,085</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_0f12ba3f88584d21bf0b87b613d47847" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">54,163</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_67e334d942db4ea29c0cbe3ffcea2715" contextRef="c20191231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">69,784</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_3f06e5d0f5b747c280280e9fcf69a448" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">267</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_39287cd4b49c44a4a617144fa53df1bf" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">695</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions" id="Fact_0bb19795798b4cca8d22978a26340bd0" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">24,154</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_ecf1724d9d65437ab5ccd486d8ab6ebd" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">259</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_0ad407c0955648c48850ba2d8d052462" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">263</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions" id="Fact_7d0ea3f6a325421b85ab3cbb04eb12fa" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">7,023</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 2px;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_6119186f5d854118b836ddc5c481ef2d" contextRef="c20220101to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,490</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_f3e7b13433a84e72a642c54ecc6a02b3" contextRef="c20210101to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,354</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions" id="Fact_809af95107674a60b9a6aa50165e5ba7" contextRef="c20200101to20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">1,510</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_c2747640a25a483791181f56caf8bc45" contextRef="c20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">56,567</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_58382ea6463045ef8f7cefb3fdbf3dd7" contextRef="c20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">55,085</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:UnrecognizedTaxBenefits" id="Fact_ed1574437d194d92b955e24fdec9efce" contextRef="c20201231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">54,163</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_673aed53fddd435ca232fe29a156a87633" continuedAt="Text_673aed53fddd435ca232fe29a156a87634">
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  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2022, 2021 and 2020 was $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_552285171ef248dfab36d0ee9948271e" contextRef="c20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.2</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_609bbfafde0b4ea9bce0bad6399c9eb6" contextRef="c20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.2</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate" id="Fact_49d7f6eb2570409abc1312c432abdfe0" contextRef="c20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">6.4</ix:nonFraction> million respectively, that if we recognized, could impact our
    effective tax rate, subject to our remaining valuation allowance.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We estimate that it is reasonably possible that the balance of our gross unrecognized tax benefits may decrease by approximately $<ix:nonFraction name="us-gaap:DecreaseInUnrecognizedTaxBenefitsIsReasonablyPossible" id="Fact_5c40c1715c234f5d85520d3ebbeabd1c" contextRef="c20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">15.0</ix:nonFraction> million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to tax credits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2022, 2021 and 2020, we recognized $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_5d817f0050924f7f82257fc7b70a23d7" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.8</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_2955ef1a6fab40d7ab1c8f70571532db" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.5</ix:nonFraction> million and $<ix:nonFraction name="us-gaap:UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense" id="Fact_8781f6db0d834e54aff079e85ee20d63" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">0.3</ix:nonFraction> million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to taxation in the U.S. and various state and foreign jurisdictions. The tax years 2018 through 2021 remain open to
    examination by major taxing jurisdictions, primarily federal and California, although net operating loss and credit carryforwards generated prior to 2018 may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if
    they have been used in an open period or are used in a future period.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We do not provide for a U.S. income tax liability and foreign
      withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with
      these earnings</span>.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Collaborative Arrangements and Licensing Agreements</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological
    disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with
    spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, AS, AD<sub>&#160;</sub>and
    Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 31, 2022, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_06e533557dd645a0a293de69cd61db32" contextRef="c20221231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.4</ix:nonFraction> billion from our
    Biogen collaborations.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Spinal Muscular Atrophy Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement
      with Biogen to develop and commercialize SPINRAZA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned more than $</span><ix:nonFraction name="ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_80c48219eb9e4393b8569e87d9780e38" contextRef="c20221231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.8</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including more than $</span><ix:nonFraction name="ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_6cef645a43bf4562909cf1040246fa31" contextRef="c20221231_ProductOrServiceAxis_SpinrazaRoyaltiesMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in revenue from SPINRAZA royalties and more than $</span><ix:nonFraction name="ions:CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_d44bee23603e47cfa69f81cb0d49759f" contextRef="c20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">425</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in R&amp;D revenue. We are receiving tiered royalties ranging from
    </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_61c6432e61694a50bab0c763baf066d7" contextRef="c20220101to20221231_RangeAxis_MinimumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_1823d09bb3e44264ad0c1a26037d2ae5" contextRef="c20220101to20221231_RangeAxis_MaximumMember_TypeOfArrangementAxis_BiogenCollaborationSpinrazaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">15</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from
      Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all global development,
      regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under our collaboration in 2016</span>.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_be81c80b7c244d9ab9c1fe3ba5d94592" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_b3c477905bca4fceb497de2307ce3dd8" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">45</ix:nonFraction> percent of royalty payments in 2028, on up to $<ix:nonFraction name="ions:MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" id="Fact_4e447defa6e24306b6ee0182aaf2970e" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction> billion in annual sales. Royalty
    Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_e7a75b691b8049f7929e1947376c6efa" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MinimumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">475</ix:nonFraction> million or $<ix:nonFraction name="ions:MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" id="Fact_15aab2f707114d1e916b2841ae45eb05" contextRef="c20230131_ProductOrServiceAxis_SpinrazaMember_RangeAxis_MaximumMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">550</ix:nonFraction> million, depending on the timing and occurrence of FDA approval of pelacarsen, which Novartis is developing. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New antisense medicines for the treatment of SMA</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2017, we entered into a collaboration agreement
      with Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has the option to license therapies arising out of this collaboration following the completion of
      preclinical studies. Upon licensing, Biogen </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and costs for such therapies</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the collaboration agreement, we received a </span>$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_d0f059efca0b4cb78eead790f4fa19ae" contextRef="c20171001to20171231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction>
    million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2017</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2021, we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7948382269be4b958cfc743393d71711" contextRef="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee payment when Biogen exercised its option to license ION306. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will receive development and regulatory milestone payments from Biogen if new medicines, including ION306, advance towards marketing approval.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_c2197a34ff1b4875a655950cfc588eae" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.2</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_aef687a974a64121bd0ee0bd3ff713f2" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_0c5eb25757d14bd9ad389ba766fb7464" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction> million in license fees, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_86a57530012641e6b6e3f500b7ea77c2" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million in
    development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_692c57fb61e74481aad89736cbf30dc5" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">180</ix:nonFraction> million in regulatory milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_b7d00efb08484ed684528ce5b83c3932" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">800</ix:nonFraction> million in sales milestone payments and other payments, including up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_3e6911040e1d45c0b915ba4b62552c08" contextRef="c20221231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">555</ix:nonFraction>
    million if Biogen advances ION306, which includes up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_1777f9042b9e450888607262dedee914" contextRef="c20221231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_596b7561419e42bab887182782ab4cf3" contextRef="c20221231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_693f93823cdd4834932fe11e90d4dbbc" contextRef="c20221231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">400</ix:nonFraction>
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span>mid-<ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_febbc9e4755e4074b3a325f2dacf1e28" contextRef="c20220101to20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span> From
    inception through December 31, 2022, we received $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_99913c01602a40f391a5d4b461296e90" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">85</ix:nonFraction> million in payments under this collaboration. We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7d01c2380f624d1fb49986067438d3ed" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the initiation of a Phase 3 trial under this collaboration. </span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_d072d638eb714ba6a26876ea2bbbb72a" contextRef="c20171231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_e3683f7ee88940418d4cb28dad798342" contextRef="c20171231_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6">25</ix:nonFraction> million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we
    completed our R&amp;D services performance obligation under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2021, we identified another performance obligation upon Biogen&#8217;s license of ION306 because the license we granted
    to Biogen is distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_96726e695ad843d9931f094dadfb35e4" contextRef="c20211001to20211231_ProductOrServiceAxis_Ion306Member_TypeOfArrangementAxis_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million license fee for ION306 as revenue at that time
    because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is solely responsible for the costs
    and expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2018 Strategic Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2018, we and Biogen entered into a strategic
      collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to
      develop therapies for these diseases for </span><ix:nonNumeric name="ions:TermOfCollaborationAgreement" id="Fact_3d01100b8b54487eb5650d892b0313da" contextRef="c20220101to20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" format="ixt-sec:duryear">10</ix:nonNumeric><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> years. We are
      responsible for the identification of antisense drug candidates based on selected medicines</span>. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen will have the option to license the selected medicine </span>after it completes the IND-enabling toxicology study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If Biogen exercises its
      option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the </span>second<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2018<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received </span>$<ix:nonFraction name="ions:UpfrontPaymentReceivedIncludingPurchaseOfStock" id="Fact_976237d61b074e5e9b91af22b9df351f" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-9" scale="9" format="ixt:num-dot-decimal">1</ix:nonFraction> billion from Biogen, comprised of $<ix:nonFraction name="us-gaap:ProceedsFromIssuanceOfCommonStock" id="Fact_271dd8aced544c41be19b5a818ba4058" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">625</ix:nonFraction> million
    to purchase our stock at an approximately <ix:nonFraction name="ions:PercentageCashPremiumPaidOnSharesPurchased" id="Fact_c96d0cb6c7e643c7b9c75b57384aa601" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent cash premium and $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_755b026d1fee41558d1dc2c5b62ee556" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">375</ix:nonFraction> million in an upfront payment.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of our collaboration, w<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" id="Fact_62648637171d42169a691df96b84fa12" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">270</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" id="Fact_d12a62e8d3434056a4d03512c0e598db" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_8298a32e93fb41e4b97e5b0695cdc9cb" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">105</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments and up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_0a0be2fd779c40ac96b5837d18beccfb" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments for each medicine that achieves marketing approval. </span>In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to the </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_210a08ece63647968230838a5127deb6" contextRef="c20220101to20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span>&#160;<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">W</span>e are currently advancing multiple programs under
    this collaboration and from inception through December 31, 2022, we have received nearly $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_da56d1dc03c24e66a27cff951a361cbb" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.1</ix:nonFraction> billion in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_2ccf74adb28c46398e26d42924be60cb" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.5</ix:nonFraction>
    million if Biogen designates or advances another program<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">under this collaboration. </span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we considered that
      the collaboration agreement and SPA were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. W</span>e
    identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5e47f934a68347d89f25d91842517b61" contextRef="c20180430_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Biogen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We determined our transaction price to be $</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_295623a84e6d476bb91ebff3bfed5858" contextRef="c20180430_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">552</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, comprised of $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_141e7593cbf740c7a6acd7c7ace28ee3" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">375</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from the
      upfront payment and $</span><ix:nonFraction name="ions:PremiumPaidOnSharesPurchased" id="Fact_90cf8273bd7a479187f0efa5fa9c8263" contextRef="c20180401to20180630_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">177</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the premium paid by
      Biogen for its purchase of our common stock.</span> We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our
    valuation of the premium because Biogen received restricted shares of our common stock. We allocated the transaction price to our single performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through December 31, 2022,
    we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_20ba18c7432f48b692b7d780c2e643aa" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">616</ix:nonFraction> million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in payments in the transaction price
      for our R&amp;D services performance obligation under this collaboration, including $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_3f7c210dad714493961c539d0e6cfc20" contextRef="c20210101to20211231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">23</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2021 and $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_c3f14a3ed4c14ef2b91a6574e6cdd6e4" contextRef="c20200101to20201231_TypeOfArrangementAxis_BiogenCollaboration2018StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">11</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2020. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included
      these amounts in our transaction price for our R&amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our
      effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.</span></div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2013 Strategic Neurology</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the
    treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this
    collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen has the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to
    include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing <ix:nonFraction name="ions:NumberOfMedicinesCurrentlyBeingAdvanced" id="Fact_eb09908f5c9a48cc93d43f56069f13ca" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">five</ix:nonFraction> investigational medicines in development under this collaboration, including <span style="-sec-ix-hidden:Fact_864d03b225ca4f548971b12e6b3ad3d0">a</span> medicine for Parkinson&#8217;s disease (ION859), <ix:nonFraction name="ions:NumberOfMedicinesCurrentlyBeingAdvanced" id="Fact_996f95d3d4dd49e39ee68fd344ce391e" contextRef="c20221231_ProductOrServiceAxis_MedicinesForAmyotrophicLateralSclerosisMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> medicines for ALS (tofersen and
    ION541), <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span> medicine for multiple system atrophy (ION464) and <span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29">a</span> medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in registration for SOD1 ALS.
    As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_df6e4e7a86a541f1926d3e828e7efea5" contextRef="c20130901to20130930_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">100</ix:nonFraction> million and are eligible to receive milestone payments, license fees and royalty payments for all medicines developed under this collaboration, with the specific amounts dependent upon the
    modality of the molecule advanced by Biogen. Under this collaboration, we received a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_e1fe5c7584754fa4b19bab7d646709e0" contextRef="c20180101to20181231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million license fee payment when Biogen licensed
    tofersen from us in 2018.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration for tofersen, we are eligible to receive nearly $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_eefd3cb9a90b4fa3a6dc831f3fe7cd65" contextRef="c20221231_ProductOrServiceAxis_TofersenMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">110</ix:nonFraction> million, which is comprised of the $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_fa8f6d1964ae452fb00307f7bed58d7b" contextRef="c20221231_ProductOrServiceAxis_TofersenMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million license fee received in 2018, up to
    $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_3fa5a47d30f3491ea00f26479e205e7d" contextRef="c20221231_ProductOrServiceAxis_TofersenMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">18</ix:nonFraction> million in development milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_23dea66e1d03493aa754b62abc80f638" contextRef="c20221231_ProductOrServiceAxis_TofersenMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">55</ix:nonFraction> million in regulatory milestone payments. For each of the other antisense molecules that are chosen for drug discovery and development under this collaboration, we are eligible to receive up
    to approximately $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" id="Fact_e29891c91d1a456e9cb73201cb58d5f4" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">260</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" id="Fact_f14a147cf33a4517a0dc942baa59b2db" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" id="Fact_245f4587f74e4be8b4a2a97ac77ea0f6" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">60</ix:nonFraction> million in development milestone payments, including
    amounts related to the cost of clinical trials, and up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" id="Fact_c1d1f25511534235862a7aa4449afd2d" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">130</ix:nonFraction> million in regulatory milestone payments. In addition, we are eligible to receive
    tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 31, 2022,
    we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_43252364b31243cf9fe665618b7d0d4d" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">300</ix:nonFraction> million in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_531e5e06da924c38a4eddf832276baff" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">16</ix:nonFraction> million if the FDA approves Biogen&#8217;s NDA filing of tofersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2013 strategic neurology collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_5f22f24c59d44580af822992d7804572" contextRef="c20130930_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_bcce97a700fa470ea25912768f89b9f3" contextRef="c20130930_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">100</ix:nonFraction> million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our
    transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our
    performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>During 2020, we completed our remaining<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> research and development
      services and recognized the remaining revenue related to this performance obligation. </span>From inception through the completion of our R&amp;D services performance obligation in 2020, we included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_8e6bac473c9a4873a7bb0e87fa0b76df" contextRef="c20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">145</ix:nonFraction> million in total payments in the transaction price for our R&amp;D services performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under this collaboration, we have also generated additional
      payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in the third quarter of 2022, we earned a </span>$<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ba45cef284724211a7df8091311affbd" contextRef="c20220701to20220930_TypeOfArrangementAxis_BiogenCollaboration2013StrategicNeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">9</ix:nonFraction>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million milestone payment when the FDA accepted Biogen&#8217;s NDA filing of tofersen, which we recognized in full because we did not have any performance obligations related to this milestone payment.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>
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<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat
    neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through
    the completion of the first Phase 2 study for each program. Under this collaboration, Biogen is conducting the IONIS-MAPT<sub>Rx</sub> study for AD and we are currently advancing ION582 for AS. If Biogen exercises its option to license a medicine, it
    will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, we received an upfront
      payment of $</span><ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_96e0bfc66c13486cb77a67ff0bc02893" contextRef="c20121201to20121231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. Over the term of the collaboration,
      we are eligible to receive up to $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_ccb933b83b604dc18741069989989a26" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">210</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is
      comprised of a $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_65a29b4f1fe9475eb78e5fdc8b36bd30" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_e20fa4064cdb413c915fe0a890c9479d" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments per program and up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_0925b0bf59c64d2da6aebf2c6a32d0eb" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">130</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments per program, plus a mark-up on the
      cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales of any medicines resulting from each of the </span><ix:nonFraction name="ions:NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" id="Fact_a9dc5fc90fff488ab419c13f5bd3df17" contextRef="c20121231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U020" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> programs. From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7a4c67230f974ba9bfd049a2c63e615a" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">170</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration, including nearly $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_ebfd938753694a20a31568e6f2cfa086" contextRef="c20220101to20221231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">20</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments we received from Biogen for advancing ION582 and a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_378f7d993c5644a6b5fc5620b96ebac0" contextRef="c20220101to20221231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we received from Biogen when Biogen advanced </span>IONIS-MAPT<sub>Rx</sub><sub>&#160;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during 2022. We will achieve the next payment of up to $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7bc80b0e8adf47ca8dd64914ace6d170" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>million if Biogen advances a medicine under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration, we determined we had a performance obligation to perform R&amp;D services. We allocated $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_1381ecc294394ea081d42cec69196f2b" contextRef="c20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">40</ix:nonFraction> million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our
    R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the
    total effort expected to satisfy our performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we commenced development for IONIS-MAPT<sub>Rx</sub> we identified our development work as a separate performance obligation. In the
    fourth quarter of 2022, we completed our R&amp;D services performance obligation for IONIS-MAPT<sub>Rx</sub>. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected
    to satisfy our performance obligation. From inception through December 31, 2022, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_65c25865c5cb46d88f766f99f72dcb07" contextRef="c20221231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">57</ix:nonFraction> million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation, including $<ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_df759cd0c35040108b92f1c5367ad0c1" contextRef="c20200101to20201231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">19.5</ix:nonFraction> million of milestone payments we earned from Biogen in 2020 when we advanced IONIS-MAPT<sub>Rx</sub>.</div>
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    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120</div>

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      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#8217;s license of IONIS-MAPT<sub>Rx</sub> because the
    license we granted to Biogen is distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_15e8499c99b84633ab63c1a97bb470f3" contextRef="c20191001to20191231_ProductOrServiceAxis_IonisMaptMember_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million license fee for IONIS-MAPT<sub>Rx</sub>
    as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is
    responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT<sub>Rx</sub>.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2022, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">achieved $</span><ix:nonFraction name="ions:MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" id="Fact_1f65c4ec62724cc7a189f94382c34274" contextRef="c20221001to20221231_ProductOrServiceAxis_Ion582Member_TypeOfArrangementAxis_BiogenCollaboration2012NeurologyMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">14.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments when Biogen advanced ION582. </span>We will
    recognize revenue as we perform services based on our effort to satisfy our R&amp;D services performance obligation relative to the total effort expected to satisfy our performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for ION582.</span></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6c809afdaa814005b1f6b0887bff71f2" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">56</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_f8f7b974cb2a433882a0fd53fe341a83" contextRef="c20221231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">351.2</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_35c30aecc55949b1afd1112082165450" contextRef="c20211231_TypeOfArrangementAxis_BiogenCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">407.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, related to our relationship with Biogen.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Joint Development and Commercialization Arrangement</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in
    Latin America.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_79969c9a9b914450bc63737b97f2fd7e" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">3.6</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_9dd7d53c8eee485eacad6e97dffdd4c2" contextRef="c20211201to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_7c6f989ad85b49c8b6bfede72712bef2" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">485</ix:nonFraction> million in development and approval milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_062b2352c9f546cca5d16c63150ff4fa" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.9</ix:nonFraction> billion in sales milestone payments. The agreement also includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to
    receive up to mid-<ix:nonFraction name="ions:RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" id="Fact_0b4829fbe9d847069807a9be4cf64ebe" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified <ix:nonFraction name="ions:NumberOfMaterialComponents" id="Fact_d4f80df42eb24e19af6957ccd65c9827" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U005" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization activities
    that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_4fa62bc3f1be4c069e70a0000c4e2a73" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation. For our sole performance obligation, we determined the transaction price was the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_44e63366a6fb46c893bca11b7dcc2c44" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">200</ix:nonFraction> million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_d54fda2f005e411087fa50cc25d7061d" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the <ix:nonFraction name="ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" id="Fact_cdef7d861b704faaa5f351d6c9d584db" contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">55</ix:nonFraction> percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a
    reduction of our commercial and medical affairs expenses.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of up to $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_b4e8aeaa28b84369b2caf9992e5b9833" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction>
    million upon the first regulatory approval under this collaboration. From inception through December 31, 2022, we have received nearly $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_7469eb0249ca4ffcac8492eb70284535" contextRef="c20221231_RangeAxis_MaximumMember_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">260</ix:nonFraction> million in payments under this collaboration.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research and Development Partners</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our collaboration for eplontersen, we have a collaboration with AstraZeneca focused on the treatment of cardiovascular,
    renal and metabolic diseases. In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us, including medicines in development to treat people with ATTR amyloidosis, a genetically associated form of kidney disease and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">NASH</span>. AstraZeneca is
    responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_8a9caf1ea009432aa464f4d2fbf3e279" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">5.8</ix:nonFraction> billion, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_afe0e303f52c47de8fef2665adbb52f3" contextRef="c20150701to20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million upfront payment, up to $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_7cd4f898b49c4221a2cec4bcbec84b73" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">290</ix:nonFraction> million in license fees, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_8bf17f1115c642a893b55340a0970cea" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.1</ix:nonFraction> billion
    in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_efb4704088a04a6e826d67ea5c2f326d" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">2.9</ix:nonFraction> billion in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_dec66cb0ecac4e4691af3624c8c46a68" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-8" scale="9" format="ixt:num-dot-decimal">1.5</ix:nonFraction> billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully
    commercializes under this collaboration agreement. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_2b949e7c63b941a3955f5c01227834d5" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">10</ix:nonFraction> million under this collaboration if AstraZeneca
    advances a medicine under this collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span> From inception through December 31, 2022, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_b46d3be360f94ea788b2b83ce6c73f6f" contextRef="c20221231_RangeAxis_MinimumMember_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction> million in payments under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_12852f4c3cee4a69b4f4fee5d29498e6" contextRef="c20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_321f6d91fea64a57a4103c135ba57bd1" contextRef="c20150731_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">65</ix:nonFraction> million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;D services performance obligation as we performed services
    based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation
      in</span> the fourth quarter of 2021. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our
    performance obligation, we have included $<ix:nonFraction name="ions:CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" id="Fact_ec77e25e50654249ba1ef8f5f9e4a1d1" contextRef="c20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction> million in payments in the transaction price for our R&amp;D services performance obligation.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth
    quarter of 2021, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9a05f8f53c5a4e19b3ae826d03c122b1" contextRef="c20211001to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million license fee when AstraZeneca licensed a target for a metabolic disease. We recognized the license fee as
    revenue at that time because AstraZeneca had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to AstraZeneca.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_dd338796e71247f6bc131ed50f37ef36" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">31</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_aa247af696394bd6806e0b89dffcff91" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">12</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_b22d4dca96604e1cb60121e3c991236b" contextRef="c20221231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_cfd27ca80d9f460e8f3e825d0b1607b2" contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationsMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2022 and 2021.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">GSK</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK currently includes <ix:nonFraction name="ions:NumberOfMedicinesBeingDeveloped" id="Fact_34359473758b4342a786a2bfd26d9b28" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U019" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> medicines targeting hepatitis B virus, or HBV: bepirovirsen and IONIS-HBV-L<sub>Rx</sub>. We designed these medicines to reduce the production of viral proteins associated with HBV
    infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive nearly $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_4efd385d112840afad0e4faa46214870" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">260</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_015e4506f3a84a70b7751dae7cadee18" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_229776738d884ce8aee54ac341784a2d" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">42.5</ix:nonFraction> million in development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_131e23080dcc40398152b2bd4d048056" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">120</ix:nonFraction>
    million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a5c67dd2e09b4b708ea1ffa029688a59" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million in sales milestone payments if GSK successfully develops bepirovirsen. In
    addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2022,
    we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_80b40aad4e4f428d854cce06e968dea2" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">50</ix:nonFraction> million in payments under the HBV program collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We completed our R&amp;D services performance obligations
      under our collaboration in the first quarter of 2015. </span>We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the
    license was distinct from our other performance obligations. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_eaf6203cfa224f3791cb9bffe7977090" contextRef="c20190701to20190930_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million license fee for the HBV program as revenue at that
    time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and
    royalties as GSK advances the HBV program.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In January 2023, we earned a $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_9ec3c55a66b648209abf0e9080051df5" contextRef="c20230101to20230131_SubsequentEventTypeAxis_SubsequentEventMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone when GSK initiated a Phase 3 study of bepirovirsen. We will achieve the next payment of $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_7ef9cac4d3634dc28f74729428a263ab" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">15</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing of bepirovirsen for review.</span></div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_56e66bccc3624645bcb22750e41916dd" contextRef="c20210101to20211231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ff3be5276ecf4d51a2514c2feff18233" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="0" scale="-2" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_64cbaaeaf4c249c28f7644f151cd8a75" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U003" decimals="0" scale="-2" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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</ix:continuation></ix:continuation>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_b211069271df4c4a802417ef5e7b0d32" contextRef="c20211231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_59e8ee0b0973416987e4c07862acaea5" contextRef="c20221231_TypeOfArrangementAxis_GlaxoSmithKlineCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with GSK at December 31, 2022 and 2021.</div>
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<div><br />
  </div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Novartis</div>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis
      to develop and commercialize pelacarsen and olezarsen.</span> Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in
    the fourth quarter 2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would
    negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales
    of pelacarsen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;When Novartis decided to not exercise its option for </span>olezarsen, we retained rights to develop and commercialize olezarsen.</div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc126" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc127">
<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_34bc42390fa34a3d9908bf5db5ae8531" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">900</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_5c0bfffb36654aff8e12544c8c26161d" contextRef="c20170101to20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million upfront payment, a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_57d9ab1fc2ed47699a00a295669bf20a" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction> million license fee, a $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_b0160b60708f4f9cac5ee7648f0ee321" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million
    development milestone payment, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_788a557118454c209aecf3914c029c91" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">290</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_b32f437673cc4aac8bfcce020d51b7b0" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">360</ix:nonFraction> million in sales milestone payments. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span><ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_f70b581c4c184bd7afb533f20dd7fa6d" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">275</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. </span>We are also eligible to receive tiered royalties in the
    mid-teens to low <ix:nonFraction name="ions:RoyaltyPercentageReceivedOnSalesOfMedicine" id="Fact_016f76af44eb49289c02150198f2a523" contextRef="c20220101to20221231_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent range on net sales of pelacarsen. In August 2021, we earned a $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_a546477fafc7419eb5a05bc5771e3598" contextRef="c20210801to20210831_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">25</ix:nonFraction> million milestone payment from Novartis when Novartis achieved <ix:nonFraction name="ions:PercentageEnrollmentInPhase3Study" id="Fact_5dc0a4808eb44213834bff6589f33d9b" contextRef="c20210831_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">50</ix:nonFraction> percent
    enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We recognized the milestone payment in full in the third quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment.
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of up to $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_3b19b0a102744ca58f85eea2983e6a84" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Novartis advances regulatory
      activities for pelacarsen.</span></div>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased <ix:nonFraction name="us-gaap:StockIssuedDuringPeriodSharesNewIssues" id="Fact_21e55b070897453d838adbfcb2e0f867" contextRef="c20170101to20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U002" decimals="-5" scale="6" format="ixt:num-dot-decimal">1.6</ix:nonFraction> million shares of our common stock for $<ix:nonFraction name="ions:ProceedsFromSaleOfCommonStockIncludingPremiumPaid" id="Fact_3a1b3a249b30451fa1ce1c491bcb7999" contextRef="c20170101to20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">100</ix:nonFraction>
    million in the first quarter of 2017.</div>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_45dfae68b384426d9e7f35800c5ee5da" contextRef="c20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> separate performance obligations:</div>
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<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc133" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc134">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D services for pelacarsen;</div>
        </td>

  </tr>


</table>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D services for olezarsen;</div>
        </td>

  </tr>


</table>
</ix:continuation>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">API for pelacarsen; and</div>
        </td>

  </tr>


</table>
</ix:continuation>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">API for olezarsen.</div>
        </td>

  </tr>


</table>
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<div><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that the R&amp;D services for each medicine and the API for each medicine were distinct performance obligations.</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined our transaction price to be $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_6dbe3e18253b42678289e91bfc07aa2b" contextRef="c20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">108.4</ix:nonFraction>
    million, comprised of the following:</div>
</ix:continuation>
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<div><br />
  </div>
</ix:continuation>
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<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:UpfrontPaymentReceived" id="Fact_5578c7a91e964f86994ba7891b038b6c" contextRef="c20170101to20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million from the upfront payment;</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc143" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc144">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:PremiumReceivedOnSharesIssued" id="Fact_a374896a5baf4a14a92524dbf907cb65" contextRef="c20170101to20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">28.4</ix:nonFraction> million for the premium paid by Novartis for its purchase
            of our common stock at a premium in the first quarter of 2017; and</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc144" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc145">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$<ix:nonFraction name="ions:PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" id="Fact_844ad8b58c81489eb92908f6d9b9a1e0" contextRef="c20170331_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.0</ix:nonFraction> million for the potential premium Novartis would have paid
            if they purchased our common stock in the future.</div>
        </td>

  </tr>


</table>
</ix:continuation></div>

  <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
    <div class="BRPFPageFooter">
      <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123</div>

    </div>

    <div class="BRPFPageBreak" style="page-break-after: always;">
      <hr style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;" /></div>

    <div class="BRPFPageHeader"></div>

  </div>
<div><ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc145" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc146">
<div><br />
  </div>
</ix:continuation>

  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc146" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc147">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc147" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc148">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc148" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc149">
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span><ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_40c2b997e5d94404a5664d9c274e413e" contextRef="c20170331_ProductOrServiceAxis_ResearchAndDevelopmentServicesForPelacarsenMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">64.0</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for pelacarsen;</span></div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc149" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc150">
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  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
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        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc150" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc151">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
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            million for the delivery of pelacarsen API; and</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc151" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc152">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"></td>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_060f939deb0d4433a9dd740934afd81c" contextRef="c20170331_ProductOrServiceAxis_OlezarsenActivePharmaceuticalIngredientMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">2.8</ix:nonFraction></span>
            million for the delivery of olezarsen API.</div>
        </td>

  </tr>


</table>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc152" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc153">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc153" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc154">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed our R&amp;D services performance obligations for olezarsen and pelacarsen<sub>&#160;</sub>in 2019. As such, we recognized all
    revenue we allocated to the olezarsen and pelacarsen<sub>&#160;</sub>R&amp;D services as of the end of 2019.</div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc154" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc155">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc155" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc156">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognized revenue related to the R&amp;D services for
      pelacarsen and olezarsen performance obligations as we performed services </span>based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc156" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc157">
<div><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc157" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc158"><ix:nonNumeric name="us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock" id="Text_f417927e6ea44049a9024dea0c69d56b" contextRef="c20220101to20221231_TypeOfArrangementAxis_NovartisCollaborationMember" escape="true" continuedAt="Text_b3e287a7f7e54d18bebffb386a0cf9b51">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>
</ix:nonNumeric></ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc158" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc159"><ix:continuation id="Text_b3e287a7f7e54d18bebffb386a0cf9b51" continuedAt="Text_b3e287a7f7e54d18bebffb386a0cf9b52">
<div><br />
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</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc159" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc160"><ix:continuation id="Text_b3e287a7f7e54d18bebffb386a0cf9b52">
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">

        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_130e18fe0f0c441186a0e17a58f664d9" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">3</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_3cbf0264fff04ba19d7c857cee72d9f4" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U003" decimals="0" scale="-2" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc160" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc161">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc161" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc162">
<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_202ff57e88d8402cb5c44dcb77bc2901" contextRef="c20211231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_10f623e4621745d8a337c5cf9f0bb013" contextRef="c20221231_TypeOfArrangementAxis_NovartisCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with Novartis at December 31, 2022 and 2021.</div>
</ix:continuation>
  <ix:continuation id="Text_3c1cd29c0ea248ff87b7183fbbddc2cc162" continuedAt="Text_3c1cd29c0ea248ff87b7183fbbddc2cc163">
<div><br />
  </div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As described in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Biogen SPINRAZA</span>
    section above, in January 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive <ix:nonFraction name="ions:PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" id="Fact_3449901b0f55449e94e939f4a2f1c065" contextRef="c20230131_ProductOrServiceAxis_PelacarsenActivePharmaceuticalIngredientMember_SubsequentEventTypeAxis_SubsequentEventMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">25</ix:nonFraction> percent of any future royalty payments on pelacarsen. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>
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<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2013, we formed an alliance with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people with
      early-stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for
      tominersen.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_d8d42ebb32dc46b7895c83156cf73607" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">395</ix:nonFraction> million, which is comprised of a $<ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_2675eccdc9c6499798e84c5ac5edaddf" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million upfront payment, a $<ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_28560f4cf8f840bf86e78770db9fa40e" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">45</ix:nonFraction> million license fee, up to $<ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_70a5f7bc239446719e9285ed2ff78c07" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">70</ix:nonFraction> million in
    development milestone payments, up to $<ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_884490256579410c93629768255d304a" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">170</ix:nonFraction> million in regulatory milestone payments and up to $<ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a9fce437f8684220b259d8408d43875f" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $<ix:nonFraction name="ions:MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" id="Fact_67793d8d7c8843aba2b236e8d909758e" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">136.5</ix:nonFraction> million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any product
    resulting from this alliance. From inception through December 31, 2022, we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_3aa74885781e415aa4fe5dd8e04e1eda" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">150</ix:nonFraction> million in payments under this collaboration. We will achieve the next payment of $<ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_cb403b59db80408fb4a9b96e8393b762" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">17.5</ix:nonFraction>
    million if Roche advances a medicine under this collaboration.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_efae3e04708b4937bacd7fa2bb5963f7" contextRef="c20130430_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_872b6a5c29be484ca3beb5fa683f1784" contextRef="c20130430_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">30</ix:nonFraction> million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our
    transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2019, we earned $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_7314f04e9d0e40a49fbaacf4f47109de" contextRef="c20190101to20191231_TypeOfArrangementAxis_RocheCollaborationHuntingtonsDiseaseMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction> million in milestone payments when Roche advanced tominersen under this collaboration. In March 2021, Roche decided to discontinue dosing in the Phase 3
    GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche
    is focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under
    this collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.</div>
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<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for Complement-Mediated Diseases</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2018, we entered into a collaboration agreement with Roche to<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub> for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in <ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_748d8e6ad1bb43a384bba3995dac28ea" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U021" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> disease indications for <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub>, <ix:nonFraction name="ions:NumberOfDiseaseIndications" id="Fact_33191bc87cff451284262a2fbdef6e22" contextRef="c20221231_ProductOrServiceAxis_GeographicAtrophyMember_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U021" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> for the treatment of patients with GA, the advanced stage of dry AMD, and a <span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89">second</span> for the treatment of patients with IgA nephropathy.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After positive data from a Phase 2 clinical study, </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> licensed IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">July 2022</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for $</span><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_744c3b17aa014073b17689e15adf5a2a" contextRef="c20220701to20220731_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding. In July 2022, we amended our IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that
      would require adjustments to revenue we previously recognized.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive more than $</span><ix:nonFraction name="ions:MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" id="Fact_5a1f4714bc0940e98047f54dde3feaf4" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">810</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span><ix:nonFraction name="ions:MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" id="Fact_a928686343c943b59a604f87c2139904" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment, a $</span><ix:nonFraction name="ions:MaximumAmountOfLicenseFeesOverTermOfCollaboration" id="Fact_3fe5e1d10c814bc3a6a007cda65196f9" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">35</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span><ix:nonFraction name="ions:MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" id="Fact_549abbde82e1406b93bf628bebb95927" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">145</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestones, up to $</span><ix:nonFraction name="ions:MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" id="Fact_541e131f3c6b4c92914c6be252062f60" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">279</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestones and up to $</span><ix:nonFraction name="ions:MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" id="Fact_a41faf144bd64eda8d77e690e142dd36" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">280</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high
      teens to </span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfMedicine" id="Fact_8b43151140c6441594f417ab61eb2559" contextRef="c20220101to20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales.</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>From inception through December 31, 2022,
    we have received more than $<ix:nonFraction name="ions:CumulativePaymentsReceived" id="Fact_c786e47ad0b540fbb376640b5b6b6aba" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">130</ix:nonFraction> million in payments under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will achieve the next payment of up to $</span><ix:nonFraction name="ions:NextPaymentToBeAchieved" id="Fact_5128247561064475b51c4c5bf62130be" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">90</ix:nonFraction><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> under this collaboration.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified <ix:nonFraction name="ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" id="Fact_468a8db7e8de46a69b5ee7a0575f664d" contextRef="c20181031_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U006" decimals="INF" scale="0" format="ixt-sec:numwordsen">one</ix:nonFraction> performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $<ix:nonFraction name="ions:RevenueFromContractWithCustomerTransactionPrice" id="Fact_64f9009b51e54bc8a818455d38bda2ae" contextRef="c20181031_TypeOfArrangementAxis_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">75</ix:nonFraction> million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services
    based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> currently estimate we will satisfy our performance obligation in </span>the third quarter of 2024.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>
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        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_43d5265cf6164fce9ca88f18b5897dc3" contextRef="c20210101to20211231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">17.2</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_20872827ad6c4817bcf759078e23498f" contextRef="c20200101to20201231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.9</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_50cff48cda6946bc87457fee3925e81c" contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">11</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_cf5ca05dc07c4448bdda2353f8ed8769" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">2</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_6490dfcad60e494083f50ae6646f73e4" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">1</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br />
  </div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_5ff4d7b8efd14d4a81981ea0cfa0cf58" contextRef="c20221231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">22.4</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_a38902f403274142aedd7c7ed42e8214" contextRef="c20211231_TypeOfArrangementAxis_RocheCollaborationsMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">31.6</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Roche, respectively.</span></div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercialization Partnerships</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution
    agreements with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each
    medicine.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, we entered into an exclusive license
      agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-</span><ix:nonFraction name="ions:RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" id="Fact_570d071a48d248dbb4cd460b720cd572" contextRef="c20220101to20221231_TypeOfArrangementAxis_PtcTherapeuticsCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">20</ix:nonFraction> percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on net sales for each medicine. </span>In December 2021, we started receiving
    royalties from PTC for TEGSEDI sales<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Technology Enhancement Collaborations</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle License Agreement</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a collaboration agreement with Bicycle and obtained an option to license its peptide technology to
    potentially increase the delivery capabilities of our LICA medicines. In July 2021, we paid $<ix:nonFraction name="ions:PaymentsMadeUnderCollaborationAgreement" id="Fact_5f30af4db40c410198d4adf0cf56a2ac" contextRef="c20210701to20210731_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">42</ix:nonFraction> million when we exercised our option to license
    Bicycle&#8217;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for <ix:nonNumeric name="ions:LockUpAgreementTermOfTradingRestriction" id="Fact_3b6f7ff3760d482699aca63514d611a3" contextRef="c20220101to20221231_TypeOfArrangementAxis_BicycleCollaborationMember" format="ixt-sec:durwordsen">one year</ix:nonNumeric>. In 2021, we recorded a $<ix:nonFraction name="ions:InvestmentInEquitySecuritiesFvNi" id="Fact_c4984ca504f041ad810726dda263687c" contextRef="c20210101to20211231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.2</ix:nonFraction> million equity investment for the
    shares we received in Bicycle. We recognized the remaining $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpense" id="Fact_f54d6f5ead044550b599ce90b22d6d17" contextRef="c20210101to20211231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">34.8</ix:nonFraction> million as R&amp;D expense in 2021. From inception through December 31, 2022, we have paid Bicycle $<ix:nonFraction name="ions:CumulativePaymentsMade" id="Fact_2ffb576dcfe749bd9031d801899bcdcb" contextRef="c20221231_TypeOfArrangementAxis_BicycleCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">46.6</ix:nonFraction>
    million under this collaboration agreement.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi License Agreement</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize
    investigational medicines for up to <ix:nonFraction name="ions:NumberOfTargetsToBeResearchedDevelopedAndCommercialized" id="Fact_18af6039c1e84b2ea2c0a807341f97ff" contextRef="c20221130_RangeAxis_MaximumMember_TypeOfArrangementAxis_MetagenomiCollaborationMember" unitRef="U022" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> initial genetic targets, and, upon the achievement of certain development milestones, <ix:nonFraction name="ions:NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized" id="Fact_6871a5f8bed24372ba3c40c2e27a51f5" contextRef="c20221130_RangeAxis_MaximumMember_TypeOfArrangementAxis_MetagenomiCollaborationMember" unitRef="U022" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> additional genetic targets using gene editing technologies. As a result, we paid $<ix:nonFraction name="ions:PaymentToLicenseIntellectualProperty" id="Fact_537c87b66c264e69b2abf8afc8e75f50" contextRef="c20221001to20221231_TypeOfArrangementAxis_MetagenomiCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million to license Metagenomi&#8217;s technologies. We recorded the $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost" id="Fact_e055474b91a641ecbda62b2a56a15444" contextRef="c20221001to20221231_TypeOfArrangementAxis_MetagenomiCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt:num-dot-decimal">80</ix:nonFraction> million payment as
    R&amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. We will also pay Metagenomi certain fees for the selection of genetic targets, and contingent on the
    achievement of certain development, regulatory and sales events, milestone payments and royalties. In addition, we will reimburse Metagenomi for certain of its costs in conducting its research and drug discovery activities under the collaboration.</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Other Agreements</div>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, Alnylam gave us a
      technology access fee, participation in fees from Alnylam&#8217;s partnering programs, as well as future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to <ix:nonFraction name="ions:NumberOfTherapeuticPrograms" id="Fact_b59f89497d794a21b1c2df7b377e99c3" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U020" decimals="0" scale="0" format="ixt:num-dot-decimal">4</ix:nonFraction> therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism
      and target-specific intellectual property for oligonucleotides against <ix:nonFraction name="ions:NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" id="Fact_70e205c126b840cea61764ddc5de1617" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U022" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> targets, including FXI and Apo(a) and <ix:nonFraction name="ions:NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" id="Fact_c487e303480e4ab0959ebfea8f93a143" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U022" decimals="INF" scale="0" format="ixt-sec:numwordsen">two</ix:nonFraction> other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against <ix:nonFraction name="ions:NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" id="Fact_a45941bb66ed4a98a86c4ba3cf2c4f42" contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U022" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction> other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $<ix:nonFraction name="us-gaap:LitigationSettlementAmountAwardedFromOtherParty" id="Fact_dfb16bacc6b94e7989aea7d88eebed5b" contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">41.2</ix:nonFraction> million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $<ix:nonFraction name="us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax" id="Fact_397eed8f6b004e30bfacdacc310446cf" contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">41.2</ix:nonFraction> million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Alnylam (in millions, except percentage amounts):</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_ab0a985934234f8bb07ff855cb4f906d" contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="0" scale="-2" format="ixt:fixed-zero">&#8212;</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ConcentrationRiskPercentage1" id="Fact_bd1c6a81db934c3e9265b1322ef276f8" contextRef="c20200101to20201231_ConcentrationRiskByBenchmarkAxis_RevenueFromContractWithCustomerMember_ConcentrationRiskByTypeAxis_CustomerConcentrationRiskMember_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U003" decimals="2" scale="-2" format="ixt:num-dot-decimal">7</ix:nonFraction></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did <ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_87589be5c6de472fa7c2f37215199412" contextRef="c20211231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen"><ix:nonFraction name="us-gaap:ContractWithCustomerLiability" id="Fact_12c9599416c543e7890f0ee3f45418ed" contextRef="c20221231_TypeOfArrangementAxis_AlnylamCollaborationMember" unitRef="U001" decimals="-6" scale="6" format="ixt-sec:numwordsen">no</ix:nonFraction></ix:nonFraction>t have any
    deferred revenue from our relationship with Alnylam at December 31, 2022 and 2021.</div>
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<div><ix:nonNumeric name="us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock" id="Text_44a1974bfba9485682c02d2913778f03" contextRef="c20220101to20221231" escape="true" continuedAt="Text_9295c9087d9e4122a58c2d7510da28c41">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Employment Benefits</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_06c142c7ec1040e0b05c4b2596dfe112" contextRef="c20220101to20221231_RangeAxis_MinimumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">20,500</ix:nonFraction> and $<ix:nonFraction name="us-gaap:DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount" id="Fact_2703ad6213db4e249c38d0794a2c6418" contextRef="c20220101to20221231_RangeAxis_MaximumMember" unitRef="U001" decimals="0" scale="0" format="ixt:num-dot-decimal">27,000</ix:nonFraction> in 2022 for employees under 50 years old and employees 50 years old or over,
    respectively. We made approximately $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_345fd7748408424580894d7cb0e0e108" contextRef="c20220101to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.6</ix:nonFraction> million, $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_47a2898dc66b4221ba3a2d92c2c0643a" contextRef="c20210101to20211231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.5</ix:nonFraction>
    million and $<ix:nonFraction name="us-gaap:DefinedContributionPlanCostRecognized" id="Fact_0c0b367e1550466b886c0390a13e1e0f" contextRef="c20200101to20201231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">5.7</ix:nonFraction> million in matching contributions for the years ended December 31, 2022, 2021 and 2020, respectively.</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Legal Proceedings</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
    status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
    any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
    amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On August 5, 2021, </span><ix:nonFraction name="us-gaap:LossContingencyNumberOfPlaintiffs" id="Fact_6cdf774705754659a263bf5c8a541dec" contextRef="c20210805to20210805_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U023" decimals="INF" scale="0" format="ixt-sec:numwordsen">four</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> purported former stockholders of Akcea filed an action in the Delaware
      Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#8217;s board of directors; and
      (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary
      duties in connection with the October 2020 take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any
      other lawsuit that may be filed challenging the October 2020 take-private transaction is uncertain. Accordingly, on June 3, 2022, the parties reached an agreement in principle to settle the Delaware Action for $</span><ix:nonFraction name="us-gaap:LitigationSettlementAmountAwardedToOtherParty" id="Fact_eb4ae031e3ba4e1e97657c914f4147c7" contextRef="c20220603to20220603_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">12.5</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. A Stipulation and Agreement of Compromise, Settlement and
      Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on July 5, 2022. On October 11, 2022, the Delaware Court of Chancery entered an Order and
      Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction,
      compromise and release of all claims that were asserted in the Delaware Action. The Order contains no admission of wrongdoing on the part of any of the Defendants. We recorded a net settlement expense of $</span><ix:nonFraction name="us-gaap:GainLossRelatedToLitigationSettlement" id="Fact_1cde3f8ecdf246ce9c8274576d01faf4" contextRef="c20220101to20221231_IncomeStatementLocationAxis_OtherNonoperatingIncomeExpenseMember_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">7.7</ix:nonFraction><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million within other expense in the accompanying consolidated statements of operations in 2022.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>January 19, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0059<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Shumacher Action. The complaint names Ionis&#8217; board of directors, or the
      Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also
      asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and
      proper by the court. On </span>March 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Ionis and the Board moved to dismiss the complaint. On May 24, 2022, the parties entered into a Stipulation and Agreement of
      Compromise, Settlement and Release.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>May 25, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0453<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Cohen Action. The complaint names the Board as defendants and names Ionis
      as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive
      non-executive director compensation for the years </span>2018, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>June
    2, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.</span></div>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>July 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Ionis filed a Form </span>8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of
      Action. On </span>September 21, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action
      plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. On February 7, 2023, the parties entered into
      an Amended Stipulation and Agreement of Compromise, Settlement and Release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.</span></div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Fourth Quarter Financial Data (Unaudited)</div>
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<div style="display:none;"><br /></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion
    of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2022 and 2021 are as follows (in thousands, except per share data).</div>
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          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue (1)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Revenues" id="Fact_284eab838adc45f1bab65fa3ed3e8a21" contextRef="c20221001to20221231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">151,890</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:Revenues" id="Fact_20e60632220f4799962c4c0ff5f00ab5" contextRef="c20211001to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">440,006</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses (2)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:CostsAndExpenses" id="Fact_ef4a183f40c64bdd8dd30738366a5262" contextRef="c20211001to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">219,403</ix:nonFraction></div>
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:OperatingIncomeLoss" id="Fact_e656146c3d254200b1d7c79c8135fb39" contextRef="c20211001to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">220,603</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) (3)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
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        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:ProfitLoss" id="Fact_af25cdfae24542caac610d75303df0eb" contextRef="c20211001to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,613</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

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    <td valign="bottom" style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income (loss) per share (4) (5)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_cd1a45a0547d47c59adf0ba90c1e5105" contextRef="c20221001to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.37</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_bdec6ddb89aa427eb5832c982172b15b" contextRef="c20211001to20211231" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">1.59</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: bottom; width: 76%;">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net income (loss) per share (4) (6)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(<ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_a89ed465fb1d45109c8bb5281937ec8f" contextRef="c20221001to20221231" unitRef="U004" decimals="2" sign="-" scale="0" format="ixt:num-dot-decimal">0.37</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareDiluted" id="Fact_50ffd0d9a803420490859b8fc30d4b07" contextRef="c20211001to20211231" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">1.41</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e095" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e096"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791313" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791314">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e096" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e097"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791314" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791315">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_260ceacf638c4b6691c7c678cfe81725" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $<ix:nonFraction name="us-gaap:Revenues" id="Fact_818343c16842426fb44e7d3ed2143c77" contextRef="c20211001to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember" unitRef="U001" decimals="-6" scale="6">200</ix:nonFraction> million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e097" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e098"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791315" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791316">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e098" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e099"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791316" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791317">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_94f9411e48574896ba56a419ae90ffb3" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $<ix:nonFraction name="us-gaap:ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost" id="Fact_2ed6018a59894cc5919c5df8ae3f637c" contextRef="c20221001to20221231_TypeOfArrangementAxis_MetagenomiCollaborationMember" unitRef="U001" decimals="-6" scale="6">80</ix:nonFraction> million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e099" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0910"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791317" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791318">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0910" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0911"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791318" continuedAt="Text_c7b4c274e3a7426a9369f31bea0791319">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_f63ff29e56764f3485555958bff3cab9" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">Our net loss for the three months ended
            December 31, 2022 includes the $<ix:nonFraction name="us-gaap:SaleAndLeasebackTransactionGainLossNet" id="Fact_93d3cf8aaae24601bac724efc7d56b2b" contextRef="c20221001to20221231" unitRef="U001" decimals="-5" scale="6" format="ixt:num-dot-decimal">150.1</ix:nonFraction> million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0911" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0912"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea0791319" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913110">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0912" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0913"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913110" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913111">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_bcf863dbf8484660b7f8b1e68ba84eea" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0913" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0914"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913111" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913112">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0914" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0915"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913112" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913113">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_c0533346434a4ade8e1ac885e65ef0e6" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.</ix:footnote></div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0915" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0916"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913113" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913114">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0916" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0917"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913114" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913115">
<table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:footnote id="Foot_ccc78f604f554447aaa873d5b5a1820b" footnoteRole="http://www.xbrl.org/2003/role/footnote" xml:lang="en-US">We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period</ix:footnote> as follows (in thousands except per share amounts):</div>
        </td>

  </tr>


</table>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0917" continuedAt="Text_3f95d1b66a9544fa8dc7fde445235e0918"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913115" continuedAt="Text_c7b4c274e3a7426a9369f31bea07913116">
<div><br />
  </div>
</ix:continuation></ix:continuation>
  <ix:continuation id="Text_3f95d1b66a9544fa8dc7fde445235e0918"><ix:continuation id="Text_c7b4c274e3a7426a9369f31bea07913116">
<table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;" class="cfttable">


  <tr>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 2px solid;">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31, 2021</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" colspan="2">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic" id="Fact_7d735a334951476ebc8e33e4897f0468" contextRef="c20211001to20211231" unitRef="U001" decimals="-3" scale="3" format="ixt:num-dot-decimal">224,612</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:WeightedAverageNumberOfSharesOutstandingBasic" id="Fact_7eaba9f32f18442197a37ece9b7e3320" contextRef="c20211001to20211231" unitRef="U002" decimals="-3" scale="3" format="ixt:num-dot-decimal">141,205</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><ix:nonFraction name="us-gaap:EarningsPerShareBasic" id="Fact_6de8e65be4864319852a79f01f6292c1" contextRef="c20211001to20211231" unitRef="U004" decimals="2" scale="0" format="ixt:num-dot-decimal">1.59</ix:nonFraction></div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

  </tr>

  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; background-color: #CCEEFF;">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div>
        </td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

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    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 2px;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" colspan="1">&#160;</td>

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  <tr>

    <td valign="bottom" style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;">
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    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" colspan="1">&#160;</td>

    <td valign="bottom" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" colspan="1">&#160;</td>

    <td valign="bottom" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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    <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" colspan="1">
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<DOCUMENT>
<TYPE>EX-10.10
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<FILENAME>exhibit10-10.htm
<DESCRIPTION>EXHIBIT 10.1
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  <p style="margin: 0; font: 10pt Times New Roman, Times, Serif; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit 10.10</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps"><b>Amended and Restated </b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Ionis Pharmaceuticals, Inc.</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Non-Statutory</u>&#160;Stock Option Agreement</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps">Ionis Pharmaceuticals, Inc.</font> <font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(the &#8220;Company&#8221;), pursuant to its Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan (the &#8220;Plan&#8221;), hereby grants to Optionholder an option to purchase the number of shares of the
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  </table>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><i>Page 1 of 2002 NED Plan Option Agreement</i></font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        Amended and Restated 2002 Non-Employee Directors&#8217; Stock Option Plan<br>
        Stock Option Agreement <br>
        (Nonstatutory Stock Option)</b></font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pursuant to your Stock Option Grant Notice (&#8220;Grant Notice&#8221;) and this
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      Plan.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Method of
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Whole Shares.</font></b>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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          Compliance.</font></b> Notwithstanding anything to the contrary contained herein, you may not exercise your option unless the shares of Common Stock issuable upon such exercise are then registered under the Securities Act or, if such shares of
      Common Stock are not then so registered, the Company has determined that such exercise and issuance would be exempt from the registration requirements of the Securities Act. The exercise of your option must also comply with other applicable laws and
      regulations governing your option, and you may not exercise your option if the Company determines that such exercise would not be in material compliance with such laws and regulations.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Term.</font></b>
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      of the following:</font></p>
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      the preceding paragraph relating to &#8220;Securities Law Compliance,&#8221; your option shall not expire until the earlier of the Expiration Date or until it shall have been exercisable for an aggregate period of 3 months after the termination of your
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><i>Page 2 of 2002 NED Plan Option Agreement</i></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b>By exercising your option you agree that, as a
      condition to any exercise of your option, the Company may require you to enter into an arrangement providing for the payment by you to the Company of any tax withholding obligation of the Company arising by reason of (1) the exercise of your option,
      (2) the lapse of any substantial risk of forfeiture to which the shares of Common Stock are subject at the time of exercise, or (3) the disposition of shares of Common Stock acquired upon such exercise.</font></p>
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      This option is not transferable except by will or by the laws of descent and distribution, and is exercisable during your lifetime only by you; notwithstanding the foregoing, you may transfer part or all of this option to any of the following:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;your spouse, children (by birth or adoption), stepchildren,
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      or the benefit of your spouse, children (by birth or adoption), stepchildren, grandchildren, or parents for estate planning purposes; or,</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;an organization which is exempt from taxation under Section
      501(c)(3) of the Code or to which tax-deductible charitable contributions may be made under Section 170 of the Code.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      form satisfactory to the Company, designate a third party who, in the event of your death, will thereafter be entitled to exercise the option.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>9.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Right of
          Repurchase.</font></b> To the extent provided in the Company&#8217;s bylaws as amended from time to time, the Company shall have the right to repurchase all or any part of the shares of Common Stock you acquire pursuant to the exercise of your option.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Option not a
          Service Contract.</font></b> Your option is not an employment or service contract, and nothing in your option shall be deemed to create in any way whatsoever any obligation on your part to continue in the employ of the Company or an Affiliate, or
      of the Company or an Affiliate to continue your employment. In addition, nothing in your option shall obligate the Company or an Affiliate, their respective stockholders, Boards of Directors, Officers or Employees to continue any relationship that
      you might have as a Director or Consultant for the Company or an Affiliate.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>11.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Withholding
          Obligations. </font></b>You may not exercise your option unless the tax withholding obligations of the Company and/or any Affiliate are satisfied. Accordingly, you may not be able to exercise your option when desired even though your option is
      vested, and the Company shall have no obligation to issue a certificate for such shares of Common Stock or release such shares of Common Stock from any escrow provided for herein.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>12.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Notices.</font></b>
      Any notices provided for in your option or the Plan shall be given in writing and shall be deemed effectively given upon receipt or, in the case of notices delivered by mail by the Company to you, 5 days after deposit in the United States mail,
      postage prepaid, addressed to you at the last address you provided to the Company.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>13.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Governing Plan
          Document.</font></b> Your option is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your option, and is further subject to all interpretations, amendments, rules and regulations which may from time to
      time be promulgated and adopted pursuant to the Plan. In the event of any conflict between the provisions of your option and those of the Plan, the provisions of the Plan shall control.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><i>Page 3 of 2002 NED Plan Option Agreement&#160;</i></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: right; text-indent: 0"><b>Exhibit 10.13</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0">&#160;</p>
  <p style="font: small-caps bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps">Ionis Pharmaceuticals, Inc.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps;">2011 Equity Incentive Plan</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-size: 12pt; font-variant: small-caps; text-transform: none">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps">Option Agreement</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><font style="font-size: 10pt">(Nonstatutory Stock Option)</font></font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center">F<font style="font-size: 8pt">or </font>O<font style="font-size: 8pt">ptions</font> G<font style="font-size: 8pt">ranted</font> A<font style="font-size: 8pt">fter </font>J<font style="font-size: 8pt">anuary</font> 1, 2022</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Pursuant to your Stock Option Grant Notice (&#8220;<b><i>Grant Notice</i></b>&#8221;) and this Option Agreement, Ionis Pharmaceuticals, Inc. (the &#8220;<b><i>Company</i></b>&#8221;)





    has granted you an option under its 2011 Equity Incentive Plan (the &#8220;<b><i>Plan</i></b>&#8221;) to purchase the number of shares of the Company&#8217;s Common Stock indicated in your Grant Notice at the exercise price indicated in your Grant Notice. Capitalized
    terms not explicitly defined in this Option Agreement but defined in the Plan shall have the same definitions as in the Plan.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The details of your option are as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Vesting.</font></b> Subject to the limitations
    contained herein, your option will vest as provided in your Grant Notice, provided that vesting will cease upon the termination of your Continuous Service.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Number of Shares and Exercise Price.</font></b>
    The number of shares of Common Stock subject to your option and your exercise price per share referenced in your Grant Notice may be adjusted from time to time for Capitalization Adjustments.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Exercise Restriction for Non-Exempt Employees.</font></b>
    In the event that you are an Employee eligible for overtime compensation under the Fair Labor Standards Act of 1938, as amended (<i>i.e.</i>, a &#8220;<b><i>Non-Exempt Employee</i></b>&#8221;), you may not exercise your option until you have completed at least six
    months of Continuous Service measured from the Date of Grant specified in your Grant Notice, notwithstanding any other provision of your option.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Method of Payment.</font></b> Payment of the
    exercise price is due in full upon exercise of all or any part of your option. You may elect to make payment of the exercise price in cash or by check or in any other manner <b><i>permitted by your Grant Notice,</i></b> which may include one or more
    of the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>Provided that at the time of exercise the Common Stock is publicly traded, pursuant to a
    program developed under Regulation T as promulgated by the Federal Reserve Board that, prior to the issuance of Common Stock, results in either the receipt of cash (or check) by the Company or the receipt of irrevocable instructions to pay the
    aggregate exercise price to the Company from the sales proceeds.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>Subject to the consent of the Company at the time of exercise, by a &#8220;net exercise&#8221; arrangement
    pursuant to which the Company will reduce the number of shares of Common Stock issued upon exercise of your option by the largest whole number of shares with a Fair Market Value that does not exceed the aggregate exercise price; provided, however, that
    the Company shall accept a cash or other payment from you to the extent of any remaining balance of the aggregate exercise price not satisfied by such reduction in the number of whole shares to be issued; provided further, however, that shares of
    Common Stock will no longer be outstanding under your option and will not be exercisable thereafter to the extent that (1) shares are used to pay the exercise price pursuant to the &#8220;net exercise,&#8221; (2) shares are delivered to you as a result of such
    exercise, and (3) shares are withheld to satisfy tax withholding obligations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Whole Shares.</font></b> You may exercise your
    option only for whole shares of Common Stock.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Securities Law Compliance.</font></b>
    Notwithstanding anything to the contrary contained herein, you may not exercise your option unless the shares of Common Stock issuable upon such exercise are then registered under the Securities Act or, if such shares of Common Stock are not then so
    registered, the Company has determined that such exercise and issuance would be exempt from the registration requirements of the Securities Act. The exercise of your option also must comply with other applicable laws and regulations governing your
    option, and you may not exercise your option if the Company determines that such exercise would not be in material compliance with such laws and regulations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Term.</font></b> You may not exercise your
    option before the commencement or after the expiration of its term. The term of your option commences on the Date of Grant and expires upon the earliest of the following:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>three months after the termination of your Continuous Service for any reason other than upon
    your Disability, retirement or death; provided, however, that if during any part of such three month period your option is not exercisable solely because of the condition set forth in the section above relating to &#8220;Securities Law Compliance,&#8221; your
    option shall not expire until the earlier of the Expiration Date or until it shall have been exercisable for an aggregate period of three months after the termination of your Continuous Service; and if (i) you are a Non-Exempt Employee, (ii) your
    Continuous Service terminates within six months after the Date of Grant specified in your Grant Notice, and (iii) you have vested in a portion of your option at the time of your termination of Continuous Service, your option shall not expire until the
    earlier of (x) the later of (A) the date that is seven months after the Date of Grant specified in your Grant Notice or (B) the date that is three months after the termination of your Continuous Service, or (y) the Expiration Date;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>12 months after the termination of your Continuous Service due to your Disability;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>18 months after the termination of your Continuous Service due to your retirement; provided
    that (i) you were over the age of 55 at the time of such retirement and (ii) you had been providing Continuous Service to the Company as an Employee, Director or Consultant (or any combination thereof) for a continuous and uninterrupted period of at
    least five years prior to such retirement;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>the Expiration Date indicated in your Grant Notice; or</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>the day before the tenth (10<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>) anniversary of the Date of Grant.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Notwithstanding the foregoing, if you die during the period provided in Section 7(a), 7(b) or 7(c) above, the term of your option shall not expire
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>You may exercise the vested portion of your option (and the unvested portion of your option if
    your Grant Notice so permits) during its term by delivering a Notice of Exercise (in a form designated by the Company) together with the exercise price to the Secretary of the Company, or to such other person as the Company may designate, during
    regular business hours, together with such additional documents as the Company may then require.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>By exercising your option you agree that, as a condition to any exercise of your option, the
    Company may require you to enter into an arrangement providing for the payment by you to the Company of any tax withholding obligation of the Company arising by reason of (1) the exercise of your option, (2) the lapse of any substantial risk of
    forfeiture to which the shares of Common Stock are subject at the time of exercise, or (3) the disposition of shares of Common Stock acquired upon such exercise.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>If (i) you have not exercised your option in full by the 10th business day prior to the
    expiration of this option, <u>(ii) at such time you are a current employee of the Company or were an employee of the Company within the previous 90 days</u>, (iii) you have not otherwise instructed the broker to exercise this option prior to expiry
    under a separate Company-approved Rule 10b5-1 Plan, and (iv) the prevailing market price of the Common Stock exceeds the Exercise Price per share of this option, then you authorize the Company&#8217;s external stock plan administrator (&#8220;Administrator&#8221;) to,
    in its sole discretion, without obligation, and in compliance with all applicable legal conditions and restrictions, exercise this option on your behalf and sell the number of whole shares of Common Stock having a Fair Market Value sufficient to cover
    the aggregate exercise price plus the minimum amount of tax required to be withheld by law (such number of shares to be determined by the Company as of the date of exercise), and to remit payment of such exercise price and withholding amounts to the
    Company. In addition, you authorize the Company to, in its sole discretion and in compliance with all applicable legal conditions and restrictions, take any action it deems necessary or appropriate to effect such an exercise and sale.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">Notwithstanding the foregoing, the Company may, in its sole discretion, without obligation, and in lieu of the automatic exercise and sale set forth
    above, effect a &#8220;net exercise&#8221; arrangement to cover the aggregate exercise price and minimum amount of the tax to be withheld by the Company by law, each as further described in Section 5(c)(iv) and Section 8(f) of the Plan.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">You will take all necessary and appropriate actions to effect the exercise and sale under this section, including but not limited to completing
    any exercise forms or authorizations. You hereby authorize and appoint each of Administrator and the Company&#8217;s Corporate Secretary to serve, individually or collectively, as your agent and attorney-in-fact and, in accordance with the terms of this
    section, to effect the exercise and sale of your option. <font style="font-size: 10pt">You will pay the Company an administrative fee of $100 in connection with any exercise or sale under this section.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">This Section 8(c) is intended to meet the requirements of, and comply with, Rule 10b5-1 (c) under the Exchange Act.</p>
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    transferable, except (1) by will or by the laws of descent and distribution, (2) pursuant to a domestic relations order, (3) with the prior written approval of the Company, by instrument to an <i>inter vivos</i> or testamentary trust, in a form
    accepted by the Company, in which the option is to be passed to beneficiaries upon the death of the trustor (settlor) and (4) with the prior written approval of the Company, by gift, in a form accepted by the Company, to a permitted transferee under
    Rule 701 of the Securities Act.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Option not a Service Contract.</font></b> Your
    option is not an employment or service contract, and nothing in your option shall be deemed to create in any way whatsoever any obligation on your part to continue in the employ of the Company or an Affiliate, or of the Company or an Affiliate to
    continue your employment. In addition, nothing in your option shall obligate the Company or an Affiliate, their respective stockholders, Boards of Directors, Officers or Employees to continue any relationship that you might have as a Director or
    Consultant for the Company or an Affiliate.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>At the time you exercise your option, in whole or in part, or at any time thereafter as
    requested by the Company, you hereby authorize withholding from payroll and any other amounts payable to you, and otherwise agree to make adequate provision for (including by means of a &#8220;cashless exercise&#8221; pursuant to a program developed under
    Regulation T as promulgated by the Federal Reserve Board to the extent permitted by the Company), any sums required to satisfy the federal, state, local and foreign tax withholding obligations of the Company or an Affiliate, if any, which arise in
    connection with your option.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font>Upon your request and subject to approval by the Company, in its sole discretion, and
    compliance with any applicable legal conditions or restrictions, the Company may withhold from fully vested shares of Common Stock otherwise issuable to you upon the exercise of your option a number of whole shares of Common Stock having a Fair Market
    Value, determined by the Company as of the date of exercise, not in excess of the minimum amount of tax required to be withheld by law (or such lower amount as may be necessary to avoid classification of your option as a liability for financial
    accounting purposes). If the date of determination of any tax withholding obligation is deferred to a date later than the date of exercise of your option, share withholding pursuant to the preceding sentence shall not be permitted unless you make a
    proper and timely election under Section 83(b) of the Code, covering the aggregate number of shares of Common Stock acquired upon such exercise with respect to which such determination is otherwise deferred, to accelerate the determination of such tax
    withholding obligation to the date of exercise of your option. Notwithstanding the filing of such election, shares of Common Stock shall be withheld solely from fully vested shares of Common Stock determined as of the date of exercise of your option
    that are otherwise issuable to you upon such exercise. Any adverse consequences to you arising in connection with such share withholding procedure shall be your sole responsibility.</p>
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    any Affiliate are satisfied. Accordingly, you may not be able to exercise your option when desired even though your option is vested, and the Company shall have no obligation to issue a certificate for such shares of Common Stock unless such
    obligations are satisfied.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt"><b>12.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b></font><b><font style="font-variant: small-caps">Tax Consequences</font></b>. You hereby agree
    that the Company does not have a duty to design or administer the Plan or its other compensation programs in a manner that minimizes your tax liabilities. You shall not make any claim against the Company, or any of its Officers, Directors, Employees or
    Affiliates related to tax liabilities arising from your option or your other compensation. In particular, you acknowledge that this option is exempt from Section 409A of the Code only if the exercise price per share specified in the Grant Notice is at
    least equal to the &#8220;fair market value&#8221; per share of the Common Stock on the Date of Grant and there is no other impermissible deferral of compensation associated with the option.</p>
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    your option or the Plan shall be given in writing and shall be deemed effectively given upon receipt or, in the case of notices delivered by mail by the Company to you, five days after deposit in the United States mail, postage prepaid, addressed to
    you at the last address you provided to the Company.</p>
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    is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your option, and is further subject to all interpretations, amendments, rules and regulations, which may from time to time be promulgated and adopted
    pursuant to the Plan. In the event of any conflict between the provisions of your option and those of the Plan, the provisions of the Plan shall control.</p>
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<DESCRIPTION>EXHIBIT 10.14
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  <p style="margin-top: 0; text-align: center; margin-bottom: 0"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps"><b>Ionis Pharmaceuticals, Inc.</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps"><b>2011 Equity Incentive Plan</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps"><b>Restricted Stock Unit Agreement</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pursuant to the Restricted Stock Unit Grant Notice (&#8220;<b><i>Grant Notice</i></b>&#8221;)



      and this Restricted Stock Unit Agreement and in consideration of your services, Ionis Pharmaceuticals, Inc. (the&#160;&#8220;<b><i>Company</i></b>&#8221;) has awarded you a Restricted Stock Unit Award (the &#8220;<b><i>Award</i></b>&#8221;) under its 2011 Equity Incentive Plan
      (the &#8220;<b><i>Plan</i></b>&#8221;). Your Award is granted to you effective as of the Date of Grant set forth in the Grant Notice for this Award. This Restricted Stock Unit Award Agreement shall be deemed to be agreed to by the Company and you upon the
      earlier of (i) signing (or electronic acceptance) by you of the Restricted Stock Unit Grant Notice to which it is attached, and (ii) your receipt of shares of Common Stock under this Restricted Stock Unit Agreement. Capitalized terms not explicitly
      defined in this Restricted Stock Unit Agreement shall have the same meanings given to them in the Plan or the Grant Notice, as applicable. In the event of any conflict between the terms in this Restricted Stock Unit Agreement and the Plan, the terms
      of the Plan shall control. The details of your Award, in addition to those set forth in the Grant Notice and the Plan, are as follows.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Grant of the
          Award.</font></b> This Award represents the right to be issued on a future date the number of shares of the Company&#8217;s Common Stock that is equal to the number of stock units indicated in the Grant Notice (the &#8220;<b><i>Stock Units</i></b>&#8221;). As of
      the Date of Grant, the Company will credit to a bookkeeping account maintained by the Company for your benefit (the &#8220;<b><i>Account</i></b>&#8221;) the number of Stock Units subject to the Award. This Award was granted in consideration of your services to
      the Company. Except as otherwise provided herein, you will not be required to make any payment to the Company (other than past and future services to the Company) with respect to your receipt of the Award, the vesting of the Stock Units or the
      delivery of the Common Stock to be issued in respect of the Award.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; In General.</b> Subject to the limitations contained
      herein, your Award will vest, if at all, in accordance with the vesting schedule provided in the Grant Notice, provided that vesting will cease upon the termination of your Continuous Service. Upon such termination of your Continuous Service, the
      Stock Units credited to the Account that were not vested on the date of such termination will be forfeited at no cost to the Company and you will have no further right, title or interest in the Stock Units or the shares of Common Stock to be issued
      in respect of the Award.</font></p>
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      be adjusted from time to time for Capitalization Adjustments, as provided in the Plan.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>Any additional Stock Units that become subject to the
      Award pursuant to this Section 3 and Section 7, if any, shall be subject, in a manner determined by the Board, to the same forfeiture restrictions, restrictions on transferability, and time and manner of delivery as applicable to the other Stock
      Units covered by your Award.</font></p>
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      in this Section 5. For example, you may not use shares that may be issued in respect of your Award as security for a loan. The restrictions on transfer set forth herein will lapse upon delivery to you of shares in respect of your vested Award.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Death</b>. Your Award is transferable by will and by the
      laws of descent and distribution. In addition, upon receiving written permission from the Board or its duly authorized designee, you may, by delivering written notice to the Company, in a form provided by or otherwise satisfactory to the Company and
      any broker designated by the Company to effect transactions under the Plan, designate a third party who, in the event of your death, shall thereafter be entitled to receive any distribution of Common Stock or other consideration to which you were
      entitled at the time of your death pursuant to this Agreement. In the absence of such a designation, your executor or administrator of your estate shall be entitled to receive, on behalf of your estate, such Common Stock or other consideration.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Certain Trusts.</b> Upon receiving written permission from
      the Board or its duly authorized designee, you may transfer your Award to a trust if you are considered to be the sole beneficial owner (determined under Section 671 of the Code and applicable state law) while the Award is held in the trust, provided
      that you and the trustee enter into transfer and other agreements required by the Company.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Domestic Relations Orders.</b> Upon receiving written
      permission from the Board or its duly authorized designee, and provided that you and the designated transferee enter into transfer and other agreements required by the Company, you may transfer your Award or your right to receive the distribution of
      Common Stock or other consideration thereunder, pursuant to a domestic relations order that contains the information required by the Company to effectuate the transfer. You are encouraged to discuss the proposed terms of any division of this Award
      with the Company prior to finalizing the domestic relations order to help ensure the required information is contained within the domestic relations order.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2.</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Date of
          Issuance. </font></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>If the Award is exempt from application of Section
      409A of the Code and the regulations and other guidance thereunder and any state law of similar effect (collectively <b>&#8220;<i>Section 409A</i>&#8221;</b>), the Company will deliver to you a number of shares of the Company&#8217;s Common Stock equal to the number
      of vested Stock Units subject to your Award, including any additional Stock Units received pursuant to Section 3 above that relate to those vested Stock Units on the applicable vesting date(s). However, if a scheduled delivery date falls on a date
      that is not a business day, such delivery date shall instead fall on the next following business day. Notwithstanding the foregoing, in the event that (i) you are subject to the Company&#8217;s policy permitting officers and directors to sell shares only
      during certain &#8220;window&#8221; periods, in effect from time to time (the &#8220;<b><i>Policy</i></b>&#8221;) or you are otherwise prohibited from selling shares of the Company&#8217;s Common Stock in the public market and any shares covered by your Award are scheduled to be
      delivered on a day (the &#8220;<b><i>Original Distribution Date</i></b>&#8221;) that does not occur during an open &#8220;window period&#8221; applicable to you or a day on which you are permitted to sell shares of the Company&#8217;s common stock pursuant to a written plan that
      meets the requirements of Rule 10b5-1 under the Exchange Act, in each case as determined by the Company in accordance with the Policy, or does not occur on a date when you are otherwise permitted to sell shares of the Company&#8217;s common stock on the
      open market, and (ii) the Company elects not to satisfy its tax withholding obligations by withholding shares from your distribution, then such shares shall not be delivered on such Original Distribution Date and shall instead be delivered on the
      first business day of the next occurring open &#8220;window period&#8221; applicable to you pursuant to such policy (regardless of whether you are still providing continuous services at such time) or the next business day when you are not prohibited from selling
      shares of the Company&#8217;s Common Stock in the open market, but in no event later than the fifteenth day of the third calendar month of the calendar year following the calendar year in which the shares covered by the Award vest. Delivery of the shares
      pursuant to the provisions of this Section 6(a) is intended to comply with the requirements for the short-term deferral exemption available under Treasury Regulation 1.409A-1(b)(4) and shall be construed and administered in such manner. The form of
      such delivery of the shares (<i>e.g.</i>, a stock certificate or electronic entry evidencing such shares) shall be determined by the Company.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>The provisions of this Section 6(b) are intended to
      apply if the Award is subject to Section 409A because of the terms of a severance arrangement or other agreement between you and the Company, if any, that provides for acceleration of vesting of the Award upon your separation from service (as such
      term is defined in section 409A(a)(2)(A)(i) of the Code and applicable guidance thereunder (&#8220;<b><i>Separation From Service</i></b>&#8221;) and such severance benefit does not satisfy the requirements for an exemption from application of Section 409A
      provided under Treasury Regulations Sections 1.409A-1(b)(4) or 1.409A-1(b)(9) (&#8220;<b><i>Non-Exempt Severance Arrangement</i></b>&#8221;). If the Award is subject to and not exempt from application of Section 409A due to application of a Non-Exempt Severance
      Arrangement, the following provisions in this Section 6(b) shall supersede anything to the contrary in Section 6(a).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b>If the Award vests in ordinary course during your
      Continuous Service in accordance with the vesting schedule set forth in the Grant Notice, in no event will the shares to be issued in respect of your Award be issued any later than the later of: (i) December 31<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">st</sup> of the calendar year that includes the applicable vesting date, or (ii) the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the applicable vesting
      date.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3.</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b>If the Award accelerates vesting under the terms of
      your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were in effect as of the date of grant of the Award and therefore part of the
      terms of the Award as of the date of grant, then the shares will be earlier issued in respect of your Award upon your Separation From Service in accordance with the terms of the Non-Exempt Severance Arrangement, but in no event later than the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the date of your Separation From Service. However, if at the time the shares would otherwise be issued you are subject to the distribution limitations
      contained in section 409A of the Code applicable to &#8220;specified employees&#8221; as defined in section 409A(a)(2)(B)(i) of the Code and applicable guidance thereunder, such share issuances shall not be made before the date which is six months following the
      date of your Separation From Service, or, if earlier, the date of your death that occurs within such six month period.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;</b>If the Award accelerates vesting under the terms of
      your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were not in effect as of the date of grant of the Award and therefore not a part
      of the terms of the Award on the date of grant, then such acceleration of vesting of the Award shall not accelerate the issuance date of the shares, but the shares shall instead be issued on the same schedule as set forth on the Grant Notice as if
      they had vested in ordinary course during your Continuous Service, notwithstanding the vesting acceleration of the Award. Such issuance schedule is intended to satisfy the requirements of payment on a specified date or pursuant to a fixed schedule,
      as provided under Treas. Reg. 1.409A-3(a)(4).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>The provisions in this Agreement for delivery of the
      shares in respect of the Award are intended either to comply with the requirements of Section 409A or to provide a basis for exemption from such requirements so that the delivery of the shares will not trigger the additional tax imposed under Section
      409A, and any ambiguities herein will be so interpreted.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Dividends.</font></b>
      You shall be entitled to receive payments equal to any cash dividends and other distributions paid with respect to a corresponding number of shares to be issued in respect of the Stock Units covered by your Award, provided that if any such dividends
      or distributions are paid in shares, the Fair Market Value of such shares shall be converted into additional Stock Units covered by the Award, and further provided that such additional Stock Units shall be subject to the same forfeiture restrictions
      and restrictions on transferability as apply to the Stock Units subject to the Award with respect to which they relate.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Restrictive
          Legends.</font></b> The shares issued in respect of your Award shall be endorsed with appropriate legends determined by the Company.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>9.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Award not a
          Service Contract</font>.</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>Your Continuous Service with the Company or an
      Affiliate is not for any specified term and may be terminated by you or by the Company or an Affiliate at any time, for any reason, with or without cause and with or without notice.&#160; Nothing in this Restricted Stock Unit Agreement (including, but not
      limited to, the vesting of your Award pursuant to the schedule set forth in Section 2 herein or the issuance of the shares in respect of your Award), the Plan or any covenant of good faith and fair dealing that may be found implicit in this
      Restricted Stock Unit Agreement or the Plan shall:&#160; (i) confer upon you any right to continue in the employ of, or affiliation with, the Company or an Affiliate; (ii) constitute any promise or commitment by the Company or an Affiliate regarding the
      fact or nature of future positions, future work assignments, future compensation or any other term or condition of employment or affiliation; (iii) confer any right or benefit under this Restricted Stock Unit Agreement or the Plan unless such right
      or benefit has specifically accrued under the terms of this Agreement or Plan; or (iv) deprive the Company of the right to terminate you at will and without regard to any future vesting opportunity that you may have.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4.</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>By accepting this Award, you acknowledge and agree
      that the right to continue vesting in the Award pursuant to the schedule set forth in Section 2 is earned only by continuing as an employee, director or consultant at the will of the Company (not through the act of being hired, being granted this
      Award or any other award or benefit) and that the Company has the right to reorganize, sell, spin-out or otherwise restructure one or more of its businesses or Affiliates at any time or from time to time, as it deems appropriate (a
      &#8220;reorganization&#8221;).&#160; You further acknowledge and agree that such a reorganization could result in the termination of your Continuous Service, or the termination of Affiliate status of your employer and the loss of benefits available to you under this
      Restricted Stock Unit Agreement, including but not limited to, the termination of the right to continue vesting in the Award. You further acknowledge and agree that this Restricted Stock Unit Agreement, the Plan, the transactions contemplated
      hereunder and the vesting schedule set forth herein or any covenant of good faith and fair dealing that may be found implicit in any of them do not constitute an express or implied promise of continued engagement as an employee or consultant for the
      term of this Agreement, for any period, or at all, and shall not interfere in any way with your right or the Company&#8217;s right to terminate your Continuous Service at any time, with or without cause and with or without notice.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <font style="font-variant: small-caps">Withholding
          Obligations.</font></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>On or before the time you receive a distribution of
      the shares subject to your Award, or at any time thereafter as requested by the Company, you hereby authorize any required withholding from the Common Stock issuable to you and/or otherwise agree to make adequate provision in cash for any sums
      required to satisfy the federal, state, local and foreign tax withholding obligations of the Company or any Affiliate which arise in connection with your Award (the &#8220;<b><i>Withholding Taxes</i></b>&#8221;). Additionally, the Company may, in its sole
      discretion, satisfy all or any portion of the Withholding Taxes obligation relating to your Award by any of the following means or by a combination of such means: (i) withholding from any compensation otherwise payable to you by the Company; (ii)
      causing you to tender a cash payment; or (iii) withholding shares of Common Stock from the shares of Common Stock issued or otherwise issuable to you in connection with the Award with a Fair Market Value (measured as of the date shares of Common
      Stock are issued to pursuant to Section 6) equal to the amount of such Withholding Taxes; provided, however, that the number of such shares of Common Stock so withheld shall not exceed the amount necessary to satisfy the Company&#8217;s required tax
      withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll taxes, that are applicable to supplemental taxable income.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5.</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>Unless the tax withholding obligations of the Company
      and/or any Affiliate are satisfied, the Company shall have no obligation to deliver to you any Common Stock.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>In the event the Company&#8217;s obligation to withhold
      arises prior to the delivery to you of Common Stock or it is determined after the delivery of Common Stock to you that the amount of the Company&#8217;s withholding obligation was greater than the amount withheld by the Company, you agree to indemnify and
      hold the Company harmless from any failure by the Company to withhold the proper amount.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>If specified in your Grant Notice and permitted by the
      Company, you may direct the Company to withhold shares of Common Stock with a Fair Market Value (measured as of the date shares of Common Stock are issued pursuant to Section 6) equal to the amount of such Withholding Taxes; provided, however, that
      the number of such shares of Common Stock so withheld shall not exceed the amount necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax
      purposes, including payroll taxes, that are applicable to supplemental taxable income.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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          Obligation.</font></b> Your Award is unfunded, and as a holder of a vested Award, you shall be considered an unsecured creditor of the Company with respect to the Company&#8217;s obligation, if any, to issue shares pursuant to this Agreement. You shall
      not have voting or any other rights as a stockholder of the Company with respect to the shares to be issued pursuant to this Agreement until such shares are issued to you pursuant to Section 6 of this Agreement. Upon such issuance, you will obtain
      full voting and other rights as a stockholder of the Company. Nothing contained in this Agreement, and no action taken pursuant to its provisions, shall create or be construed to create a trust of any kind or a fiduciary relationship between you and
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      Any notices provided for in your Award or the Plan shall be given in writing and shall be deemed effectively given upon receipt or, in the case of notices delivered by the Company to you, five days after deposit in the United States mail, postage
      prepaid, addressed to you at the last address you provided to the Company. Notwithstanding the foregoing, the Company may, in its sole discretion, decide to deliver any documents related to participation in the Plan and this Award by electronic means
      or to request your consent to participate in the Plan by electronic means. You hereby consent to receive such documents by electronic delivery and, if requested, to agree to participate in the Plan through an on-line or electronic system established
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      Award shall be transferable to any one or more persons or entities, and all covenants and agreements hereunder shall inure to the benefit of, and be enforceable by the Company&#8217;s successors and assigns. Your rights and obligations under your Award may
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          Document</font>.</b> Your Award is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your Award, and is further subject to all interpretations, amendments, rules and regulations which may from time to
      time be promulgated and adopted pursuant to the Plan. Except as expressly provided herein, in the event of any conflict between the provisions of your Award and those of the Plan, the provisions of the Plan shall control.</font></p>
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      If all or any part of this Agreement or the Plan is declared by any court or governmental authority to be unlawful or invalid, such unlawfulness or invalidity shall not invalidate any portion of this Agreement or the Plan not declared to be unlawful
      or invalid. Any Section of this Agreement (or part of such a Section) so declared to be unlawful or invalid shall, if possible, be construed in a manner which will give effect to the terms of such Section or part of a Section to the fullest extent
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          Employee Benefit Plans.</font></b> The value of the Award subject to this Agreement shall not be included as compensation, earnings, salaries, or other similar terms used when calculating the Employee&#8217;s benefits under any employee benefit plan
      sponsored by the Company or any Affiliate, except as such plan otherwise expressly provides. The Company expressly reserves its rights to amend, modify, or terminate any of the Company&#8217;s or any Affiliate&#8217;s employee benefit plans.</font></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">7.</font>&#160;</div>
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      This Agreement may not be modified, amended or terminated except by an instrument in writing, signed by you and by a duly authorized representative of the Company. Notwithstanding the foregoing, this Agreement may be amended solely by the Board by a
      writing which specifically states that it is amending this Agreement, so long as a copy of such amendment is delivered to you, and provided that no such amendment adversely affecting your rights hereunder may be made without your written consent.
      Without limiting the foregoing, the Board reserves the right to change, by written notice to you, the provisions of this Agreement in any way it may deem necessary or advisable to carry out the purpose of the grant as a result of any change in
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<DOCUMENT>
<TYPE>EX-10.16
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<FILENAME>exhibit10-16.htm
<DESCRIPTION>EXHIBIT 10.16
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: right"><b>Exhibit 10.16&#160;</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-size: 12pt; font-variant: small-caps"><b>Ionis Pharmaceuticals, Inc.</b></font><br>
    <font style="font-size: 12pt; font-variant: small-caps"><b>Performance Based Restricted Stock Unit Grant Notice</b></font><br>
    <b>(<font style="font-variant: small-caps">2011 Equity Incentive Plan)</font></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">Ionis Pharmaceuticals, Inc. (the <b><i>&#8220;Company&#8221;</i></b>), pursuant to its Amended and Restated 2011 Equity Incentive Plan (the <b><i>&#8220;Plan&#8221;</i></b>), hereby awards to
    Participant a Performance Based Restricted Stock Unit (<b><i>&#8220;PRSU&#8221;</i></b>) Award for the number of stock units set forth below (the <b><i>&#8220;Award&#8221;</i></b>). The Award is subject to all of the terms and conditions as set forth herein; and in the Plan
    and the Performance Based Restricted Stock Unit Agreement (the <b><i>&#8220;Agreement&#8221;</i></b>), both of which are attached hereto and incorporated herein in their entirety. Capitalized terms not otherwise defined herein shall have the meanings set forth in
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        <td>Date of Grant:</td>
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        <td>Target Number of Stock Units Subject to Award:</td>
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        <td>Maximum Number of Stock Units Subject to Award:</td>
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        <td style="text-align: justify; width: 20%"><b>Vesting Schedule</b>: </td>
        <td style="text-align: justify; width: 80%">Subject to Section 4(b) of the Agreement, if Participant ceases to be a Service Provider for any or no reason before Participant vests in the PRSU, the PRSU and Participant&#8217;s right to acquire any shares
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        <td style="text-align: justify; width: 80%">The shares subject to the Award will vest three years following the Date of Grant. The number of shares to vest will be calculated by multiplying the Target Number of shares subject to the Award by a
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        <td style="text-align: justify; width: 80%">You must accept this Award prior to the vest date. If you do not accept this Award by the vest date, this Award will automatically expire.</td>
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        <td style="text-align: justify; width: 20%"><b>Issuance Schedule:</b></td>
        <td style="text-align: justify; width: 80%">The shares of Common Stock to be issued in respect of the Award will be issued in accordance with Section 1 of the Agreement.</td>
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        <td style="text-align: justify; width: 20%"><b>Withholding Right:</b></td>
        <td style="text-align: justify; width: 80%"><i>If permitted by the Company</i>, you may direct the Company (i) to withhold or sell shares in the open market, from shares otherwise issuable in respect of the Award, a portion of those shares with an
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><b>Additional Terms/Acknowledgements:</b> The undersigned Participant acknowledges receipt of, and understands and agrees to, this Grant Notice, the Agreement and the
    Plan. Participant further acknowledges that as of the Date of Grant, this Grant Notice, the Agreement and the Plan set forth the entire understanding between Participant and the Company regarding the Award and supersede all prior oral and written
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        <td><font style="font-variant: small-caps"><b>Participant:</b></font></td>
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      <tr style="vertical-align: top; text-align: left">
        <td>Date:</td>
        <td style="border-bottom: Black 1pt solid">&#160;</td>
        <td>&#160;</td>
        <td>&#160;</td>
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  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0"></td>
        <td style="width: 85.5pt"><font style="font-variant: small-caps"><b>Attachments</b></font>:</td>
        <td style="text-align: left">Performance Based Restricted Stock Unit Agreement</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><b>Ionis Pharmaceuticals, Inc.</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><b>Amended &amp; Restated 2011 Equity Incentive Plan </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><b>Performance Based Restricted Stock Unit Agreement</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Pursuant to the Performance Based Restricted Stock Unit Grant Notice (&#8220;<b><i>Grant Notice</i></b>&#8221;) and this Performance Based Restricted Stock
    Unit Agreement (&#8220;<b><i>Agreement</i></b>&#8221;) and in consideration of your services, Ionis Pharmaceuticals, Inc. (the&#160;&#8220;<b><i>Company</i></b>&#8221;) has awarded you a Performance Based Restricted Stock Unit Award (the &#8220;<b><i>Award</i></b>&#8221;) under its Amended
    &amp; Restated 2011 Equity Incentive Plan (the &#8220;<b><i>Plan</i></b>&#8221;). Your Award is granted to you effective as of the Date of Grant set forth in the Grant Notice for this Award. This Agreement will be deemed to be agreed to by the Company and you upon
    the earlier of (i) signing (or electronic acceptance) by you of the Grant Notice to which it is attached, and (ii) your receipt of shares of Common Stock under this Agreement. Capitalized terms not explicitly defined in this Agreement will have the
    same meanings given to them in the Plan or the Grant Notice, as applicable. In the event of any conflict between the terms in this Agreement and the Plan, the terms of the Plan will control. The details of your Award, in addition to those set forth in
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>1.</b></td>
        <td style="text-align: justify"><font style="font-variant: small-caps"><b>Grant And Vesting of the Award.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>This Award represents the right to be issued
    on a future date the number of shares of the Company&#8217;s Common Stock that is equal to the number of performance based restricted stock units (&#8220;<b><i>PRSUs</i></b>&#8221;) as described below. This Award was granted in consideration of your services to the
    Company. Except as otherwise provided herein, you will not be required to make any payment to the Company (other than past and future services to the Company) with respect to your receipt of the Award, the vesting of the PRSUs or the delivery of the
    Common Stock to be issued in respect of the Award.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>100% of the maximum number of PRSUs subject
    to this Agreement are eligible for vesting at the end of the Performance Period (as defined in Section 2 below) depending on the Company&#8217;s relative Total Shareholder Return at the end of the Performance Period. The PRSUs subject to vesting during the
    Performance Period will be subject to forfeiture and cancellation by the Company if the Company&#8217;s performance during such Performance Period does not meet or exceed the Threshold Level (as defined in the table set forth in Section 3(a)(iii)) of the
    Performance Measure for the Performance Period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Following the end of the Performance Period,
    the Company&#8217;s Compensation Committee (the &#8220;<b><i>Committee</i></b>&#8221;) will certify the Company&#8217;s relative Total Shareholder Return on a percentage rank basis compared to the Comparison Group (the &#8220;<b><i>Performance Measure</i></b>&#8221;) for such Performance
    Period (the &#8220;<b><i>Certification</i></b>&#8221;). Shares underlying vested PRSUs will be promptly distributed following completion of the Certification but in no event later than March 15 of the year following the year in which the applicable Certification
    occurred.</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>2.</b></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-variant: small-caps"><b>Additional Definitions</b></font>.</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>&#8220;<b><i>Comparison Group</i></b>&#8221; means the
    companies included in the NASDAQ Biotechnology Index on the Date of Grant, as may be adjusted as described in Section 3(b)(iii) below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>&#8220;<b><i>Performance Period</i></b>&#8221; means the
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>&#8220;<b><i>Target</i></b>&#8221; means the target
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(d)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>&#8220;<b><i>Total Shareholder Return</i></b>&#8221; or &#8220;<b><i>TSR</i></b>&#8221;
    means total shareholder return as applied to the Company or any company in the Comparison Group, meaning stock price appreciation from the beginning to the end of the Performance Period, plus dividends and distributions made or declared (assuming such
    dividends or distributions are reinvested in the common stock of the Company or any company in the Comparison Group) during the Performance Period, expressed as a percentage return.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>3.</b></td>
        <td style="text-align: justify"><font style="font-variant: small-caps"><b>Calculation</b></font>.</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>For purposes of the Award, the number of
    PRSUs earned at the end of the Performance Period will be calculated using the method as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(i)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>First, for the Company and for
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(ii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Next, rank the TSR values
    determined in step (i) above from low to high (with the company having the lowest TSR being ranked number 1, the company with the second lowest TSR ranked number 2, and so on) and determine the Company&#8217;s percentile rank based upon its position in the
    list by dividing the Company&#8217;s position by the total number of companies (including the Company) in the Comparison Group and rounding the quotient to the nearest hundredth. For example, if the Company was ranked 61 on the list out of 80 companies
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
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    in the right-hand column of the table below corresponding to that percentile rank. Use linear interpolation between points in the table below to determine the percentile rank and the corresponding share funding if the Company&#8217;s percentile rank is
    greater than 25% and less than 90% but not exactly one of the percentile ranks listed in the left-hand column.</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 34%; padding-left: 0.5in">&#160;</td>
        <td style="width: 1%">&#160;</td>
        <td style="width: 32%; text-align: center"><b><u>Relative TSR Percentile Rank</u></b></td>
        <td style="width: 1%">&#160;</td>
        <td style="width: 32%; text-align: center"><b><u>TSR Performance Multiplier</u></b></td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: center">&lt;25<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">0%</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in"><b>Threshold</b></td>
        <td>&#160;</td>
        <td style="text-align: center">25<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">50%</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in"><b>Target</b></td>
        <td>&#160;</td>
        <td style="text-align: center">50<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">100%</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: center">60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">125%</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: center">75<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">150%</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="padding-left: 0.5in"><b>Maximum</b></td>
        <td>&#160;</td>
        <td style="text-align: center">90<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Percentile</td>
        <td>&#160;</td>
        <td style="text-align: center">200%</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.5in; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><i>There is no minimum number of shares or other consideration that you will receive, and no shares will be earned, if the percentile rank is below the 25th
      percentile for the Performance Period.</i></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Rules of Calculation:</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(i)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If the Company&#8217;s absolute TSR is
    negative over the Performance Period, the pay-out will not exceed 100% of Target for the Performance Period, even if the percentile rank exceeds the 50<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> percentile (the &#8220;<b><i>Negative


        TSR Cap</i></b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(ii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160; </font>&#160;&#160;&#160;&#160;</b>Except as modified in
    Section&#160;3(b)(iii) or 3(b)(iv) below, for purposes of computing TSR, the stock price at the beginning of the Performance Period will be the average closing price of a share of common stock over the 20 trading days beginning on the first day of the
    Performance Period, and the stock price at the end of the Performance Period will be the average closing price of a share of common stock over the 20 trading days preceding and including the last day of the Performance Period, adjusted for changes in
    capital structure;&#160;<i>provided, however</i>, that TSR will be negative one hundred percent (-100%) if a company:&#160;(A)&#160;files for bankruptcy, reorganization, or liquidation under any chapter of the U.S. Bankruptcy Code;&#160;(B)&#160;is the subject of an
    involuntary bankruptcy proceeding that is not dismissed within 30 days;&#160;(C)&#160;is the subject of a stockholder approved plan of liquidation or dissolution;&#160;or (D)&#160;ceases to conduct substantial business operations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(iii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Companies will be removed from
    the Comparison Group if they undergo a Specified Corporate Change. A company that is removed from the Comparison Group before the measurement date will not be included at all in the computation of relative TSR. A company in the Comparison Group will be
    deemed to have undergone a <b><i>Specified Corporate Change</i></b><i> if </i>it (A) ceases to be a domestically domiciled publicly traded company on a national stock exchange or market system, unless such cessation of such listing is due to a low
    stock price or low trading volume; (B) has gone private; (C) has reincorporated in a foreign (e.g., non-U.S.) jurisdiction, regardless of whether it is a reporting company in that or another jurisdiction; or (D) has been acquired by another company
    (whether by a peer company or otherwise, but not including internal reorganizations), or has sold all or substantially all of its assets.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(iv)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>The Company&#8217;s Compensation
    Committee may in its good faith discretion calculate the TSRs and TSR Percentile Rank using a subscription service (such as Bloomberg) provided such calculation is (A) consistently applied, (B) intended to ease the burden of administering this Award,
    and (C) intended to preserve the overall intent of this Award.</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>4.</b></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-variant: small-caps"><b>Vesting And Termination of Continuous Service.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>In General</b>. Subject to the limitations
    contained herein, your Award will vest, if at all, in accordance with Section 1 above, provided that vesting will cease upon the termination of your Continuous Service except as set forth below. Upon termination of your Continuous Service, the PRSUs
    that were not vested on the date of such termination will be forfeited at no cost to the Company, and you will have no further right, title or interest in the PRSUs or the shares of Common Stock to be issued in respect of the Award except as set forth
    below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Change in Control</b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(i)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If a Change in Control
    Termination (as such term is defined in the Company&#8217;s Severance Benefit Plan adopted October 18, 2018 (the &#8220;<b><i>Severance Plan</i></b>&#8221;)) occurs during the Change in Control Protection Period (as such term is defined in the Severance Plan), the Award
    will pay-out at Target and the Target PRSUs subject to such Award that have not already vested will vest immediately upon the Change in Control Termination.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(ii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If a Change in Control (as such
    term is defined in the Severance Plan) occurs and your Award will not be assumed, continued or substituted by the successor or acquiror entity in such Change in Control, the Award will pay-out at Target and the Target PRSUs subject to such Award that
    have not already vested will vest immediately upon the Change in Control.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(iii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If a Change in Control (as such
    term is defined in the Severance Plan) occurs and your Award will be assumed, continued or substituted by the successor or acquiror entity in such Change in Control, the PRSUs subject to such Award will automatically convert upon the Change in Control
    to time-vested restricted stock units (&#8220;<b><i>RSUs</i></b>&#8221;) at a rate of one RSU for each of the Target number of PRSUs. The RSUs will not be subject to the relative TSR performance measure described in Section 1 above and instead will vest at Target
    at the end of the applicable Performance Periods outlined in Section 2(b) above that are still remaining at the time of the Change in Control. Such RSUs will be subject to further acceleration in the case of a Change in Control Termination during the
    Change in Control Protection Period (as such term is defined in the Severance Plan).Notwithstanding anything to the contrary in this Agreement or the Severance Plan, if you are a party to a prior written employment agreement, change of control
    agreement, or plan or other similar written agreement or plan (each, a &#8220;<b><i>Prior Agreement</i></b>&#8221;), that provides, in certain circumstances, for greater benefits regarding the accelerated vesting of equity awards (including PRSUs) following a
    Change in Control of the Company or similar transaction, the terms of such Prior Agreement shall control the definition of the term &#8220;<i>Change in Control</i>&#8221; (or any term used therein of similar import) and the terms and conditions by which the
    vesting of the PRSUs may be accelerated as a result of a Change in Control, as well as the benefits that may otherwise be available to you upon a Change in Control.</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">6</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>5.</b></td>
        <td style="text-align: justify"><font style="font-variant: small-caps"><b>Adjustments to Number of Shares</b></font><b>.</b></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b> The number of shares subject to your Award
    may be adjusted from time to time for Capitalization Adjustments, as provided in the Plan.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Any additional shares that become subject to
    the Award pursuant to this Section 5 and Section 9, if any, will be subject, in a manner determined by the Board, to the same forfeiture restrictions, restrictions on transferability, and time and manner of delivery as applicable to the other shares
    covered by your Award.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Notwithstanding the provisions of this
    Section 5, no fractional shares or rights for fractional shares of Common Stock will be created pursuant to this Section 5. The Board will, in its discretion, determine an equivalent benefit for any fractional shares or fractional shares that might be
    created by the adjustments referred to in this Section 5.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>6.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Securities


        Law Compliance</font>.</b> You may not be issued any shares in respect of your Award unless either (i) the shares are registered under the Securities Act; or (ii) the Company has determined that such issuance would be exempt from the registration
    requirements of the Securities Act. Your Award also must comply with other applicable laws and regulations governing the Award, and you will not receive such shares if the Company determines that such receipt would not be in material compliance with
    such laws and regulations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>7.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Transfer


        Restrictions.</font></b> Prior to the time that shares of Common Stock have been delivered to you, you may not transfer, pledge, sell or otherwise dispose of this Award or the shares issuable in respect of your Award, except as expressly provided
    in this Section 7. For example, you may not use shares that may be issued in respect of your Award as security for a loan. The restrictions on transfer set forth herein will lapse upon delivery to you of shares in respect of your vested Award.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Death</b>. Your Award is transferable by will and
    by the laws of descent and distribution. In addition, upon receiving written permission from the Board or its duly authorized designee, you may, by delivering written notice to the Company, in a form provided by or otherwise satisfactory to the Company
    and any broker designated by the Company to effect transactions under the Plan, designate a third party who, in the event of your death, will thereafter be entitled to receive any distribution of Common Stock or other consideration to which you were
    entitled at the time of your death pursuant to this Agreement. In the absence of such a designation, your executor or administrator of your estate will be entitled to receive, on behalf of your estate, such Common Stock or other consideration.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Certain Trusts.</b> Upon receiving written
    permission from the Board or its duly authorized designee, you may transfer your Award to a trust if you are considered to be the sole beneficial owner (determined under Section 671 of the Code and applicable state law) while the Award is held in the
    trust, provided that you and the trustee enter into transfer and other agreements required by the Company.</p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Domestic Relations Orders.</b> Upon receiving
    written permission from the Board or its duly authorized designee, and provided that you and the designated transferee enter into transfer and other agreements required by the Company, you may transfer your Award or your right to receive the
    distribution of Common Stock or other consideration thereunder, pursuant to a domestic relations order that contains the information required by the Company to effectuate the transfer. You are encouraged to discuss the proposed terms of any division of
    this Award with the Company prior to finalizing the domestic relations order to help ensure the required information is contained within the domestic relations order.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><b>8.</b></td>
        <td style="text-align: justify"><font style="font-variant: small-caps"><b>Date of Issuance.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If the Award is exempt from application of
    Section 409A of the Code and the regulations and other guidance thereunder and any state law of similar effect (collectively <b>&#8220;<i>Section 409A</i>&#8221;</b>), the Company will deliver to you a number of shares of the Company&#8217;s Common Stock equal to the
    number of vested PRSUs subject to your Award, including any additional PRSUs received pursuant to Section 5 above that relate to those vested PRSUs in accordance with Section 1(c) above. Notwithstanding the foregoing, in the event that (i) you are
    subject to the Company&#8217;s policy permitting officers and directors to sell shares only during certain &#8220;window&#8221; periods, in effect from time to time (the &#8220;<b><i>Policy</i></b>&#8221;) or you are otherwise prohibited from selling shares of the Company&#8217;s Common
    Stock in the public market and any shares covered by your Award are scheduled to be delivered on a day (the &#8220;<b><i>Original Distribution Date</i></b>&#8221;) that does not occur during an open &#8220;window period&#8221; applicable to you or a day on which you are
    permitted to sell shares of the Company&#8217;s Common Stock pursuant to a written plan that meets the requirements of Rule 10b5-1 under the Exchange Act, in each case as determined by the Company in accordance with the Policy, or does not occur on a date
    when you are otherwise permitted to sell shares of the Company&#8217;s Common Stock on the open market, and (ii) the Company elects not to satisfy its tax withholding obligations (if any) by withholding shares from your distribution, then such shares will
    not be delivered on such Original Distribution Date and will instead be delivered on the first business day of the next occurring open &#8220;window period&#8221; applicable to you pursuant to such policy (regardless of whether you are still providing Continuous
    Services at such time) or the next business day when you are not prohibited from selling shares of the Company&#8217;s Common Stock in the open market, but in no event later than the fifteenth day of the third calendar month of the calendar year following
    the calendar year in which the shares covered by the Award vest. Delivery of the shares pursuant to the provisions of this Section 8(a) is intended to comply with the requirements for the short-term deferral exemption available under Treasury
    Regulation 1.409A-1(b)(4) and will be construed and administered in such manner. The form of such delivery of the shares (<i>e.g.</i>, a stock certificate or electronic entry evidencing such shares) will be determined by the Company.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>The provisions of this Section 8(b) are
    intended to apply if the Award is subject to Section 409A because of the terms of a severance arrangement or other agreement between you and the Company that provides for acceleration of vesting of the Award upon your separation from service (as such
    term is defined in section 409A(a)(2)(A)(i) of the Code and applicable guidance thereunder (&#8220;<b><i>Separation From Service</i></b>&#8221;) and such severance benefit does not satisfy the requirements for an exemption from application of Section 409A provided
    under Treasury Regulations Sections 1.409A-1(b)(4) or 1.409A-1(b)(9) (&#8220;<b><i>Non-Exempt Severance Arrangement</i></b>&#8221;). If the Award is subject to and not exempt from application of Section 409A due to application of a Non-Exempt Severance
    Arrangement, the following provisions in this Section 8(b) will supersede anything to the contrary in Section 8(a).</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">8</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(i)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If the Award vests in ordinary
    course during your Continuous Service in accordance with the vesting schedule set forth in the Grant Notice, in no event will the shares to be issued in respect of your Award be issued any later than the later of: (A) December 31<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">st</sup> of the calendar year that includes the applicable vesting date, or (B) the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that
    follows the applicable vesting date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(ii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If the Award accelerates vesting
    under the terms of your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were in effect as of the Date of Grant of the Award and
    therefore part of the terms of the Award as of the Date of Grant, then the shares will be earlier issued in respect of your Award upon your Separation From Service in accordance with the terms of the Non-Exempt Severance Arrangement, but in no event
    later than the 60<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> day that follows the date of your Separation From Service. However, if at the time the shares would otherwise be issued you are subject to the
    distribution limitations contained in section 409A of the Code applicable to &#8220;specified employees&#8221; as defined in section 409A(a)(2)(B)(i) of the Code and applicable guidance thereunder, such share issuances will not be made before the date which is six
    months following the date of your Separation From Service, or, if earlier, the date of your death that occurs within such six month period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in"><b>(iii)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>If the Award accelerates vesting
    under the terms of your Non-Exempt Severance Arrangement in connection with your Separation From Service, and such vesting acceleration provisions of your Non-Exempt Severance Arrangement were not in effect as of the Date of Grant of the Award and
    therefore not a part of the terms of the Award on the Date of Grant, then such acceleration of vesting of the Award will not accelerate the issuance date of the shares, but the shares will instead be issued on the same schedule as set forth on the
    Grant Notice as if they had vested in ordinary course during your Continuous Service, notwithstanding the vesting acceleration of the Award. Such issuance schedule is intended to satisfy the requirements of payment on a specified date or pursuant to a
    fixed schedule, as provided under Treas. Reg. 1.409A-3(a)(4).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.25in; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>The provisions in this Agreement for delivery
    of the shares in respect of the Award are intended either to comply with the requirements of Section 409A or to provide a basis for exemption from such requirements so that the delivery of the shares will not trigger the additional tax imposed under
    Section 409A, and any ambiguities herein will be so interpreted.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>9.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Dividends.</font></b>
    You will be entitled to receive payments equal to any cash dividends and other distributions paid with respect to a corresponding number of shares to be issued in respect of the PRSUs covered by your Award, provided that if any such dividends or
    distributions are paid in shares, the Fair Market Value of such shares will be converted into additional PRSUs covered by the Award, and further provided that such additional PRSUs will be subject to the same forfeiture restrictions and restrictions on
    transferability as apply to the PRSUs subject to the Award with respect to which they relate.</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">9</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>10.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Restrictive


        Legends.</font></b> The shares issued in respect of your Award will be endorsed with appropriate legends determined by the Company.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>11.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Award not
        a Service Contract</font>.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>Your Continuous Service with the Company or
    an Affiliate is not for any specified term and may be terminated by you or by the Company or an Affiliate at any time, for any reason, with or without cause and with or without notice.&#160; Nothing in this Agreement (including, but not limited to, the
    vesting of your Award pursuant to Section 1 herein or the issuance of the shares in respect of your Award), the Plan or any covenant of good faith and fair dealing that may be found implicit in this Agreement or the Plan will:&#160; (i) confer upon you any
    right to continue in the employ of, or affiliation with, the Company or an Affiliate; (ii) constitute any promise or commitment by the Company or an Affiliate regarding the fact or nature of future positions, future work assignments, future
    compensation or any other term or condition of employment or affiliation; (iii) confer any right or benefit under this Agreement or the Plan unless such right or benefit has specifically accrued under the terms of this Agreement or Plan; or (iv)
    deprive the Company of the right to terminate you at will and without regard to any future vesting opportunity that you may have.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>By accepting this Award, you acknowledge and
    agree that the right to continue vesting in the Award pursuant to Section 1 is earned only by continuing as an employee, director or consultant at the will of the Company (not through the act of being hired, being granted this Award or any other award
    or benefit) and that the Company has the right to reorganize, sell, spin-out or otherwise restructure one or more of its businesses or Affiliates at any time or from time to time, as it deems appropriate (a &#8220;reorganization&#8221;).&#160; You further acknowledge
    and agree that such a reorganization could result in the termination of your Continuous Service, or the termination of Affiliate status of your employer and the loss of benefits available to you under this Agreement, including but not limited to, the
    termination of the right to continue vesting in the Award. You further acknowledge and agree that this Agreement, the Plan, the transactions contemplated hereunder and the vesting schedule set forth herein or any covenant of good faith and fair dealing
    that may be found implicit in any of them do not constitute an express or implied promise of continued engagement as an employee or consultant for the term of this Agreement, for any period, or at all, and will not interfere in any way with your right
    or the Company&#8217;s right to terminate your Continuous Service at any time, with or without cause and with or without notice.</p>
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        Obligations.</font></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>On or before the time you receive a
    distribution of shares subject to your Award, or at any time thereafter as requested by the Company, you hereby authorize any required withholding (if any) from the Common Stock issuable to you and/or otherwise agree to make adequate provision in cash
    for any sums required to satisfy the federal, state, local and foreign tax withholding obligations (if any) of the Company or any Affiliate which arise in connection with your Award (the &#8220;<b><i>Withholding Taxes</i></b>&#8221;). Additionally, the Company
    may, in its sole discretion, satisfy all or any portion of the Withholding Taxes obligation relating to your Award by any of the following means or by a combination of such means: (i) withholding from any compensation otherwise payable to you by the
    Company; (ii) causing you to tender a cash payment; (iii) withholding shares of Common Stock from the shares of Common Stock issued or otherwise issuable to you in connection with the Award with a Fair Market Value (measured as of the date shares of
    Common Stock are issued pursuant to Section 8) equal to the amount of such Withholding Taxes; provided, however, that the number of such shares of Common Stock so withheld will not exceed the amount necessary to satisfy the Company&#8217;s required tax
    withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll taxes, that are applicable to supplemental taxable income; or (iv) selling shares of Common Stock in the open
    market that are issued to you in connection with the Award with a Fair Market Value (measured as of the date shares of Common Stock are issued pursuant to Section 8) equal to the amount of such Withholding Taxes; provided, however, that the number of
    such shares of Common Stock so sold will not exceed the amount necessary to satisfy the Company&#8217;s required tax withholding obligations using the minimum statutory withholding rates for federal, state, local and foreign tax purposes, including payroll
    taxes, that are applicable to supplemental taxable income.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>In the event the Company&#8217;s obligation to
    withhold arises prior to the delivery to you of Common Stock or it is determined after the delivery of Common Stock to you that the amount of the Company&#8217;s withholding obligation was greater than the amount withheld by the Company, you agree to
    indemnify and hold the Company harmless from any failure by the Company to withhold the proper amount.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>13.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Unsecured
        Obligation.</font></b> Your Award is unfunded, and as a holder of a vested Award, you will be considered an unsecured creditor of the Company with respect to the Company&#8217;s obligation, if any, to issue shares pursuant to this Agreement. You will not
    have voting or any other rights as a stockholder of the Company with respect to the shares to be issued pursuant to this Agreement until such shares are issued to you pursuant to Section 8 of this Agreement. Upon such issuance, you will obtain full
    voting and other rights as a stockholder of the Company. Nothing contained in this Agreement, and no action taken pursuant to its provisions, will create or be construed to create a trust of any kind or a fiduciary relationship between you and the
    Company or any other person.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>14.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Other
        Documents</font></b><font style="font-variant: small-caps">.</font> You hereby acknowledge receipt or the right to receive a document providing the information required by Rule 428(b)(1) promulgated under the Securities Act, which includes the Plan
    prospectus. In addition, you acknowledge receipt of the Company&#8217;s insider-trading policy and agree that you may sell shares only in compliance with such policy, in effect from time to time.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>15.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Notices</font>.</b>
    Any notices provided for in your Award or the Plan will be given in writing and will be deemed effectively given upon receipt or, in the case of notices delivered by the Company to you, five days after deposit in the United States mail, postage
    prepaid, addressed to you at the last address you provided to the Company. Notwithstanding the foregoing, the Company may, in its sole discretion, decide to deliver any documents related to participation in the Plan and this Award by electronic means
    or to request your consent to participate in the Plan by electronic means. You hereby consent to receive such documents by electronic delivery and, if requested, to agree to participate in the Plan through an on-line or electronic system established
    and maintained by the Company or another third party designated by the Company.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>16.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Miscellaneous</font>.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(a)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>The rights and obligations of the Company
    under your Award will be transferable to any one or more persons or entities, and all covenants and agreements hereunder will inure to the benefit of, and be enforceable by the Company&#8217;s successors and assigns. Your rights and obligations under your
    Award may only be assigned with the prior written consent of the Company.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(b)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>You agree upon request to execute any further
    documents or instruments necessary or desirable in the sole determination of the Company to carry out the purposes or intent of your Award.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(c)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>You acknowledge and agree that you have
    reviewed your Award in its entirety, have had an opportunity to obtain the advice of counsel prior to executing and accepting your Award, and fully understand all provisions of your Award.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(d)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>This Agreement will be subject to all
    applicable laws, rules, and regulations, and to such approvals by any governmental agencies or national securities exchanges as may be required.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><b>(e)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b>All obligations of the Company under the Plan
    and this Agreement will be binding on any successor to the Company, whether the existence of such successor is the result of a direct or indirect purchase, merger, consolidation, or otherwise, of all or substantially all of the business and/or assets
    of the Company.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>17.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Governing
        Plan Document</font>.</b> Your Award is subject to all the provisions of the Plan, the provisions of which are hereby made a part of your Award, and is further subject to all interpretations, amendments, rules and regulations which may from time to
    time be promulgated and adopted pursuant to the Plan. Except as expressly provided herein, in the event of any conflict between the provisions of your Award and those of the Plan, the provisions of the Plan will control.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>18.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Severability.</font></b>
    If all or any part of this Agreement or the Plan is declared by any court or governmental authority to be unlawful or invalid, such unlawfulness or invalidity will not invalidate any portion of this Agreement or the Plan not declared to be unlawful or
    invalid. Any Section of this Agreement (or part of such a Section) so declared to be unlawful or invalid will, if possible, be construed in a manner which will give effect to the terms of such Section or part of a Section to the fullest extent possible
    while remaining lawful and valid.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>19.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b><b><font style="font-family: Times New Roman, Times, Serif; font-variant: small-caps">Effect on Other Employee Benefit Plans</font>. </b>The value of the Award subject to this Agreement shall not be included as compensation, earnings, salaries, or other similar terms used when
    calculating your benefits under any employee benefit plan sponsored by the Company or any Affiliate, except as such plan otherwise expressly provides. The Company expressly reserves its rights to amend, modify, or terminate any of the Company&#8217;s or any
    Affiliate&#8217;s employee benefit plans.</p>
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    rules.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>21.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="font-variant: small-caps">Amendment.</font></b>
    This Agreement may not be modified, amended or terminated except by an instrument in writing, signed by you and by a duly authorized representative of the Company. Notwithstanding the foregoing, this Agreement may be amended solely by the Board by a
    writing which specifically states that it is amending this Agreement, so long as a copy of such amendment is delivered to you, and provided that no such amendment adversely affecting your rights hereunder may be made without your written consent.
    Without limiting the foregoing, the Board reserves the right to change, by written notice to you, the provisions of this Agreement in any way it may deem necessary or advisable to carry out the purpose of the grant as a result of any change in
    applicable laws or regulations or any future law, regulation, ruling, or judicial decision, provided that any such change will be applicable only to rights relating to that portion of the Award which is then subject to restrictions as provided herein.</p>
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        of the Committee.</font></b> Unless otherwise explicitly provided herein, the Compensation Committee of the Board of Directors of the Company, or an authorized successor committee thereto, shall make all determinations required to be made
    hereunder, including but not limited to determinations relating to the achievement of any thresholds or the vesting of any PRSUs hereunder, and shall interpret all provisions of this PRSU Award Agreement and the underlying PRSUs, as it deems necessary
    or desirable, in its sole and absolute discretion. Such determinations and interpretations shall be binding on and conclusive to the Company and you. Without limiting the foregoing, the Company may, in its sole and absolute discretion, delay payments
    hereunder or make such other modifications with respect to the issuance of stock hereunder as it reasonably deems necessary to the extent that (a) audited financials are not complete for any applicable period during the Performance Period and/or (b)
    the Company has not had an adequate opportunity to review the audited financials or confirm the applicable TSR Percentile Ranks.</p>
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<TYPE>EX-10.23
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<DESCRIPTION>EXHIBIT 10.23
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  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif"><b>Exhibit 10.23</b></font></p>
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      EXHIBIT BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>LEASE AGREEMENT</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">by and between</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>SUDBERRY DEVELOPMENT, INC.,</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">a California corporation,</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">as Landlord</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">and</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>IONIS PHARMACEUTICALS</b>, <b>INC.,</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">a Delaware corporation,</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">Dated as of October 6, 2022</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>TABLE OF CONTENTS</u></font></p>
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      <tr style="vertical-align: top">
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 85%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Page</u></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>1.</b></font></td>
        <td colspan="2" style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>The Premises and Project</b></font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>1</b></font></td>
      </tr>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The Premises; Lease Commencement Date</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The Project</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.3</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.5</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Landlord&#8217;s Warranty</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.</b></font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>3</b></font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Occurrence of Lease Commencement Date</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.3</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Term</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>3.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Renewal Options</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>6</b></font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Extensions</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Determination of Base Rent</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fair Market Rent</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Terms and Conditions</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.5</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Amendment to Lease</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.6</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">No Right During Default</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>4.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Base Rent</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>8</b></font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>5.</b></font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Rent</b></font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>8</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Net Lease</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">General Payment Terms</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">15</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Interest</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">15</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Accord and Satisfaction</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">15</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Late Charge</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">16</font></td>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>6.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Use of Premises</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>16</b></font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Permitted Use</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">16</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Rules</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">17</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Governing Documents</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">17</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Prohibited Uses</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">17</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">i</font>&#160;</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>TABLE OF CONTENTS</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>continued</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 85%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; padding-top: 0; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Page</u></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.5</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Access</font></td>
        <td style="padding-top: 0; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">18</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">24</font></td>
      </tr>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>7.</b></font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>25</b></font></td>
      </tr>
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        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">25</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">25</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.3</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">26</font></td>
      </tr>
      <tr style="vertical-align: top">
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>26</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.1</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">26</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Maintenance by Tenant</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">27</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Utilities</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">28</font></td>
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      <tr style="vertical-align: top">
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        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Insurance; Waiver of Subrogation</b></font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>29</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Landlord&#8217;s Insurance</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">29</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant&#8217;s Insurance</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">30</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.3</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Vendors&#8217; Insurance</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.5</font></td>
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        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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      <tr style="vertical-align: top">
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        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Damages to Premises</b></font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>33</b></font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Repair Estimate</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">33</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant&#8217;s Rights</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">33</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Landlord&#8217;s Rights</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">33</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Repair Obligation</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.5</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Abatement of Rent</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Waiver</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>11.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Condemnation</b></font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>35</b></font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>12.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Assignment and Subletting</b></font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>36</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">No Transfer</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">36</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Requirements for Transfer</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">36</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Conditions to Transfer</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">37</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">No Release</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">38</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.5</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Transfer Premium</font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">38</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>13.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Signs and Fixtures</b></font></td>
        <td style="padding-top: 6pt; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>38</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">ii</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>TABLE OF CONTENTS</u></font> <br>
    <font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>continued</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td colspan="3" style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Page</u></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td colspan="3" style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">13.1 </font></td>
        <td colspan="2" style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Signs</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">38</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt; width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt; width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">13.2 </font></td>
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        <td style="padding-top: 6pt; width: 42%">&#160;</td>
        <td style="text-align: right; padding-top: 6pt; width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">39</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">13.3 </font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Removal</font></td>
        <td colspan="2" style="padding-top: 6pt; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif"><b>Error! Bookmark not defined.</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>14.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Waivers</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>39</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>15.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Quiet Enjoyment and Impairment of Use</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>39</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>16.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Tenant&#8217;s Self-Help Rights</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>39</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>17.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Events of Default; Remedies</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>40</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">40</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">42</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">44</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">17.4 </font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">44</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>18.</b></font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>45</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>19.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Surrender of Premises</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>45</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>20.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Holding Over</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>47</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>21.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Notices</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>47</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>22.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Parking Areas</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>48</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>23.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Brokers</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>48</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>24.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Short Form Lease</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>48</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>25.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Estoppel Certificates</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>48</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>26.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Governing Law, Jurisdiction, and Venue</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>49</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">26.1 </font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Governing Law</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">49</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">26.2 </font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Jurisdiction and Venue</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">49</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>27.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Attorneys&#8217; Fees</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>49</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>28.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>WAIVER OF JURY TRIAL</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>50</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>29.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Interpretation</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>50</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">29.1 </font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Broad Interpretation</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">50</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">29.2 </font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Joint Drafting</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">50</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>30.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Entire Agreement</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>51</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>31.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Counterparts</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>51</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>32.</b></font></td>
        <td colspan="3" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Indemnification</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>51</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32.1 </font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Indemnification by Tenant</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">51</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">iii</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>TABLE OF CONTENTS</u></font> <br>
    <font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>continued</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 306.35pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 85%; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 5%; text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Page</u></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32.2</font></td>
        <td style="padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Procedures for Indemnification of Third-Party Claims</font></td>
        <td style="text-align: right; padding-top: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">51</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Additional Matters</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">53</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Limitations on Liability</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">53</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>33.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>CASp Inspection</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>54</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>34.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Right to Purchase</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>55</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34.1</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Right to Purchase</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">55</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34.2</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Purchase Agreement</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">56</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34.3</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Landlord Right to Sell</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">56</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34.4</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Exclusions</font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">56</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>35.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>OFAC</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>56</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>36.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Financial Information</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>57</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>37.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Severability</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>57</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>38.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>EV Charging Stations</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>57</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>39.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Force Majeure</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>57</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>40.</b></font></td>
        <td colspan="2" style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Roof Equipment</b></font></td>
        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>58</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">58</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">40.2</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">58</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">59</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">40.4</font></td>
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        <td style="text-align: right; padding-top: 6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">59</font></td>
      </tr>
      <tr style="vertical-align: top">
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>LEASE AGREEMENT</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">THIS LEASE AGREEMENT (this &#8220;<b>Lease</b>&#8221;) is made as of October 6, 2022 (the &#8220;<b>Effective Date</b>&#8221;), by and between SUDBERRY DEVELOPMENT, INC.,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">A.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord has the right, subject to certain
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    that certain Amendment No. 2 dated November 6, 2019 (as so amended, the &#8220;<b>Commercial DDA</b>&#8221;) to acquire fee title to that certain vacant, undeveloped real property consisting of approximately 13.1 acres, as reflected on&#160;<u>Exhibit A</u> attached
    hereto&#160;(as may be adjusted pursuant to New Project Documents, the &#8220;<b>Land</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">B.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Upon the satisfaction of certain conditions as set
    forth in the Commercial DDA, Landlord shall acquire fee title to the Land from the City by the recordation of a grant deed (the &#8220;<b>Closing</b>&#8221;) from the City to a-yet-to-be-formed affiliate of Landlord (the &#8220;<b>Landlord Affiliate</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">C.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font> In anticipation of the Closing, Landlord and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">NOW, THEREFORE, in consideration of the foregoing recitals and the mutual covenants contained herein, and for other good and valuable
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>AGREEMENT</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>The Premises; Lease Commencement Date</u>.
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    Tenant each covenant as a material part of the consideration for this Lease to keep and perform each and all of such terms, covenants, and conditions to be kept and performed by it, and that this Lease is made upon the condition of such performance.
    The parties further acknowledge and agree that the purpose of <u>Exhibit A-1</u> is to show the approximate location of the Premises only, and such Exhibit is not meant to constitute an agreement, representation, or warranty as to the construction of
    the Premises, the precise area thereof or the specific location of the Common Areas (as defined below), or the elements thereof or the accessways to the Premises or the Project (as defined below); provided, however, changes to the Project are subject
    to Section&#160;1.4, below. Except as specifically set forth in this Lease and in the Work Letter attached hereto as <u>Exhibit B</u>, Landlord shall tender possession of the Premises to Tenant in its &#8220;<b>AS IS&#8221;</b> condition, and Landlord shall not be
    obligated to provide or pay for any improvement work or services related to the improvement of the Premises or the Project. Landlord shall be deemed to have tendered possession of the Premises to Tenant upon the date of Substantial Completion of
    Landlord&#8217;s Work, as those terms are defined in the Work Letter (the &#8220;<b>Lease Commencement Date</b>&#8221;). Except as expressly set forth in <u>Section&#160;2</u>, below, if for any reason, Landlord is delayed in tendering possession of the Premises to Tenant
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    portion of the Project in accordance with the commonly used or current or revised standards promulgated from time to time by the Building Owners and Managers Association (BOMA) or other generally-accepted measurement standards utilized by Landlord and
    to thereafter adjust the square footage of the Premises, Base Rent (as defined below), and Tenant&#8217;s Proportionate Share (as defined below) of the Project and any other affected tenants of the Building and/or Project and all other future amounts payable
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    Premises are located, as well as (ii) additional land as reflected on <u>Exhibit&#160;A-2</u> attached hereto, upon which improvements for commercial use are intended to be constructed. Tenant acknowledges that Landlord intends to record a final map or
    maps of the Project (the &#8220;<b>Final Map</b>&#8221;) which may, among other things, subdivide all or a portion of the Project, create setbacks or slope areas, road and accessways through the Project, and accomplish other development objectives, but that the
    actual development of the Project, other than Landlord&#8217;s express obligations pursuant to this Lease, is not guaranteed, and that Landlord may or may not construct or include all or any portion of the Project at any time, in its absolute and sole
    discretion. Any Final Map affecting the Premises or Land shall be subject to Tenant&#8217;s approval rights of a New Project Document as set forth in <u>Section 6.3</u>, below. Landlord or a Landlord Affiliate also owns and intends to construct a sports
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    the Project (such areas, together with such other portions of the Project designated by Landlord, in its discretion, are collectively referred to herein as the &#8220;<b>Common Areas</b>&#8221;). The Common Areas shall be maintained and operated by Landlord in a
    manner that is consistent with a first-class mixed-use development.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">1.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord Rights</u>. Subject to the express rights
    and obligations set forth in this Lease, Landlord has the right, in its sole but reasonable discretion, from time to time, to: (a)&#160;make changes to the Project, including, but not limited to, changes in the location, size, shape and number of driveways,
    entrances, parking areas (provided reasonable alternatives acceptable to Tenant are provided), ingress, egress, direction of driveways, entrances and walkways; (b)&#160;close temporarily any portion of the Project for maintenance purposes so long as
    reasonable access to the Premises and parking areas remains available and reasonably convenient as reasonably determined by Tenant; (c)&#160;add additional buildings and improvements to the Project or remove existing buildings or improvements therefrom;
    (d)&#160;use the Common Areas while engaged in making additional improvements, repairs or alterations to the Project or any portion thereof; and (e)&#160;do and perform any other acts, alter or expand, or make any other changes in, to or with respect to the
    Building and/or the Project as Landlord may, in its sole but reasonable discretion, deem appropriate; provided, however, any such changes must be consistent with standards of first-class mixed-use developments. Landlord shall use reasonable efforts
    while conducting any of the foregoing activities to avoid any interference with Tenant&#8217;s use of or access to the Premises, but Landlord shall not be subject to liability nor shall Tenant be entitled to any compensation or abatement or diminution of
    Rent (as defined below) as a result of such activities, Alterations or changes. Notwithstanding anything contained in this Section, or anywhere else in this Lease, at no time shall Landlord (aa)&#160;change the Project in a manner that materially increases
    Tenant&#8217;s obligations or materially reduces Tenant&#8217;s rights under this Lease, including without limitation regarding access to or use of the parking areas, or (bb)&#160; restrict access to the Premises during Tenant&#8217;s normal hours of operation, unless such
    restriction is necessitated by an emergency occurring within or to the Premises, the Building, or the Project.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">1.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Warranty</u>. As of the Lease
    Commencement Date, Landlord shall and hereby does represent and warrant that the Building Systems (as defined below) installed as part of the Landlord&#8217;s Work (as defined in <u>Section 2.1</u> of the Work Letter) shall be in good working order,
    condition, and repair.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>2.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Term; Delays in
        Delivery</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Effectiveness of the Lease</u>. Tenant
    acknowledges that Landlord does not own the Land upon which the Premises are located as of the Effective Date. Notwithstanding the foregoing, subject to the terms and conditions hereof: (i) this Lease shall be and become effective as of the Effective
    Date; provided, however, this Lease shall be and is contingent upon the occurrence of the Closing on or before the Outside Closing Date (as defined below), and (ii) upon the Closing, the conditions set forth in this <u>Section&#160;2.1</u> shall be
    satisfied, and this Lease will be deemed fully effective. Tenant agrees to execute any factually accurate and commercially reasonable amendment to the Lease required by Landlord to memorialize the foregoing and the assignment of the Lease by Landlord
    to the Landlord Affiliate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">2.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Outside Closing Date</u>. Following the
    Effective Date hereof, Landlord shall provide weekly updates on the developments with the City (which may be delivered via e-mail only) and the anticipated date for Closing and shall provide Tenant with written notice of the anticipated date for
    Closing seventy-five (75) days, thirty (30) days and five (5) days in advance thereof. In the event the Closing has not occurred by the date that is eight (8) months after the Effective Date (&#8220;<b>Outside Closing Date</b>&#8221;), Tenant may elect, by written
    notice to Landlord delivered within five (5) days after the Outside Closing Date, to terminate this Lease, in which case neither party shall have any further liability or obligation hereunder, except those liabilities and obligations that expressly
    survive Lease termination; provided, however, that if the Closing has occurred within such five (5)-day period, or if Landlord is able to provide evidence reasonably acceptable to Tenant that the Closing will occur within thirty (30) days, then any
    right to terminate and/or notice thereof shall be deemed rescinded, null and void, and the parties shall continue to be bound by this Lease. In the event the Outside Closing Date does not occur within twelve (12) months after the Effective Date,
    Landlord may elect, by written notice to Tenant delivered within five (5) days after such 12-month period, to terminate this Lease, in which case neither party shall have any further liability or obligation hereunder, except those expressly set forth
    herein. Notwithstanding the foregoing, Landlord shall not have the right to terminate this Lease in the event such delay is caused in whole or in part by the negligence of Landlord, its agents, contractors, employees, or representatives, or anyone
    acting under or on behalf of Landlord. If neither party timely serves the written notice of termination referenced in the preceding sentences, then the Outside Closing Date shall be extended for a period of thirty (30) days, whereupon the rights of the
    parties set forth in the preceding sentence shall again apply with respect to such extended date. The process set forth above shall continue until such time as a party has timely exercised its rights hereunder or the Closing has occurred.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font>&#160;</div>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">2.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Occurrence of Lease Commencement Date</u>.
    Landlord will work diligently and shall use its commercially reasonable, good-faith efforts to cause the Lease Commencement Date to occur on or before the date that is twenty-four (24) months after the point in time at which the City of Oceanside's
    action(s) approving Landlord's Work (the &#8220;<b>Approvals</b>&#8221;) become final either due to (i) the expiration of any appeals/challenge period, with no such appeal or challenge being filed (either through the City of Oceanside or in any court of competent
    jurisdiction) or (ii)&#160;any and all such filed appeal(s) or challenge(s) having been determined, on a final, unappealable basis, as unsuccessful (the &#8220;<b>Estimated Commencement Date</b>&#8221;); provided, however, if no later than five (5) business days prior
    to such Estimated Commencement Date, Landlord delivers evidence reasonably acceptable to Tenant that Landlord is working diligently and continuously and in good faith to complete the Landlord Work and will complete the Landlord Work within thirty (30)
    days, the Estimated Commencement Date shall be extended for such thirty (30) day period. If, for any reason whatsoever, the Lease Commencement Date does not occur on or before the Estimated Commencement Date, this Lease shall not be void or voidable,
    nor shall Landlord, or Landlord&#8217;s agents, advisors, employees, partners, members, shareholders, directors, officers, invitees, independent contractors, or Landlord&#8217;s manager (collectively, &#8220;<b>Landlord Party(ies)</b>&#8221;), be liable to Tenant for any loss
    or damage resulting therefrom except as expressly provided herein. Subject to any contrary provisions in the Work Letter, Tenant shall not be liable for Base Rent until Landlord delivers possession of the Premises to Tenant in the condition required by
    this Lease, and the Lease Expiration Date (as defined below) shall be extended by the same number of days that Tenant&#8217;s possession of the Premises was delayed beyond the Estimated Commencement Date. If the Lease Commencement Date does not occur on or
    before the date that is ninety (90) days after the Estimated Commencement Date (the &#8220;<b>Late Delivery Deadline</b>&#8221;), Landlord will pay Tenant as liquidated damages (and not as a penalty) a late delivery fee in the amount of one (1) day of Base Rent
    for each day of delay after the Late Delivery Deadline that the Lease Commencement Date has not occurred. If the Lease Commencement Date does not occur on or before the date that is sixty (60) days after the Late Delivery Deadline, Tenant shall be
    entitled to two (2) days of Base Rent for each day of delay after the Estimated Delivery Date. If the Lease Commencement Date does not occur on or before the date that is ninety (90) days after the Late Delivery Deadline, Tenant shall have the right to
    terminate this Lease by delivering written notice thereof to Landlord, which termination shall be effective twenty (20) days thereafter if the Lease Commencement Date has not occurred by then. Upon any such termination, Landlord shall return all
    prepaid Rent and the parties shall have no further obligations hereunder, other than such obligations that expressly survive the termination of this Lease. Tenant acknowledges that its rights to late fees and termination as set herein are Tenant&#8217;s sole
    and exclusive remedies at law or in equity for the failure of the Lease Commencement Date and Landlord&#8217;s obligations related thereto to occur as set forth in this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">2.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Delays</u>. Any and all deadlines regarding
    possession and delivery of the Premises, including without limitation, the Estimated Commencement Date, the Lease Commencement Date, the Late Delivery Deadline, and any Key Milestones (as defined below) shall be extended due to Force Majeure (as
    defined below), any Tenant Delays (as defined in <u>Section 2.4.1</u> of the Work Letter), and any delay or delays encountered by Landlord affecting the construction of Landlord&#8217;s Work (as defined below) solely due to waiting periods for obtaining
    governmental permits or approvals in excess of the time periods normally required to obtain such permits or approvals for newly-constructed, similarly-improved office and laboratory buildings in San Diego, California provided Landlord is diligently and
    continuously pursuing such approvals and permits. Landlord shall provide Tenant with regular updates regarding the progress of the Landlord&#8217;s Work, the Estimated Commencement Date, the anticipated date of Substantial Completion of Landlord&#8217;s Work, and
    any significant changes to the construction schedule. Notwithstanding the foregoing and anything herein to the contrary, in the event Landlord fails to achieve any of the following, Tenant shall have the right, as its sole remedy, to terminate this
    Lease, and neither party shall thereafter have any further rights or obligations under this Lease except those which expressly survive such termination: (a)&#160;Landlord does not obtain all Approvals by June 30, 2023 provided that if any appeal of or
    challenge to an Approval is filed, such date shall be tolled until the determination of such appeal or challenge, on a final, unappealable basis, as unsuccessful; (b)&#160;Landlord fails to commence grading of the Land upon which the Premises will be
    located on or before July 31, 2023, or (c) Landlord fails to commence active construction on site of Landlord&#8217;s Work by March 15, 2024 (each of the foregoing, a &#8220;<b>Key Milestone</b>&#8221;). In the event Landlord fails to achieve a Key Milestone, Tenant may
    provide Landlord with written notice within thirty (30) days following the expiration of the Key Milestone of its election to terminate the Lease (&#8220;<b>Notice</b>&#8221;); such Notice shall become effective thirty (30) days after delivery thereof if Landlord
    does not achieve the applicable Key Milestone within such 30-day period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">2.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Term</u>. The term of this Lease (the &#8220;<b>Term</b>&#8221;)







    shall commence on the Lease Commencement Date. If the Lease Commencement Date occurs on the first day of a calendar month, the lease expiration date shall be the day immediately preceding the twenty (20) year, three&#160;(3) month anniversary of the Lease
    Commencement Date; or if the Lease Commencement Date shall be other than the first day of a calendar month, the Lease expiration date shall be the last day of the month in which the twenty (20) year, three (3) month anniversary of the Lease
    Commencement Date occurs (as the case may be, the &#8220;<b>Lease Expiration Date</b>&#8221;), or such earlier date as this Lease may otherwise terminate in accordance with its terms, covenants, conditions, and provisions. The lease year (&#8220;<b>Lease Year</b>&#8221;)
    means the twelve (12)-month period commencing on the first day of the first calendar month following the Lease Commencement Date (unless the Lease Commencement Date is the first day of the calendar month, in which case the first Lease Year shall
    commence on the Lease Commencement Date) and each consecutive period of twelve&#160;(12) calendar months thereafter during the Term. The initial Term may be extended by Tenant exercising the renewal options pursuant to&#160;<u>Section&#160;3</u>, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5</font>&#160;</div>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>3.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Renewal Options</u></b>.
    Tenant shall have the right to extend the Term of the Lease upon the following terms and conditions:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Extensions</u>. Tenant has, subject to the
    provisions of this <u>Section 3</u>, the right (&#8220;<b>Option to Extend</b>&#8221;) to extend the Term for two (2) additional term(s) of ten (10) years each (each, an &#8220;<b>Extension Term</b>&#8221;) commencing on the day following the expiration of the Term (each, a
    &#8220;<b>Commencement Date of the Extension Term</b>&#8221;). Tenant will give Landlord written notice (the &#8220;<b>Extension Notice</b>&#8221;) of Tenant&#8217;s election to extend the Term no more than twenty-four (24) months and at least eighteen (18) months prior to the
    scheduled expiration of the Term (the &#8220;<b>Extension Notice Deadline</b>&#8221;). Such notice will constitute Tenant&#8217;s irrevocable election to extend the Term and may not subsequently be revoked by Tenant. Time is of the essence with respect to the timing of
    such requirement to give notice to Landlord. Each Option to Extend the Term is personal to the Tenant originally named in the Lease and may not be exercised by any assignee or subtenant except as a result of a Permitted Transfer (as defined below).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Determination of Base Rent</u>. The Base Rent
    starting on the Commencement Date of the Extension Term and continuing for twelve (12) months thereafter will be one hundred percent (100%) of the then-prevailing market rate for new leases for comparable life sciences manufacturing space to the
    Premises in comparable buildings to the Building in the State of California that a willing, comparable, non-equity tenant (excluding sublease and assignment transactions) would pay, and a willing, comparable landlord of life sciences manufacturing
    space would accept, at arm&#8217;s length (&#8220;<b>Fair Market Rent</b>&#8221;); provided that, in no event shall the Fair Market Rent on the Commencement Date of the first Extension Term be less than the Base Rent on the last day of the 15th year of the Term, and in
    no event shall the Fair Market Rent on the Commencement Date of the second Extension Term be less than the Base Rent on the last day of the 20th year of the Term. Thereafter, the Base Rent shall be increased by three percent (3%) on each annual
    anniversary of the applicable Commencement Date of the Extension Term. Fair Market Rent will reflect all monetary and non-monetary considerations for comparable transactions, including the age, quality and layout of the existing improvements in the
    Premises, brokerage commissions, improvements paid for by Tenant improvement allowances, moving allowances, and rent concessions. Fair Market Rent will be adjusted to consider the size of the Premises, the length of the Extension Term, and the credit
    of Tenant, but will be calculated without taking into account any improvements paid for by Tenant pursuant to this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Fair Market Rent</u>. Landlord will notify Tenant
    of its determination of the Fair Market Rent (consistent with the methodology reflected in <u>Section 3.2</u>, above) for the applicable Extension Term no later than thirty (30) days after Tenant delivers an Extension Notice. If Tenant delivers
    written notice to Landlord within thirty (30) days after its receipt of Landlord&#8217;s determination of Fair Market Rent whereby Tenant disagrees with Landlord&#8217;s determination of the Fair Market Rent, Landlord and Tenant will diligently and in good faith
    confer for a period of thirty (30) days thereafter in an attempt to agree on the Fair Market Rent. In the event Landlord and Tenant fail to reach an agreement on the Fair Market Rent within such thirty (30)-day period, then the Fair Market Rent that
    will be used in computing Base Rent for the applicable Extension Term will be determined as follows: within five (5) business days after the expiration of the thirty&#160;(30)-day period described above, Landlord and Tenant will each select an independent
    appraiser with at least ten (10) years&#8217; experience in the San Diego market. The two (2) appraisers will exchange their respective determinations of Fair Market Rent within ten (10) days after their selection, and if the lower appraisal is not less than
    ninety-five percent (95%) of the higher appraisal, then the two (2) appraisals will be averaged, and the result will be the Fair Market Rent. If, however, the two (2) appraisers are unable to agree on the Fair Market Rent or the lower appraisal is less
    than ninety-five percent (95%) of the higher appraisal, they then will select a similarly-qualified third appraiser (the &#8220;<b>Neutral Appraiser</b>&#8221;). Within five (5) days after selection of the Neutral Appraiser, each of Landlord&#8217;s appraiser and
    Tenant&#8217;s appraiser will provide the Neutral Appraiser with their respective determinations of Fair Market Rent, and the Neutral Appraiser&#8217;s only role shall be to select, within fifteen (15) days thereafter, which of the two submitted determinations is
    closer to Fair Market Rent in such Neutral Appraiser&#8217;s discretion. Each party will pay the cost of its own appraiser and the parties will share the cost of the Neutral Appraiser equally. If the process described in this <u>Section&#160;3</u> has not
    resulted in a determination of Fair Market Rent by the commencement of the applicable Extension Term, then the existing Base Rent will be used until the appraiser(s) reach a decision, with an appropriate rental credit and other adjustments to be made
    by the parties as necessary once the determination of Fair Market Rent has been made.</p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">6</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Terms and Conditions</u>. Except for the Base Rent
    as determined above, Tenant&#8217;s occupancy of the Premises during the applicable Extension Term will be on the same terms and conditions as are in effect immediately prior to the expiration of the Term; provided that Tenant will have no further options to
    extend this Lease once all options set forth in this <u>Section 3</u> have been exercised, no Allowance (as defined in <u>Section 6</u> of the Work Letter) shall be applicable, and Landlord shall have no obligations to improve the Premises or make
    any contributions toward improvement of the Premises in any manner whatsoever.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Amendment to Lease</u>. If this Lease is extended
    for an Extension Term, then Landlord will prepare an amendment to this Lease confirming the extension of the Term and the other provisions applicable thereto and Landlord and Tenant will execute the amendment within thirty (30) days after agreement on
    the final form of such amendment, provided that any such extension will be effective irrespective of the execution of any such amendment. If Tenant exercises its right to extend the Term for an Extension Term, the Term as used in this Lease will be
    construed to include the applicable Extension Term.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Right During Default</u>. Tenant shall not have
    the right to extend the Term, notwithstanding anything set forth above to the contrary: (a) during any period of time commencing from the date Landlord gives written notice to Tenant that Tenant is in a monetary or material non-monetary default under
    any provision of the Lease, and continuing until the default alleged in said notice is cured; or (b)&#160;in the event that Landlord has given to Tenant two or more notices of default for the same monetary or material non-monetary default or three or more
    late charges have become payable under the Lease during the twelve (12)-month period prior to the time that Tenant intends to exercise an Option to Extend. The period of time within which an Option to Extend may be exercised shall not be extended or
    enlarged by reason of Tenant&#8217;s inability to exercise such Option to Extend (with the exception of an event of Force Majeure) because of the foregoing provisions of this Section, even if the effect thereof is to eliminate Tenant&#8217;s right to exercise such
    Option to Extend.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>4.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Base Rent</u></b>.
    Commencing on the date that is ninety (90) days after the Lease Commencement Date (the &#8220;<b>Rent Commencement Date</b>&#8221;), Tenant will pay to Landlord, in advance without set-off, deduction, prior notice or demand, one-twelfth (1/12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>) of the Annual Base Rent (the &#8220;<b>Base Rent</b>&#8221;) on or before the first calendar day of each month. Notwithstanding the foregoing, the Base Rent for the first full month
    of the Term shall be due and payable upon the commencement of construction of the Landlord&#8217;s Work. If the Rent Commencement Date is other than the first day of the month, Base Rent shall be pro-rated for the fraction of the month in which the Rent
    Commencement Date occurs in accordance with&#160;<u>Section&#160;5.2</u>, below, and shall be due concurrently with the Base Rent due for the second month of the Term. Annual base rent (&#8220;<b>Annual Base Rent</b>&#8221;) for the first twelve (12) months of the Term is
    defined as the amount that is equal to 7.9% of the Actual Costs (as defined in <u>Section&#160;7.2</u> of the Work Letter). Base Rent shall increase on each annual anniversary of the Rent Commencement Date (each, a &#8220;<b>Base Rent Adjustment Date</b>&#8221;)
    during the Term, to equal one hundred three percent (103%) of the Base Rent in effect immediately prior to the applicable Base Rent Adjustment Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>5.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Rent</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">5.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Net Lease</u>. &#8220;<b>Additional Rent</b>&#8221; shall mean
    all sums (exclusive of Base Rent) that Tenant is required to pay to Landlord under this Lease. <font style="font-family: Times New Roman, Times, Serif">The Base Rent, and the Additional Rent shall be collectively referred to as the </font>&#8220;<b>Rent.</b><font style="font-family: Times New Roman, Times, Serif">&#8221; </font>This is a net lease and the Rent and all other sums payable hereunder by Tenant shall be paid without notice (except as expressly provided herein), demand, setoff, counterclaim, abatement,
    suspension, deduction, or defense. &#8220;<b>Tenant&#8217;s Proportionate Share</b>&#8221; means one hundred percent (100%) of the Building and Tenant's Proportionate Share of the Project, based on Landlord&#8217;s good faith estimates of the improvements to be constructed on
    the Project but subject to actual construction, measurement, and remeasurement as set forth in <u>Section&#160;1.1.1</u> above, and the Final Map, is 36.08%. Tenant acknowledges that the Building is part of a multi-building project and that certain costs
    and expenses incurred in connection with the Project shall be shared between the Building and the other buildings in the Project. As such, Landlord shall have the right, from time to time, to equitably allocate some or all of such expenses among
    different portions or occupants of the Project, in Landlord&#8217;s reasonable discretion. Without limiting the foregoing:</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">5.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Taxes</u>. Landlord pays all Taxes (as defined
    below) levied or assessed against the Premises which are applicable to the Term, and Tenant&#8217;s Proportionate Share of Taxes will be included in the Operating Expenses charged to Tenant. &#8220;<b>Taxes</b>&#8221; shall mean all federal, state, county, or local
    government or municipal taxes, fees, charges, or other impositions of every kind or nature, whether general, special, ordinary, or extraordinary, now or in the future, which are assessed, levied, charged, or imposed: (A) on the Project or any part
    thereof; (B) on Landlord with respect to the Project; (C) on the act of entering into this Lease; (D)&#160;on the use or occupancy of the Project or any part thereof; (E) with respect to services or utilities consumed in the use, occupancy, or operation of
    the Project; (F) on or attributable to personal property used in connection with the Project; (G)&#160;related to any transportation plan, fund, or system affecting the Project; and (H) relating to or on or measured by the Rent payable under this Lease, and
    any other tax, fee, or other excise, however described, which may be levied or assessed in lieu of, as a substitute (in whole or in part) for, or as an addition to, any of the foregoing. Taxes include taxes, fees, and charges such as real property
    taxes, general and special assessments, transit taxes, leasehold taxes, and taxes based on the receipt of Rent (including gross receipts or sales taxes applicable to the receipt of Rent, unless required to be paid by Landlord), and personal property
    taxes imposed on Landlord&#8217;s fixtures, machinery, equipment, apparatus, systems, appurtenances, and other personal property used in connection with the Project, along with reasonable legal and other professional fees, costs and disbursements incurred in
    connection with proceedings to contest, determine or reduce real property taxes. Notwithstanding the foregoing, the following shall be excluded from Taxes: (i) any capital gains, capital levy, franchise, estate, inheritance, gift, corporation or
    unincorporated business, excise, income, profit, transfer or recordation, license fee, capital stock, net or excess profits, the ballpark tax and similar taxes which are assessed at the entity level against both Landlord and Tenant, as well as any
    abatements, reductions or credits received by Landlord in connection with the foregoing, (ii) those taxes which are directly associated with the process of construction of the Building (as opposed to taxes on the improvements), (iii) any fines,
    penalties and interest on late payments; provided, however, that if the taxing authority permits a taxpayer to elect to pay in installments, Landlord shall be permitted to pay such Taxes in installments and the interest charges resulting therefrom
    shall be deemed and included within Taxes, (iv) any expenses if included in Operating Expenses, and (vi) any taxes levied against the Project prior to the Lease Commencement Date, and (vii) taxes based on increases in assessed value due to any of the
    following actions, except to the extent the costs of such actions are permitted as Operating Expenses pursuant to <u>Section 5.1.3</u>, below: (a) any mortgaging or refinancing of the Project; (b) improvements for other occupants of the Project; and
    (c) capital improvements to the Project which do not benefit Tenant. Real estate taxes for the year in which the Lease Commencement Date occurs will be prorated as to Tenant and Landlord based on the number of days of occupancy as related to three
    hundred sixty-five (365) days.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">5.1.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font><u>Taxes Appeal Rights</u>. In the event that, following
    receipt of written notice from Tenant requesting that Landlord pursue an appeal, protest or contest of property Taxes relating to the Premises or Building, Landlord elects not to pursue, or fails to commence such appeal, protest or contest prior to the
    earlier of (i) sixty (60) days after receipt of such notice and (ii) the date that is five (5) business days prior to the date such appeal, protest or contest is due, Tenant, at its sole cost and expense, shall have the right to pursue an appeal,
    protest or contest of such property Taxes in the name of Landlord; provided that Tenant notifies Landlord not less than seven (7) business days in advance that it is in fact pursuing such an appeal, protest or contest. Landlord, at no out-of-pocket
    cost and expense or liability to Landlord, shall reasonably cooperate with any such appeal, protest or contest, including without limitation by promptly executing any filings, authorizations, documents or other instruments reasonably required for
    Tenant to pursue in good faith such appeal, protest or contest; provided, however, in no event shall Tenant settle any such dispute without obtaining Landlord&#8217;s prior reasonable approval with respect thereto, which Landlord shall provide (or if
    disapproving, provide the disapproval with a reasonably-detailed explanation for the disapproval) within five (5) business days following receipt thereof. If Landlord (or Tenant in the name of Landlord) so contests the Taxes or assessment and such
    contest results in a refund of any portion of real estate taxes that were included in the Taxes paid by Tenant, then Landlord shall credit against the next estimated payment or payments due as Additional Rent an amount equal to Tenant&#8217;s Proportionate
    Share of the refunded Taxes or if the Term has expired, Landlord shall refund such amount to Tenant within thirty (30) days after Landlord&#8217;s receipt thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">5.1.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font><u>Personal Property Taxes</u>. Tenant shall pay, prior
    to delinquency, any and all Taxes levied or assessed against any Tenant&#8217;s Property (as defined below), whether levied or assessed against Landlord or Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">5.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Utilities</u>. Tenant shall cause all utilities
    to be placed in its name and shall pay the actual costs for all utilities, including without limitation, water, sewer, natural gas, telephone, and electricity, used on the Premises. Tenant&#8217;s obligation to pay utilities for periods during the Term shall
    survive the expiration or earlier termination of this Lease.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">5.1.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Operating Expenses</u>. In addition to Base Rent
    payable by Tenant pursuant to <u>Section 4</u>, above, on the first day of each calendar month beginning after the Lease Commencement Date, Tenant shall pay to Landlord, as Rent, without notice, demand, offset, or deduction, one-twelfth of all
    Operating Expenses for the calendar year in which the Lease Commencement Date occurs, and for each calendar year thereafter during the Term, as estimated by Landlord in the most recently-delivered Estimated Statement (as defined below). Landlord shall
    deliver to Tenant, prior to the commencement of the Lease Commencement Date and prior to each anniversary of the Lease Commencement Date thereafter, a written statement (&#8220;<b>Estimated Statement</b>&#8221;) setting forth Landlord&#8217;s estimate of the Operating
    Expenses allocable to the ensuing calendar year (or portion thereof). Landlord may, at its option, during any such year (but no more than twice in any one calendar year), deliver to Tenant a revised Estimated Statement, revising Landlord&#8217;s estimate of
    the Operating Expenses in accordance with Landlord&#8217;s most current estimate. No later than one hundred twenty (120) days after the end of each calendar year during the Term, Landlord shall deliver to Tenant a written statement (&#8220;<b>Actual Statement</b>&#8221;)







    setting forth the actual Operating Expenses allocable to such calendar year. Tenant&#8217;s failure to object to Landlord regarding the contents of an Actual Statement, in writing, within one hundred twenty (120) days after delivery to Tenant of such Actual
    Statement shall constitute Tenant&#8217;s absolute and final acceptance and approval of the Actual Statement, except in the event Tenant is later able to prove fraud or intentional misrepresentation. Following Landlord&#8217;s receipt of Tenant&#8217;s written request,
    Landlord shall also provide Tenant with reasonable back-up information (e.g., tax bills, bills for utility costs, etc.) as well as explanations based on known costs and reasonable projections. If the sum of Tenant&#8217;s monthly payments actually paid by
    Tenant during any calendar year exceeds Tenant&#8217;s obligations for Operating Expenses allocable to such year as reflected in an Actual Statement, then such excess will be credited against Tenant&#8217;s future monthly payments of Operating Expenses, unless
    such year was the year during which the Term expires or is terminated (the &#8220;<b>Last Calendar Year</b>&#8221;), in which event either (i) such excess shall be credited against any monetary default or outstanding obligation of Tenant under this Lease, or (ii)
    if Tenant is not in default under this Lease and has no outstanding monetary obligations at such time, then Landlord shall pay to Tenant such excess within thirty (30) days after the expiration or termination of the Term. If the sum of Tenant&#8217;s monthly
    payments of Operating Expenses actually paid by Tenant during any calendar year is less than Tenant&#8217;s Proportionate Share of the actual Operating Expenses allocable to such year, then Tenant shall, within thirty (30) days of delivery of the Actual
    Statement, pay to Landlord the amount of such deficiency. The references in this Section to the actual Operating Expenses allocable to a calendar year shall include, if such calendar year is the Last Calendar Year, the actual Operating Expenses
    allocable to the portion of such year prior to the expiration or termination of the Term, calculated on a pro rata basis, without regard to the date of a particular expenditure. The provisions of this Section shall survive the termination of this
    Lease, and even though the Term has expired, and Tenant has vacated the Premises, when the final determination is made of Operating Expenses for the year in which this Lease terminates, which shall be within one hundred twenty (120) days after the end
    of such year, Tenant shall promptly pay any increase due over the estimated expenses paid by Tenant pursuant hereto and conversely any overpayment made in Tenant&#8217;s estimated payments shall be promptly rebated by Landlord to Tenant. Notwithstanding the
    foregoing, if Landlord fails to provide the Actual Statement within thirty (30) days after written notice from Tenant that Landlord did not deliver the Actual Statement by the applicable date set forth herein, Landlord shall not have the right to
    collect from Tenant any underpayment of Tenant&#8217;s Proportionate Share of Operating Expenses that may be determined for the period covered by such Actual Statement. Landlord shall not recover more than one hundred percent (100%) of the Operating Expenses
    actually incurred by Landlord and in the event that Landlord shall collect more than one hundred percent (100%), Landlord shall promptly reimburse to Tenant, Tenant&#8217;s Proportionate Share of any such excess to the extent paid by Tenant.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">5.1.3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font><u>Definition of Operating Expenses</u>. Subject to the
    Excluded Costs (as defined below), the term operating expenses (&#8220;<b>Operating Expenses</b>&#8221;) means all reasonable expenses, costs, and amounts of every kind or nature that Landlord pays or incurs because of or in connection with (but only to the extent
    applicable to) the ownership, operation, management, maintenance, or repair of the Project. Operating Expenses include, without limitation, the following amounts paid or incurred relative to the Project: (a) the cost of operating, managing,
    maintaining, and repairing all systems, including without limitation utility, mechanical, sanitary and storm drainage systems, and the cost of supplies, tools, and equipment, as well as commercially-reasonable maintenance and service contracts in
    connection with those systems, (b)&#160;the costs of licenses, certificates, permits, and inspections relating to the operation of the Project, including without limitation, costs related to any transportation management development plan for the Project if
    included in the Governing Documents (as defined below) and subject to the provisions of <u>Section 5</u>, (c)&#160;the costs of contesting the validity or applicability of any government enactments that may affect the Premises, the Project, or Operating
    Expenses, (d) fees, charges, and other costs, including administrative fees, management fees, and accounting costs, consulting fees, legal fees, and accounting fees of all persons engaged by Landlord or otherwise reasonably incurred by Landlord in
    connection with the operation, management, maintenance, and repair of the Premises; provided, however such management fee shall not exceed one percent (1%) of the net rent of the Project, subject to <u>Section 8.2.4</u>, below, (e) any costs or
    expenses payable pursuant to any declaration of covenants, conditions, and restrictions, reciprocal easement and/or maintenance agreement, conditions of approval, or similar instrument recorded against the Project, either now or in the future,
    including any association or similar fees, assessments or dues presently or hereafter established and applicable to the Project (collectively, the &#8220;<b>Governing Documents</b>&#8221;), subject to the terms set forth below, (f)&#160;amortization (including interest
    on the unamortized cost at a rate equal to the floating commercial loan rate announced from time to time by Bank of America as its &#8220;<b>Prime Rate</b>&#8221; (or a comparable rate selected by Landlord if such Prime Rate ceases to be published) plus one (1)
    percentage point per annum of the cost of acquiring or renting personal property used in the maintenance, repair, and operation of the Project, (g) Taxes, (h) the cost of capital improvements which (1) are intended as a labor saving or cost saving
    device or to effect other economies in, or otherwise improve, the maintenance or operation of the Project, or (2) are required under any government law or regulation enacted after the Effective Date, but only to the minimum extent required, (i) all
    costs of insurance to be maintained by Landlord pursuant to <u>Section 9</u>, below, (j)&#160;environmental management fees and environmental audits, (k) all recurring costs to satisfy any conditions of approval of the Project to the extent included in the
    Governing Documents, conditions imposed upon the Project, and/or to comply with applicable municipal, state and federal laws, statutes, codes, rules, regulations, ordinances, requirements, and orders (collectively, &#8220;<b>Laws</b>&#8221;), now in force or which
    may hereafter be in force, including without limitation, any stormwater treatment requirements, water quality requirements, or transportation demand management program, all as subject to the terms set forth below and (l)&#160;the costs of applying for,
    obtaining, maintaining, managing, and reporting associated with: (A)&#160;energy efficiency; energy measurement and reporting; water usage; recycling, composting, and waste management; indoor air quality; and chemical use (collectively, the &#8220;<b>Sustainability







      Practices</b>&#8221;), or (B) the U.S. EPA&#8217;s Energy Star&#174; Portfolio Manager, the Green Building Initiative&#8217;s Green Globes&#8482; building rating system, the U.S. Green Building Council&#8217;s Leadership in Energy and Environmental Design (LEED&#174;) building rating
    system, the <font style="text-transform: uppercase">Ashrae </font>Building Energy Quotient (BEQ), the Global Real Estate Sustainability Benchmark (GRESB), or other standard for high performance buildings adopted by Landlord with respect to the
    Building, as the same may be revised from time to time (as the case may be, the &#8220;<b>Green Building Standards</b>&#8221;); provided, however, such costs for Sustainability Practices or Green Building Standards included in Operating Expenses for any calendar
    year shall not increase by more than three percent (3%) per calendar year on a straight line basis. All capital expenditures permitted pursuant to clause (1) and clause (2) of subparagraph (h) above shall be amortized (including interest on the
    unamortized cost at the rate stated in subparagraph (f) of this Section) over their useful life, as reasonably determined by Landlord in accordance with sound accounting principles consistently applied. Notwithstanding the foregoing, Operating Expenses
    shall be net of any discounts, credits, reimbursements, and rebates received by Landlord for Operating Expenses.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">5.1.3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font><u>Definition of Excluded Costs</u>. &#8220;<b>Excluded Costs</b>&#8221;
    means the following expenses: (1) depreciation, principal, interest, and fees on mortgages; (2) real estate brokers&#8217; leasing commissions and marketing, advertising and promotional costs and expenses incurred in connection with the marketing of the
    Project, Building or any rentable space therein; (3) costs of any items to the extent Landlord actually receives reimbursement therefor from insurance proceeds, any tenant, occupant, or third party, or under warranties (such costs shall be excluded or
    deducted&#8212;as appropriate&#8212;from Operating Expenses in the year in which the reimbursement is received); (4)&#160;costs, including fines, penalties, and legal fees incurred, due to violations by any Landlord Party of applicable Laws, contracts, or leases
    pertaining to the Project, or title matters; (5) costs incurred or repairs necessitated by the gross negligence or willful misconduct of Landlord; (6) capital expenses other than those specifically included in the definitions of Operating Expenses; (7)
    charitable or political contributions and membership fees or other payments to trade organizations; (8) Landlord&#8217;s general overhead expenses not related to the Project; (9) overhead and profit paid to subsidiaries or any Landlord Affiliate for
    management or other services, or for supplies or other materials, to the extent the amounts incurred exceed those that would have been reasonably incurred if such supplies, materials, or services were obtained from unrelated third parties; (10) wages,
    salaries, and other compensation paid to personnel above the grade of property manager; (11) cost of insurance coverages not generally carried by landlords of similar premises in the area, provided that the parties agree the cost of the coverages
    carried by Landlord as of the Lease Commencement Date shall be included as part of Operating Expenses; (12) costs and expenses incurred in leasing equipment or systems that would ordinarily constitute a capital expenditure if such equipment or systems
    were purchased, to the extent such rental charges exceed the amortization charge, if any, that would have been permitted had the item been purchased; (13) management fees in excess of what is permitted by <u>Section 5.1.3.1(d)</u>, above;
    (14)&#160;interest and amortization of mortgages or any other funds borrowed by Landlord; (15) base ground rent plus escalations; (16) income, excess profit, franchise taxes or other such taxes imposed on or measured by the gross or net income of Landlord
    from the operation of the Building; (17) rent (actual or implied) and expenses for management office(s) located at the Project; (18)&#160;all costs and expenses incurred by Tenant or any other tenants of the Building and paid for or payable directly by
    Tenant or such other tenants either to third parties or to Landlord under agreements for direct payment or reimbursement for benefits or services; (19) costs incurred to remove, remediate, or otherwise arising from the presence of any Hazardous
    Materials (as defined below) or other toxic material or substances from or at either the Building, the Project or Premises in violation of Laws, and any costs incurred in connection with any governmental investigation, order, proceeding or report with
    respect thereto; (20) costs, including overhead and general administrative expenses, relating to the operation of the business of the legal entity or entities which constitute Landlord, either as a corporation, partnership, trust or other entity, such
    as trustee&#8217;s fees, annual fees, partnership expenses, and legal, professional, consulting, and accounting fees (other than with respect to Building operations), including without limitation, sale and financing matters, legal entity accounting, income
    taxation matters and disputes with employees or persons who own an interest in Landlord, and costs and expenses relating to maintaining Landlord&#8217;s existence, such as trustee&#8217;s fees, annual fees, partnership expenses, administrative fees, deed
    recordation and legal and accounting fees relating to maintaining such existence; (21) funding reserves; (22) attorneys&#8217; fees, costs, disbursements and other expenses incurred in connection with negotiations or disputes with, or leasing to, tenants or
    prospective tenants of the Building; (23) costs for acquisition and initial construction of the Building or Project or in a tenant&#8217;s premises specifically for a tenant&#8217;s occupancy; (24) any expenses for repairs or maintenance which are recovered or
    recoverable under warranties and service contracts; (25) costs incurred as a result of the violation by Landlord or other tenants of the Building or the Project of the terms and conditions of any lease (including indemnity costs incurred by Landlord
    due a violation of such lease caused solely by Landlord&#8217;s actions or inactions) or other agreement with Landlord as a party; (26) the costs of any &#8220;tap fees&#8221; or condenser water loop, sewer or water connection fees for the Building payable in connection
    with the initial construction of the Building or the Premises; (27) costs of repairing, replacing or otherwise correcting a physical defect (but not the costs of normal repair and maintenance) or design defect in the initial construction by Landlord of
    the Building (including, without limitation, the Building roof, the foundation, structure and curtain wall); (28) costs of Landlord&#8217;s Work; (29)&#160;costs allocated to buildings other than the Building in which Landlord or any Landlord Affiliate has a
    direct or indirect interest; (30) costs of any additions to the Building or Project; (31)&#160;costs of purchasing artwork, sculptures or paintings; (32) allowances, concessions, permits, licenses, inspections and other costs and expenses incurred in
    completing, fixturing, furnishing, renovating or otherwise improving, decorating or redecorating space for Tenant or other tenants or prospective tenants of the Building, including, without limitation, constructing or finishing demising walls and
    public corridors with respect to such space and whether such work or alteration is performed for the initial occupancy by such tenant or thereafter and including any cash or other consideration paid on account of, with respect to or in lieu of any of
    the foregoing; (33) any incremental expenses incurred for use of any portion of the Land and/or the Building to accommodate special events not open to Tenant; (34)&#160;costs or payments associated with Landlord&#8217;s obtaining air rights or development rights;
    and (35) costs of design, entitlement, site preparation, planning, marketing, construction and/or acquisition of new buildings or of additional real property for or to the Land, or any expansion of the Building or Project.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Except as otherwise expressly set forth herein, those Operating Expenses that are incurred at a Project level shall be allocated based on the square footage and the
    type of use (<i>i.e.</i> retail, office, manufacturing, etc.). Project level Operating Expenses shall not include operating costs and expenses allocated to other buildings in the Project.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">5.1.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Audit Rights</u>. If Tenant objects to any
    Actual Statement and provides written notice to Landlord within ninety (90) days after its receipt of such Actual Statement, Tenant&#8217;s Auditor (as defined below) shall have the right, at Tenant&#8217;s sole cost and expense, upon at least thirty&#160;(30) days&#8217;
    prior notice to Landlord (which notice must be delivered within such ninety&#160;(90)-day period), at any time during regular business hours, to review and photocopy (or electronically copy) Landlord&#8217;s records pertaining to Operating Expenses for the
    immediately preceding year only, and only to the extent reasonably necessary to evaluate Tenant&#8217;s objections. The inspection of Landlord&#8217;s records must be completed within thirty&#160;(30) days after such records are made available to Tenant&#8217;s Auditor, and
    the written determination of Tenant&#8217;s Auditor must be delivered to Landlord within six&#160;(6) months after Tenant delivers written notice of its objection to the Actual Statement at issue. If Tenant fails to deliver the written determination of Tenant&#8217;s
    Auditor within said time period, Tenant shall forfeit any right to claim a refund, rebate, or return of Operating Expenses set forth in the applicable Actual Statement, except in the event of fraud or intentional misrepresentation. Tenant may engage a
    qualified employee in Tenant&#8217;s finance or accounting department or an independent contractor who (i) is hired by Tenant on a non-contingent fee basis, and (ii) specializes in real estate audits, to perform the audit (&#8220;<b>Tenant&#8217;s Auditor</b>&#8221;) to
    inspect Landlord&#8217;s records, subject to Landlord&#8217;s prior written approval, which approval shall not be unreasonably withheld or delayed. If, following the date Landlord receives the written report of Tenant&#8217;s Auditor (the &#8220;<b>Report Date</b>&#8221;), Landlord
    disputes the findings therein, and Landlord and Tenant are not able to resolve their differences within thirty&#160;(30) days following the Report Date, the dispute shall be resolved by binding arbitration as follows: Landlord and Tenant shall each
    designate an independent certified public accountant, who shall in turn jointly select an independent certified public accountant (the &#8220;<b>Independent CPA</b>&#8221;). Within sixty&#160;(60) days after selection, the Independent CPA shall review the relevant
    records and determine the proper amount of Operating Expenses payable by Tenant for the year in question, which determination shall be final and binding upon the parties. If the Independent CPA determines that the amount of Operating Expenses billed to
    Tenant was incorrect, the appropriate party shall pay to the other party the deficiency or overpayment, as applicable, within thirty&#160;(30) days following delivery of the Independent CPA&#8217;s decision, without interest. The fees and costs of the Independent
    CPA shall be paid by Tenant unless the Independent CPA determines that Tenant has overpaid Operating Expenses for the applicable year, in the aggregate, by more than three percent (3%), in which case Landlord shall pay the fees and costs of the
    Independent CPA, up to a maximum amount of Ten Thousand and No/100 Dollars ($10,000), and Tenant shall pay any remaining balance owing to the Independent CPA. Tenant shall keep all information obtained by Tenant in connection with its review of
    Landlord&#8217;s records confidential and obtain the agreement of Tenant&#8217;s Auditor and the Independent CPA to keep all such information confidential. Landlord may condition inspection of Landlord&#8217;s records by Tenant&#8217;s Auditor or the Independent CPA upon
    receipt of an executed confidentiality agreement acceptable to Landlord. Tenant agrees that Tenant&#8217;s sole right to inspect Landlord&#8217;s books and records and to contest the amount of Operating Expenses payable by Tenant shall be as set forth in this <u>Section&#160;5</u>.
    Notwithstanding the foregoing, if, as a result of Tenant&#8217;s timely audit of Operating Expenses and real estate Taxes for a given calendar year it is determined that the amounts paid by Tenant to Landlord on account of certain line items for Operating
    Expenses exceed the amounts to which Landlord was entitled by more than three percent (3%), then Tenant shall have the right to examine Landlord&#8217;s books and records for the two (2) previous calendar years as to such line items.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">5.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>General Payment Terms</u>. The Base Rent,
    Operating Expenses, late charges, default interest, and all other sums payable by Tenant to Landlord pursuant to this Lease are referred to collectively as the &#8220;<b>Rent</b>.&#8221; All Rent shall be paid in lawful money of the United States of America and
    through a domestic branch of a United States financial institution, by check or electronic payment. Checks are to be made payable to Landlord and mailed to 5465 Morehouse Drive, Suite 260, San Diego, California 92121, or to such other person or place
    as Landlord may, from time to time, designate to Tenant in writing. Wiring instructions for electronic payments, if available, will be provided separately. Rent for any fractional part of a calendar month at the commencement or termination of the Term
    shall be a prorated amount of the Rent for a full calendar month based upon a thirty&#160;(30) day month.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">5.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Interest</u>. Any installment of Rent and any
    other sum due from Tenant under this Lease which is not received by Landlord after expiration of all applicable notice and cure periods, shall bear interest from the date such payment was originally due under this Lease until paid at the Default Rate
    (as defined below); provided, however, with respect to the first late payment of Rent in any Lease year (and only such first late payment), interest shall not begin to accrue unless Tenant fails to pay such Rent within five (5) days after receipt of
    written notice from Landlord notifying Tenant of its failure to timely pay Rent. In addition, Tenant shall pay all costs and attorneys&#8217; fees incurred by Landlord in collection of such amounts.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">5.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Accord and Satisfaction</u>. No writing on any
    check, or statement in any letter or other document accompanying any payment of Rent from Tenant, and no acceptance by Landlord of less than the full amount of Rent owing, shall affect any accord and satisfaction. Any such partial payment shall be
    treated as a payment on account, and Landlord may accept such payment without prejudice to Landlord&#8217;s right to recover any balance due or to pursue any other remedy permitted by this Lease. Accordingly, Tenant hereby waives the provisions of California
    Uniform Commercial Code Section&#160;3311 (and any similar Laws that would permit an accord and satisfaction contrary to the provisions of this <u>Section&#160;5.4)</u>. Tenant waives any right to specify the items against which any Rent paid is to be credited,
    and Landlord may apply such payments to any Rent due or past due under this Lease. No payment, receipt or acceptance of Rent following (i)&#160;any Event of Default (as defined below); (ii)&#160;the commencement of any action against Tenant; (iii)&#160;termination of
    this Lease or the entry of judgment against Tenant for possession of the Premises; or (iv)&#160;the exercise of any other remedy by Landlord, shall cure the Event of Default unless otherwise agreed to in writing by Landlord, reinstate this Lease, grant any
    relief from forfeiture, continue or extend the Term, or otherwise affect or constitute a waiver of Landlord&#8217;s right to or the exercise of any remedy, including Landlord&#8217;s right to terminate this Lease and recover possession of the Premises. Tenant
    acknowledges and agrees that the foregoing constitutes actual notice to Tenant of the provisions of California Code of Civil Procedure&#160;&#167;1161.1(c). In order to give effect to the foregoing provisions, Landlord may (but is not required to) return to
    Tenant, at any time within fifteen&#160;(15) days after receiving same, any payment of any monetary amounts received from Tenant, including, but not limited to, Rent (x)&#160;that was paid following any Event of Default (irrespective of whether Landlord has
    commenced the exercise of any remedy), or (y)&#160;that is less than the amount due or owed. Each such returned payment (whether made by returning Tenant&#8217;s actual check, or by issuing a refund in the event Tenant&#8217;s check was deposited whether or not Tenant
    actually deposits or accepts such refund) shall establish that such payment was not received or approved by Landlord.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">5.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Late Charge</u>. Late payment of Rent or other
    amounts due hereunder will cause Landlord to incur costs not contemplated by this Lease, the exact amount of which will be extremely difficult to ascertain. If any Rent or other sums due from Tenant are not received by Landlord or by Landlord&#8217;s
    designated agent within five&#160;(5) days after their due date, then Tenant shall pay to Landlord a late charge equal to five percent (5%) of such overdue amount, plus any costs and attorneys&#8217; fees incurred by Landlord by reason of Tenant&#8217;s failure to pay
    Rent and/or other charges when due hereunder; provided, however, that Tenant shall be entitled to one notice of late payment and a five (5) day cure period in each twelve (12)-month period before any such late charge accrues. Landlord and Tenant hereby
    agree that such late charges represent a fair and reasonable estimate of the costs that Landlord will incur by reason of Tenant&#8217;s late payment and shall not be construed as a penalty. Landlord&#8217;s acceptance of such late charges shall not constitute a
    waiver of Tenant&#8217;s default with respect to such overdue amount or estop Landlord from exercising any of the other rights and remedies granted under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>6.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Use of Premises</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Permitted Use</u>. Subject to compliance with
    applicable Laws, including applicable zoning regulations, and this Lease, the Premises may be used solely for research and development, laboratory, biopharmaceutical manufacturing, assembly, storage, warehousing, office, administrative use related to
    products and merchandise made by Tenant (the &#8220;<b>Permitted Use</b>&#8221;); provided, however, Landlord shall not unreasonably withhold its approval of any Tenant request to change the Permitted Use. Tenant shall maintain and procure at Tenant&#8217;s own expense
    and responsibility all licenses, permits, or inspection certificates required by any governmental agency, court, regulatory or administrative agency, commission or authority or other legislative, executive or judicial governmental entity (in each case
    including any self-regulatory organization), whether federal, state or local, domestic, foreign or multinational (&#8220;<b>Governmental Authority</b>&#8221;) in respect to the Permitted Use and Tenant&#8217;s business in, on, or about the Premises, and Tenant shall
    promptly provide evidence thereof to Landlord upon Landlord&#8217;s request. Landlord makes no representation or warranty to Tenant that the Permitted Use is permitted by applicable Laws. During the Term, subject to the terms of this Lease and all applicable
    Laws, and subject to any emergencies, Tenant shall have the right to access the Premises twenty-four (24) hours per day, three hundred sixty-five (365) days per year.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Rules</u>. Landlord shall have the right to impose
    reasonable and customary rules and regulations (the &#8220;<b>Rules</b>&#8221;) regarding use of the Project, as reasonably deemed necessary by Landlord, and Tenant shall comply with such Rules to the extent such Rules are provided to Tenant in writing at least
    thirty (30) days prior to the effective date thereof. Landlord shall apply the Rules on a non-discriminatory basis to all similar tenants in the Project.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Governing Documents</u>. As of the Effective Date,
    Landlord has complied with and, to its knowledge, is not in default of and shall at all times during the Term of this Lease continue to comply with its obligations as to the Premises under the Commercial DDA, all Governing Documents and any Rules and
    regulations adopted pursuant thereto. Until Substantial Completion of Landlord&#8217;s Work, Landlord agrees to provide Tenant with any written notice of default or breach under the Commercial DDA as to the Premises or any Governing Documents. The existing
    Governing Documents are set forth on <u>Exhibit E</u>, attached hereto and incorporated herein. Without the prior written consent of Tenant, which will not be unreasonably withheld, conditioned, or delayed, Landlord will not take any of the following
    actions: (i) consent to any amendment of the Governing Documents or Commercial DDA that will have an adverse impact on the Premises or Tenant&#8217;s access to or use thereof (each, an &#8220;<b>Amendment</b>&#8221;), (ii)&#160;other than in connection with the financing or
    refinancing of the Premises or Project which complies with <u>Section 18</u> below, permit any encumbrance on title with respect to the Premises if they will adversely affect Tenant&#8217;s rights or obligations under this Lease (each a &#8220;<b>New Project
      Document</b>&#8221;), or (iii) to the extent in Landlord&#8217;s control, cause or permit any governing associations to adopt any assessments if they will adversely affect Tenant&#8217;s rights or obligations under this Lease (each, an &#8220;<b>Association Act</b>&#8221;). In
    the event Tenant&#8217;s consent is required, Tenant shall respond to Landlord&#8217;s request for consent within ten (10) days and any refusal to provide consent must be made with specificity sufficient to assist Landlord in revising. Tenant shall respond in
    writing (with detailed reasons for any disapproval) to any revised request within ten (10) days following receipt of such request, and any failure to provide a written response within such ten-day period shall be deemed an approval.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Prohibited Uses</u>. Tenant shall not use, or
    suffer or permit any use of the Premises, the Project, or any part thereof in violation of any Laws, this Lease, the Governing Documents, or the Rules. Tenant shall not do or permit anything to be done in or about the Premises or the Project which will
    damage the reputation of the Project or unreasonably and materially obstruct or interfere with the rights of other tenants or occupants of the Project, nor shall Tenant cause, maintain, or permit any nuisance in or about the Premises or the Project.
    Tenant shall not do, bring, or keep anything in or about the Premises that will cause a cancellation of any insurance covering the Premises. No machinery, equipment, apparatus, or other appliance shall be used or operated in or on the Premises that
    will unreasonably interfere with the equipment of any other tenant within the Project, including, without limitation, interference with transmission and reception of telephone, telecommunications, television, radio, or similar signals. Tenant shall not
    use the Premises in any manner that will cause the Building or any part thereof not to conform with the Building&#8217;s Sustainability Practices or the certification of the Building issued pursuant to the applicable Green Building Standards, if any;
    provided, however, that in no event shall such practices or certification requirements have the effect of preventing Tenant from conducting its business at the Premises in a manner consistent with the Permitted Use.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Access</u>. Landlord acknowledges and agrees that,
    except as otherwise expressly set forth in this Lease, Tenant shall have full responsibility for the maintenance and repair of and shall have unfettered access and control over the Premises throughout the Term of the Lease. Subject to Tenant&#8217;s security
    requirements as set forth on <u>Exhibit F</u> attached hereto, as may be amended, and to the provisions of this <u>Section 6.5</u>, (i) Landlord, its agents, contractors and representatives may enter the Premises to inspect or show the Premises to
    prospective or existing lenders or purchasers, or to prospective tenants (with prospective tenants being shown the Premises only within the last twelve (12) months of the Term), to confirm Tenant is complying with its obligations under this Lease, to
    comply with Landlord&#8217;s obligations under this Lease, to clean and make repairs, alterations or additions to the Premises to the extent permitted by this Lease, and (ii)&#160;in case of emergencies or to comply with applicable Laws or orders of Governmental
    Authority, Landlord shall have the right to temporarily close all or a portion of the Premises to perform inspections, repairs, alterations and additions. Except in the case of emergencies or to comply with applicable Laws or orders of Governmental
    Authority, Landlord shall provide Tenant with at least one (1) business day prior notice of entry into the Premises, which may be given via e-mail. Landlord shall also comply with any governmental regulations as are applicable to the Permitted Use or
    any reasonable security protocols of Tenant regarding access to secured or controlled rooms or areas within the Premises. Landlord will not close the Premises if the work can reasonably be completed on weekends and after normal business hours. Entry by
    Landlord shall not constitute constructive eviction or entitle Tenant to an abatement or reduction of Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Environmental Requirements</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Definitions</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Contamination</b>&#8221; or &#8220;<b>Contaminated</b>&#8221; means any
    Hazardous Materials or toxic material, substance, chemical or waste, contaminant, emission, discharge or pollutant or comparable material listed, identified, or regulated pursuant to any Environmental Requirement (as defined below) or federal, state or
    local law, ordinance or regulation which has as a purpose the protection of health, safety or the Environment (as defined below), resulting from any cause, Release (as defined below), or source.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Environment</b>&#8221; means all forms of fauna, flora,
    soil, natural resources; surface, subsurface, or ground waters; land, ground, surface, or subsurface strata; ambient air; or any other environmental medium, including the indoor environment, contained within, or affected by the Premises or operations
    thereon.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Environmental Claim(s)</b>&#8221; means any claim, action,
    suit, proceeding, enforcement action, administrative proceeding, liability, loss, demand, damage (including punitive damages and damages based upon diminution in value or loss of use of the Premises or Project), encumbrance, cause of action of any
    kind, order, subpoena, obligation, cost, expense, royalty, fee, assessment, duty, requirement, charge, penalty, fine, forfeiture, judgment, injunctive relief, interest, and award (including recoverable legal counsel fees and cost of litigation of the
    party asserting the claim), whether arising by law, contract, tort, voluntary settlement, or in any other manner resulting from or in any way associated with:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(A) acts or omissions of Tenant or any Tenant Party (as defined below) with respect to, or occurring on, the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(B) Tenant&#8217;s control, use, possession, or operation of the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(D) any condition existing or occurring in, on, under or within the Premises after the Lease Commencement Date;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(E) the damage or destruction of the Premises, the Project or any adjacent property resulting from the storage, use, handling, generation, or
    Release of Hazardous Materials from the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(F) the violation or alleged violation of any Environmental Requirement;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(F) the existence, assessment, or remediation of Contamination upon, under, in or emanating from, the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(G) emissions, discharges, Releases or threatened Releases, or the presence, generation, manufacturing, processing, distribution, use, treatment,
    storage, disposal, transport, labeling, advertising, sale, display, or handling, of Contamination;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(H) any special, indirect, or consequential damages, including, but not limited to, claims for loss of use, rents, anticipated profit or business
    opportunity, or business interruption, diminution in value, or mental or emotional distress or fear of injury or illness, trespass, nuisance or otherwise related in any way to the Premises; or</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">(I) any response costs any member of the Tenant or Landlord may incur with respect to the Premises under any Environmental Requirement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Environmental Condition</b>&#8221; means Contamination at,
    on, under or emanating to or from the Premises or a condition or circumstance relating to the Premises or operation thereof which is or is alleged to be not in compliance with Environmental Requirements.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Environmental Requirement(s)</b>&#8221; means any present
    and future Laws, regulations, statutes, codes, rules, orders, permits, policies, licenses, certifications, decrees, standards, or interpretations imposed by any Governmental Authority relating to pollution; the protection of the Environment; the
    Release, emission, discharge or disposal of any material or chemical substance; human health or safety; Hazardous Materials; natural resource damage; product registration; hazard communication, each as from time to time has been or may be amended or
    adopted before or after the Effective Date, including any of the following: The Occupational Safety and Health Act, 29 U.S.C.A. &#167; 651, <i>et seq.</i>; the Resource Conservation and Recovery Act, 42 U.S.C.A. &#167; 6901, <i>et seq.</i>; the Comprehensive
    Environmental Response, Compensation, and Liability Act, 42 U.S.C.A. &#167; 9601, <i>et seq.</i>; the Clean Water Act, 33&#160;U.S.C.A. &#167;1251, <i>et seq.</i>; the Clean Air Act, 42 U.S.C.A. &#167; 7401, <i>et seq.</i>; the Safe Drinking Water Act, 42 U.S.C.A. &#167;
    3001, <i>et seq.</i>; the Toxic Substances Control Act, 15 U.S.C.A. &#167; 2601, <i>et seq.</i>; the Oil Pollution Act of 1990, 33 U.S.C.A. &#167; 2701, <i>et seq.</i>; the California Underground Storage of Hazardous Substances Act, H&amp;S C &#167;&#167; 25280, <i>et
      seq.</i>; the California Hazardous Substances Account Act, H &amp; S C &#167;&#167; 25300, <i>et seq.</i>; the California Hazardous Waste Control Act, H&#160;&amp;&#160;S&#160;C&#160;&#167;&#167;&#160;25100, <i>et seq.</i>; the California Safe Drinking Water and Toxic Enforcement Act,
    H&#160;&amp;&#160;S&#160;C&#160;&#167;&#167;&#160;24249.5, <i>et seq.</i>; and the Porter-Cologne Water Quality Act, Wat C &#167;&#167; 13000, <i>et seq.</i> As defined in Environmental Requirements, Tenant is and shall be deemed to be the &#8220;operator&#8221; of Tenant&#8217;s &#8220;facility&#8221; and the &#8220;owner&#8221; of
    all Hazardous Materials brought on the Premises by Tenant or any Tenant Party, and the wastes, by-products, or residues generated, resulting, or produced therefrom.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Hazardous Materials</b>&#8221; means a substance, chemical,
    product, waste or other material that, because of its physical, chemical, or other characteristics, may pose a risk of endangering human health or safety or of degrading the Environment, or which is, or becomes identified, listed, published, regulated,
    or defined as, or which shows the characteristics of, a hazardous substance, hazardous waste, hazardous material, toxic substance or other regulatory term, including oil, oil waste, by-products and components, NORM, Hydrocarbons, and Hydrocarbons
    waste, produced water, by-products and components, polychlorinated biphenyls, and asbestos, or which is otherwise regulated or restricted under any Environmental Requirements or by any Governmental Authority, or which may otherwise cause, contribute to
    or result in an Environmental Condition or Environmental Condition. &#8220;Hazardous Materials&#8221; include, but are not limited to, all of the following: (1) a hazardous substance, as defined in Section 25281 or 25316 of the California Health and Safety Code;
    (2) a hazardous waste, as defined in Section 25117 of the California Health and Safety Code; (3) a waste, as defined in Section 470 of the California Health and Safety Code or as defined in Section 13050 of the California Water Code; and/or (4) any
    substance or material that is defined or designated as a hazardous waste, material or substance by any other applicable Environmental Requirements, including, without limitation, perfluoroalkyl substances (PFAS).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Release</b>&#8221; or &#8220;<b>Released</b>&#8221; or &#8220;<b>Releases</b>&#8221;
    means any release, deposit, discharge, emission, leaking, spilling, seeping, migrating, injecting, pumping, pouring, emptying, escaping, dumping, disposing, or other movement of Hazardous Materials into the Environment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">6.6.1.8<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>&#8220;<b>Remediation</b>&#8221; or &#8220;<b>Remediate</b>&#8221; means any and
    all actions required to be taken under the Environmental Requirements or otherwise to address an Environmental Condition, including investigation, monitoring, removal, remediation, corrective action, response action, mitigation, treatment,
    decontamination, or cleanup of (1) Hazardous Materials, (2) pollution or (3) Contamination, present or alleged to be present on, under or emanating from the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Prohibition/Indemnity</u>. Tenant shall not
    cause or permit any Hazardous Materials to be brought upon, kept, used, stored, handled, treated, generated in or about, Released or disposed of from the Premises in violation of applicable Environmental Requirements. If Tenant breaches any obligations
    set forth in this <u>Section&#160;6.6</u>, or if the presence of Hazardous Materials in, on, about, or under the Premises during the Term or any holding over or any other occupancy results in contamination of the Premises, the Project, or any adjacent
    property or if Contamination of the Premises, the Project, or any adjacent property by Hazardous Materials brought into, kept, used, stored, handled, treated, generated in or about, or Released or disposed of from the Premises by anyone other than
    Landlord and the Landlord Parties otherwise occurs during the Term or any holding over, Tenant hereby indemnifies and shall defend and hold Landlord and the Landlord Parties harmless from any and all Environmental Claims which arise during or after the
    Term as a result thereof. This indemnification by Tenant includes, without limitation, costs incurred in connection with any Remediation required by any federal, state or local Governmental Authority because of Hazardous Materials present in the air,
    soil or ground water above, on, or under the Premises.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Contamination</u>. Without limiting Tenant&#8217;s
    indemnity obligation in <u>Section&#160;6.6.2</u> above, if the presence of any Hazardous Materials in, on, under, or about the Premises, the Building, the Project, or any adjacent property caused or permitted by Tenant, its agents, employees or
    contractors, results in any Contamination of the Premises, the Building, the Project or any adjacent property, Tenant shall promptly take all actions at its sole expense and in accordance with applicable Environmental Requirements as are reasonably
    necessary and appropriate, in Landlord&#8217;s reasonable discretion, to return the Premises, the Building, the Project, or any adjacent property substantially to the condition existing prior to the time of such Contamination; provided, however, Tenant shall
    first prepare and submit to Landlord, within thirty (30) days of learning of such Contamination or within such earlier time as required to comply with Environmental Requirements or Governmental Authority, a comprehensive plan specifying the actions to
    be taken by Tenant to Remediate the Contamination and restore the Premises to the conditions required by this Lease. Such plan shall include Tenant&#8217;s timeframes to cause all such Remediation actions to be taken and any consultant(s) engaged for the
    performance of the Remediation. Landlord&#8217;s approval of Tenant&#8217;s Remediation plan shall first be obtained before Tenant takes any action, which approval shall not unreasonably be withheld so long as such actions would not potentially have any material
    adverse long-term or short-term effect on the Premises, the Building or the Project. Upon Landlord&#8217;s approval of Tenant&#8217;s Remediation plan (as so approved, the &#8220;<b>Clean-Up Plan</b>&#8221;), Tenant shall, at Tenant&#8217;s sole cost and expense, without limitation
    on any rights and remedies of Landlord under this Lease, immediately implement the Clean-Up Plan with a consultant reasonably acceptable to Landlord and proceed to act in accordance with all applicable Environmental Requirements and this Lease. If
    Tenant fails to implement the actions in the Clean-Up Plan as set forth therein, Landlord shall have the right, but not the obligation, and without waiving any other rights and remedies under this Lease, following written notice to Tenant, to carry out
    such actions and recover the costs and expenses thereof from Tenant as Rent, payable within thirty (30) days after receipt of written demand therefor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Business</u>. Landlord acknowledges that it is
    not the intent of this <u>Section&#160;6.6</u> to prohibit Tenant from using the Premises for the Permitted Use. Tenant may operate its business according to prudent industry practices so long as the use or presence of Hazardous Materials is strictly and
    properly monitored according to all then-applicable Environmental Requirements. As a material inducement to Landlord to allow Tenant to use Hazardous Materials in connection with its business, Tenant represents and warrants that it has fully and
    accurately completed the Environmental Questionnaire which is attached to this Lease as <u>Exhibit C</u> (the &#8220;<b>Environmental Questionnaire</b>&#8221;). Tenant agrees to provide Landlord with annual updates of any changes in its use of Hazardous Materials
    not listed and described in the Environmental Questionnaire most-recently submitted to Landlord. Landlord shall not have any approval rights over such updates, provided the Hazardous Materials proposed to be used by Tenant are of a type and in such
    quantities as are reasonable and customary for the Permitted Use. Tenant agrees that, except as set forth on the Environmental Questionnaire (as it may be updated pursuant to this Section), neither Tenant nor any Tenant Party will produce, use, store,
    or generate any Hazardous Materials on, under, or about the Premises nor cause or permit any Hazardous Materials to be brought upon, placed, stored, manufactured, generated, blended, handled, recycled, used or released, on, in, under, or about the
    Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Haz Mat Documents</u>. Upon Landlord&#8217;s request,
    or any time that Tenant is required to deliver a Hazardous Materials list to any Governmental Authority in connection with Tenant&#8217;s use or occupancy of the Premises, Tenant shall deliver to Landlord a copy of such Hazardous Materials list. Tenant
    shall, prior to the Rent Commencement Date, deliver to Landlord true and correct copies of the following documents (the &#8220;<b>Haz Mat Documents</b>&#8221;) relating to the use, storage, handling, treatment, generation, Release or disposal of Hazardous
    Materials at the Premises, or if unavailable at that time, concurrent with the receipt from or submission to a Governmental Authority, without regard to whether such materials are generated by Tenant or prepared for Tenant, or how Tenant comes into
    possession of such materials; permits; licenses; certifications; approvals; reports, audits, assessments, studies, and correspondence; storage and management plans; notice of violations of any Environmental Requirements; plans relating to the
    installation of any storage tanks to be installed in or under the Land (provided, said installation of tanks shall only be permitted after Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s sole and
    absolute discretion); and all Remediation plans, closure plans or any other documents required by any and all federal, state and local Governmental Authority for any storage tanks installed in, on or under the Land for the closure of any such tanks.
    Tenant is not required, however, to provide Landlord with any portion(s) of the Haz Mat Documents containing information of a proprietary nature which, in and of themselves, do not contain a reference to any Hazardous Materials or hazardous activities.
    It is not the intent of this Section to provide Landlord with information which could be detrimental to Tenant&#8217;s business should such information become possessed by Tenant&#8217;s competitors. Tenant shall keep confidential and not disclose, discuss,
    disseminate, or copy any information, data, findings, communications, conclusions and reports regarding the Environmental Condition of the Premises to any person or entity, including any Governmental Authority (other than Tenant&#8217;s consultants,
    attorneys, property managers, and employees that have a need to know such information), without the prior written consent of Landlord, unless Tenant is compelled to do so by applicable Environmental Requirements. If Tenant reasonably believes that
    disclosure is required by applicable Environmental Requirements, Tenant shall provide Landlord with at least ten (10) days&#8217; advance written notice to allow Landlord to attempt to obtain a protective order.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Environmental Report</u>. Tenant
    acknowledges that, prior to the Effective Date, Landlord delivered to Tenant a copy of Landlord&#8217;s final Phase I environmental site assessment regarding the Land for Tenant&#8217;s review prior to its execution of this Lease. Except as disclosed therein,
    Landlord represents and warrants that, to its knowledge, there are no Hazardous Materials on or under the Building, the Land, the Common Areas, or the Premises. Landlord covenants not to bring onto the Premises any Hazardous Materials in violation of
    applicable Environmental Requirements. Landlord shall indemnify Tenant and hold it harmless against any third-party claims, damages, losses or liabilities (including without limitation reasonable attorney&#8217;s fees) incurred by Tenant arising from any
    uncured breach of the foregoing representation and warranty. In no event shall Tenant be responsible for the costs (and such costs shall not be included in Operating Expenses) of removal or any Remediation required due to the presence of Hazardous
    Materials outside the Premises not caused by Tenant or any Tenant Party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Notices</u>. Tenant shall notify Landlord in
    writing as soon as possible but in no event later than three (3) days after Tenant becomes aware of any of the following (collectively, &#8220;<b>Hazardous Materials Claims</b>&#8221;): (i) the occurrence of any actual, alleged, or threatened Release of any
    Hazardous Materials in, on, under, from, about, or in the vicinity of the Premises, regardless of the source or quantity of the Release, (ii) any regulatory actions, inquiries, inspections, investigations, directives, or any cleanup, compliance,
    enforcement, or abatement proceedings (including any threatened or contemplated actions) relating to or potentially affecting the Premises with respect to any actual, alleged, or threatened Release, or (iii)&#160;any claims by any person or entity relating
    to any Hazardous Materials in, on, under, from, about, or in the vicinity of the Premises. Tenant shall promptly forward to Landlord copies of any non-privileged documentation or correspondence received, prepared, or distributed regarding any Hazardous
    Materials Claims.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.8<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Testing</u>. Landlord shall have the right to
    conduct annual tests of the Premises to determine any violation of Tenant&#8217;s obligations under this <u>Section&#160;6.6</u>, and to conduct additional tests at any time upon reasonable suspicion of a Release. Tenant shall pay the cost of such tests of the
    Premises; provided, however, that if Tenant conducts its own tests of the Premises using third party contractors and test procedures with Landlord&#8217;s prior, written consent, which test data and reports are immediately provided to Landlord, Landlord
    shall accept such tests in lieu of the annual tests to be obtained by Landlord and paid by Tenant. Landlord&#8217;s receipt of or satisfaction with any test results in no way waives any rights or remedies which Landlord may have against Tenant or any other
    person or entity. Tenant shall, at its sole cost and expense, promptly and satisfactorily remediate any environmental conditions identified by such testing in accordance with all Environmental Requirements, including without limitation, by complying
    with all of Tenant&#8217;s obligations set forth in this <u>Section&#160;6.6</u> which are applicable thereto.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.9<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Pre-Existing and Migrating Conditions</u>.
    Notwithstanding anything to the contrary contained in this&#160;<u>Section&#160;6.6</u>, Tenant shall not be responsible for the indemnification and hold harmless obligation set forth in&#160;<u>Section&#160;6.6.2</u>, which shall not apply to (i)&#160;contamination in, on or
    under the Premises which Tenant can prove existed in, on, or under the Premises immediately prior to the Lease Commencement Date, or (ii) the presence of any Hazardous Materials in, on or under the Premises which Tenant can prove migrated from outside
    of the Premises into the Premises, unless in either case, the presence of such Hazardous Materials (x) is the result of a breach by Tenant of any of its obligations under this Lease, or (y) to the extent it was caused, contributed to, or exacerbated by
    Tenant, its agents, employees, or contractors.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.10<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font><u>Underground Tanks</u>. In no event shall Tenant
    have the right to install underground tanks.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.6.11<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font><u>Tenant&#8217;s Obligations</u>. Tenant&#8217;s obligations
    under this&#160;<u>Section&#160;6.6</u> shall survive the expiration or earlier termination of this Lease. During any period of time, whether during or after the expiration or earlier termination of this Lease, required by Tenant or Landlord to complete the
    Remediation of the Premises of any Hazardous Materials (including, without limitation, the Release and termination of any licenses or permits restricting the use of the Premises and the completion of any Clean-Up Plan or the approved Surrender Plan (as
    defined below)), Tenant shall continue to pay the full Rent in accordance with this Lease for any portion of the Premises not relet by Landlord in Landlord&#8217;s sole but reasonable discretion, which Rent shall be prorated daily.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Accessibility</u>. Tenant acknowledges that the
    Premises, the Building and the Project are subject to, among other Laws, the requirements of the Americans with Disabilities Act, a federal law codified at 42 U.S.C. &#167; 12101, <i>et seq.</i>, including, but not limited to Title&#160;III thereof (&#8220;<b>Disabilities







      Act</b>&#8221;), and all regulations and guidelines related thereto, together with any and all similar Laws, rules, regulations, ordinances, codes and statutes now or hereafter enacted by local or state agencies having jurisdiction thereof, as the same may
    be in effect on the date of this Lease and may be hereafter modified, amended or supplemented (collectively, the &#8220;<font style="font-family: Times New Roman, Times, Serif"><b>Accessibility Laws</b></font>&#8221;). As of the Lease Commencement Date, Landlord
    represents that the Building and all of Landlord&#8217;s Work shall comply in all material respects with Accessibility Laws. Provided the Building and Landlord&#8217;s Work is in compliance as of the Lease Commencement Date with applicable Laws, including without
    limitation Accessibility Laws, Tenant shall be solely responsible for investigating and confirming that all TI Work (as defined in <u>Section 3</u> of the Work Letter) and Alterations comply with Accessibility Laws. Furthermore, from and after the
    Lease Commencement Date, subject to the provisions hereof, Tenant shall be responsible at its sole cost and expense for fully and faithfully complying with all applicable requirements of Accessibility Laws pertaining to the Premises. Within ten&#160;(10)
    days after receipt, Landlord and Tenant shall advise the other in writing, and provide such party with copies of (as applicable), any notices alleging violation of Accessibility Laws relating to any portion of the Premises, the Building or the Project;
    any claims made or threatened orally or in writing regarding noncompliance with Accessibility Laws and relating to any portion of the Premises, the Building or the Project; or any governmental or regulatory actions or investigations instituted or
    threatened regarding noncompliance with Accessibility Laws and relating to any portion of the Premises, the Building or the Project. Landlord and Tenant shall and hereby agree to protect, defend (with counsel acceptable to the other party) and hold
    Landlord and Tenant (as applicable) and their respective agents (as applicable) harmless and indemnify such parties from and against all liabilities, damages, claims, losses, penalties, judgments, charges and expenses (including attorneys&#8217; fees, costs
    of court and expenses necessary in the prosecution or defense of any litigation including the enforcement of this provision) arising from or in any way related to, directly or indirectly, the other party&#8217;s violation or alleged violation of
    Accessibility Laws. The obligations of Landlord and Tenant herein shall survive the expiration or earlier termination of this Lease.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>7.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Alterations</u></b>.
    Any alterations, additions, or improvements to the Premises by Tenant after completion of the TI Work (collectively referred to as &#8220;<b>Alterations</b>&#8221;) shall be subject to the terms and conditions of this&#160;<u>Section 7</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Cosmetic Alterations</u>. Landlord&#8217;s consent shall
    not be required for any Alteration that satisfies all of the following criteria (a &#8220;<b>Cosmetic Alteration(s)</b>&#8221;): (a)&#160;does not require a permit or other government approval to undertake; (b)&#160;is not visible from the exterior of the Building; (c)&#160;will
    not materially and adversely affect the Building (as opposed to Premises) plumbing, sewer, drainage, electrical, fire protection, life safety and security systems and equipment, heating, ventilation, and air conditioning systems (collectively, the &#8220;<b>Building







      Systems</b>&#8221;), or the exterior walls, foundation, roof (including roof membrane), or structural portions of the floor (the &#8220;<b>Building Structure</b>&#8221;); (d)&#160;the aggregate cost of all such Cosmetic Alterations in any consecutive twelve (12)-month
    period does not exceed One Million and No/100 Dollars ($1,000,000.00); and (e)&#160;do not require the consent or approval of, or other review or documentation by, any Mortgagee (as defined below) pursuant to loan documents then in effect provided Landlord
    delivered to Tenant prior written notice of any such requirements. Even though consent is not required, Tenant must provide written notice of any proposed Cosmetic Alteration to Landlord (with reasonable detail) at least thirty (30) days prior to
    beginning any Cosmetic Alteration with the exception of minor alterations including painting, wallpapering and hanging pictures, for which no notice shall be required. The performance of Cosmetic Alterations shall also be subject to all the other
    provisions of this&#160;<u>Section 7.1</u>. Notwithstanding anything herein to the contrary, in no event shall consent be required prior to the installation of movable furniture or equipment not affixed to or incorporated into the Premises in any manner and
    which, in any event, satisfies the criteria of a Cosmetic Alteration; provided, however, the $1,000,000 limit in <u>Section&#160;7.1(d)</u> shall not apply.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requirements for Alterations</u>. Any Alterations
    other than Cosmetic Alterations will require Landlord&#8217;s prior written approval, which shall not be unreasonably withheld, conditioned, or delayed. At least fifteen (15) business days prior to starting work on any Alterations, Tenant shall furnish
    Landlord with plans and specifications reasonably acceptable to Landlord (except that Landlord&#8217;s approval with respect to the specifications for Cosmetic Alterations shall not be required); names of contractors, which such contractors shall be subject
    to Landlord&#8217;s reasonable approval as to any non-Cosmetic Alteration; copies of necessary permits and approvals; and evidence of contractor&#8217;s insurance in amounts reasonably required by Landlord. Material changes to the plans and specifications
    (excluding changes that would be considered Cosmetic Alterations) must be submitted to Landlord for its reasonable approval. Tenant acknowledges and agrees that Tenant, at Tenant&#8217;s expense, is responsible for performing all accessibility and other work
    required to be performed in connection with the Alterations, including, but not limited to, any &#8220;path of travel&#8221; or other work outside the Premises to the extent necessitated as a result of Tenant&#8217;s proposed Alterations; provided, however, that
    Landlord may elect upon written notice to Tenant, to perform any such work in the Common Areas or elsewhere outside of the Premises, at Tenant&#8217;s expense. If Landlord elects to perform such work outside the Premises, then prior to the commencement of
    such Alterations by Tenant, Tenant shall deposit with Landlord, Landlord&#8217;s reasonable estimate of the cost of performing such work, including the reasonable and actual cost of Landlord&#8217;s construction manager. Alterations shall be performed in a good
    and workmanlike manner, in compliance with all applicable Laws, the Building&#8217;s Sustainability Practices and Green Building Standards, if any, and Landlord requirements, including the Work Letter and the requirements of any insurer providing coverage
    for the Premises, the Building or the Project. Alterations shall be performed free of mechanic&#8217;s and materialmen&#8217;s liens and of any claims therefor. If Tenant fails to remove any such lien by bond or otherwise within ten (10) business days after notice
    from Landlord, Landlord may pay the amount necessary to remove such lien, without being responsible for investigating the validity thereof, and Tenant shall reimburse Landlord therefor within ten (10) business days after receipt of an invoice therefor.
    All Alterations, including Cosmetic Alterations, shall be at Tenant&#8217;s sole cost and expense. Tenant shall reimburse Landlord, as Rent, within thirty (30) days of demand (which such demand shall include reasonable backup documentation), for any actual,
    reasonable out-of-pocket costs incurred by Landlord in connection with reviewing the plans and specifications with respect to any Tenant Alterations. Furthermore, Landlord shall have the right (but not an obligation) to monitor construction of the
    Alterations, and to require corrections of faulty construction or any material deviation from the plans for such Alterations as approved, and Tenant shall reimburse Landlord for its reasonable and actual third party costs (including, but not limited
    to, the reasonable and actual costs of any construction manager retained by Landlord) in monitoring construction; provided, however, that no such inspection shall be deemed to create any liability on the part of Landlord, or constitute a representation
    by Landlord or any person hired to perform such inspection that the work so inspected conforms with such plans or complies with any applicable Laws, and no such inspection shall give rise to a waiver of, or estoppel with respect to, Landlord&#8217;s
    continuing right at any time or from time to time to require the correction of any faulty work or any material deviation from such plans. In no event shall Landlord be entitled to reimbursement for any costs to monitor construction of the Alterations
    (including the costs of any construction or project manager) in excess of 1% of the hard costs of construction of the Alteration.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Removal of Alterations</u>. Tenant&#8217;s obligation to
    remove any Alterations upon the expiration or earlier termination of this Lease shall be as set forth in <u>Section 19</u>, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>8.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Maintenance and
        Repairs; Utilities</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Maintenance by Landlord</u>. This Lease is
    intended to be a net lease. Subject to <u>Section&#160;6 </u>above and Sections <u>10</u> and <u>11</u> below, Landlord shall, at Landlord&#8217;s sole cost, repair any latent defects in Landlord&#8217;s Work; the foregoing obligation shall not at any time ever
    include any TI Work, Tenant&#8217;s Work (as defined in Section 3 of the Work Letter), or Alterations, except in the event any defects in the original construction of the Building or Landlord&#8217;s Work caused the necessity for repairs. In addition,&#160;Landlord
    shall maintain, repair and replace (as needed), as part of Operating Expenses, only the following elements of the Project including the Premises, except to the extent maintained by an owners&#8217; association: (i) the Building Structure; (ii) the Building
    Systems which do not exclusively serve the Premises or another tenant&#8217;s premises; and (iii) the Common Areas outside the Premises, including landscaping and parking areas but not including the maintenance and repair of electrical vehicle charging
    stations which shall be Tenant&#8217;s responsibility pursuant to&#160;<u>Section 8.2</u>&#160;below. Notwithstanding the foregoing, subject to&#160;<u>Section&#160;9.5</u> below, maintenance, repairs and/or replacements necessitated in any material respect by any breach by
    Tenant or any negligent act or omission of Tenant or Tenant&#8217;s agents, employees or contractors, shall be performed at Tenant&#8217;s cost and expense. Landlord&#8217;s obligations hereunder shall not include windows, glass or plate glass, doors or overhead doors,
    dock bumpers, dock plates or levelers, or office entries, all of which shall be maintained by Tenant. Tenant shall promptly give Landlord written notice of any repair required by Landlord pursuant to this&#160;<u>Section 8.1</u>, after which Landlord shall
    have a reasonable opportunity to repair such item, not to exceed thirty (30) days; provided, however, if such repair is reasonably expected to take longer than thirty (30) days, Landlord shall be deemed to have complied with its obligations hereunder
    so long as it commences the repair within such thirty (30)-day period and diligently and continuously prosecutes such repair to completion. Tenant hereby waives the benefit of California Civil Code Sections 1941 and 1942, and any other statute
    providing a right to make repairs and deduct the cost thereof from the Rent.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Maintenance by Tenant</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Subject to Landlord&#8217;s obligations in&#160;<u>Section&#160;
      8.1</u> above, Tenant, at its sole expense, shall repair, replace and maintain in good condition and in compliance with all applicable Laws all portions of the Premises and the Building and all areas, improvements and systems serving the Premises
    including, without limitation, all aspects of Tenant&#8217;s Work and any Alterations, dock, dock equipment and loading areas, the equipment yard, truck doors, plumbing, water, and sewer lines up to points of common connection, entries, doors, door frames,
    ceilings, windows, window frames, interior walls, and the interior side of demising walls, heating, ventilation and air conditioning systems and other building and mechanical systems exclusively serving the Premises, the fire sprinklers and fire
    protection systems serving the Building&#160;(including the monitoring thereof), and repairing and maintaining the electrical charging stations within the parking areas of the Premises. Such repair and replacements shall include capital expenditures and
    repairs whose benefit may extend beyond the Term. Tenant shall have access to enter upon such parts of the Project reserved to Landlord, and to Common Areas as necessary to comply with its obligations under this <u>Section 8.2</u>. Tenant, at Tenant&#8217;s
    expense, shall enter into commercially reasonable and customary maintenance service contracts for the maintenance and repair of the heating, ventilation and air conditioning systems and other mechanical and Building Systems exclusively serving the
    Premises. Upon request, Landlord shall, at no material cost or expense to Landlord, reasonably cooperate with Tenant as necessary for Tenant to fully perform the requirements of this Section.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.2.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>In the event that any repair or maintenance
    obligation required to be performed by Tenant hereunder may affect any portion of the Building Structure or which would likely materially, adversely affect any Building Systems, prior to commencing any such repair, Tenant shall provide Landlord with
    written notice of the necessary repair or maintenance and a brief summary of the component or components of the Building Structure, and/or the Building Systems, that may be affected by such repair or maintenance. Within&#160;five (5) days after Landlord&#8217;s
    receipt of Tenant&#8217;s written notice, Landlord shall have the right, but not the obligation, to elect to cause such repair or maintenance to be performed by Landlord, or a contractor selected and engaged by Landlord, but at Tenant&#8217;s sole cost and expense
    provided the cost therefor shall not materially exceed the cost that Tenant would have paid for the same service, and further provided the repairs or maintenance are performed within the same timeframe that Tenant would have caused the repairs or
    maintenance to be performed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.2.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Unless Landlord elects to cause the repair or
    maintenance to be performed by Landlord or a contractor selected and engaged by Landlord as set forth in <u>Section&#160;8.2.2</u> above, if Tenant fails to perform any repair or replacement for which it is responsible within the time periods set forth
    herein and Tenant fails to commence such repair or replacement within ten (10) business days (unless such repair will, due to the nature of the repair, reasonably require a period of time in excess of&#160;ten (10) business days to commence such cure, then
    such additional period of time as is reasonably necessary) after receipt of Landlord&#8217;s written notice (or sooner in the event of an emergency condition that poses an imminent threat to life or material damage to property), then Landlord may perform
    such work and be reimbursed by Tenant for its actual out-of-pocket costs in connection therewith within&#160;thirty (30) days after its receipt of written demand therefor (which demand shall be accompanied by reasonable supporting documentation). Subject to
    <u>Sections 9</u> and <u>10</u> below, Tenant shall bear the full cost of any repair or replacement to any part of the Building or Project that results from damage caused by Tenant or its agents, employees or contractors, and any repair that benefits
    only the Premises.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.2.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>As long as Tenant is performing its repair and
    maintenance obligations under this <u>Section&#160;8.2</u>&#184; and notwithstanding anything to the contrary in <u>Section&#160;5.1</u> above, Landlord shall not charge Tenant, and Tenant shall not be obligated to pay, as part of Tenant&#8217;s Proportionate Share of
    Operating Expenses, a management fee in excess of three-quarters of one percent (0.75 %) of the net rent of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Utilities</u>. Tenant shall contract with and
    directly pay when due utility company charges for all water, gas, electricity, heat, light, power, telephone, sewer, sprinkler services, refuse and trash collection, and other utilities and services used on the Premises, all maintenance charges for
    utilities, and any storm sewer charges or other similar charges for utilities imposed upon the Premises by any Governmental Authority or utility provider, together with any taxes, penalties, surcharges or the like pertaining to Tenant&#8217;s use of the
    Premises. Landlord shall have no responsibilities whatsoever in connection with the foregoing. Electrical, gas (if any) and water shall be separately metered. Landlord may cause at Tenant&#8217;s expense for the actual cost thereof any utilities to be
    separately metered or charged directly to Tenant by the provider. Tenant shall pay its share of all charges for jointly metered utilities based upon consumption, as reasonably determined by Landlord. If any Governmental Authority suggests voluntary
    guidelines applicable to the Project, relating to the use or conservation of water, gas, electricity, power, or the reduction of automobile emissions, Landlord, at its sole but reasonable discretion to the extent voluntary, may comply with such
    voluntary guidelines and, accordingly, require Tenant to so comply. Landlord and Tenant shall comply with any mandatory controls imposed by any Governmental Authority.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall, at its sole cost and expense,
    contract directly with a janitorial service and shall pay for all janitorial services used on or for the Premises. Landlord shall have no obligations whatsoever in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall store all trash and garbage within the
    Premises or in a trash dumpster or similar container approved by Landlord as to type, location and screening, and Tenant shall arrange for the regular pick-up of such trash and garbage at Tenant&#8217;s expense. Tenant shall comply with applicable Laws
    related to trash and recycling.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.3.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font> Tenant shall, within ten&#160;(10) days after request
    by Landlord, provide consumption data in a form reasonably required by Landlord for: (i)&#160;any utility billed directly to Tenant or any subtenant or licensee of Tenant; and (ii)&#160;any sub metered or separately metered utility supplied to the Premises,
    which Landlord is not responsible for reading. If Tenant utilizes separate service providers from those of Landlord, Tenant hereby consents to Landlord obtaining the consumption data directly from such service providers and, within ten&#160;(10) days after
    written request, Tenant shall execute and deliver to Landlord and the service providers such written releases as the service providers may request evidencing Tenant&#8217;s consent to deliver the consumption data to Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.3.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant acknowledges (i) that Landlord shall have no
    obligation to provide any security measures for any portion of the Premises or the Project other than such commercially reasonable security measures employed by landlords of comparable Projects, in Landlord's sole discretion, and (ii) that Landlord has
    made no representation to Tenant regarding the safety or security of the Project. If Landlord provides any security measures at any time, then (a) Landlord shall not be obligated to continue providing such security measures, and Landlord shall not be
    obligated to provide such security measures with any particular standard of care, and (b) all reasonable and actual costs and expenses incurred by Landlord to implement such security measures will be considered Operating Expenses. Tenant assumes all
    responsibility for the security and safety of Tenant, the Premises, and/or Tenant&#8217;s Parties. Tenant may, at its own expense, install its own security system (&#8220;<b>Tenant&#8217;s Security System</b>&#8221;) in the Premises; provided, however, that Tenant shall
    coordinate the installation and operation of Tenant&#8217;s Security System as an Alteration, and Tenant shall coordinate with Landlord as reasonably requested by Landlord to ensure Landlord&#8217;s access to the Premises pursuant to its rights set forth in <u>Section&#160;6.5</u>
    above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">8.3.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except as otherwise specified herein, no failure to
    furnish or delay in furnishing any utilities or services or for diminution in the quality or quantity of any utilities shall result in the termination of this Lease or any liability of Landlord or any Landlord Party for loss or injury to persons or
    property, or for damages, fees, costs, or expenses of any kind whatsoever or injunctive relief; provided, however,&#160;in the event that Tenant requests Landlord&#8217;s assistance in restoring disrupted utility service, Landlord shall promptly cooperate with
    Tenant to assist Tenant to cause same to be restored, it being understood that any costs of same will be treated as Operating Expenses. Furthermore, Tenant will be entitled to an equitable abatement of Rent for the period of such failure or
    interruption (retroactive to the first day of such interruption) but only to the extent such failure or interruption: (i)&#160;is directly attributable to Landlord&#8217;s gross negligence or misconduct or that of its employees, agents or contractors, (ii)
    prevents Tenant from using, and Tenant does not use, the Premises or the affected portion thereof for the conduct of Tenant&#8217;s business operations therein, (iii) Tenant was using the Premises or such affected portion for the conduct of Tenant&#8217;s business
    operations prior to the failure or interruption, and (iv) such failure or interruption continues for more than three (3) consecutive business days (or ten (10) business days in any twelve (12)-month period) after delivery of written notice of such
    failure or interruption from Tenant to Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>9.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Insurance; Waiver
        of Subrogation</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">9.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Insurance</u>. Landlord shall purchase
    and keep in force a special causes of loss (all risk) property insurance policy covering the Premises. Landlord may also purchase and maintain such additional and commercially reasonable insurance coverage as Landlord may from time to time determine,
    taking into account what landlords of comparable buildings in comparable projects maintain, or as may be required by any Mortgagee, including commercial general liability insurance, pollution insurance in the amount of Five Million Dollars
    ($5,000,000), which pollution insurance shall not be placed until Tenant has commenced operations in the Premises, and insurance coverage against the risks of earthquake once the Landlord&#8217;s Work is complete, flood damage, terrorism or other perils, and
    business interruption coverage. All insurance carried by Landlord shall be in such amounts, issued by such companies, and on such terms and conditions as Landlord may from time to time determine, and the premiums and deductibles (not to exceed $25,000)
    for all insurance maintained by Landlord from time to time shall be included in Operating Expenses. Tenant shall, at its sole cost and expense, comply with any and all reasonable requirements pertaining to the Premises, the Building, and the Project of
    any insurer necessary for the maintenance of reasonable property and commercial general liability insurance covering the Building and the Project and the adjustment of any losses in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">9.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Insurance</u>. Tenant shall, at its own
    cost and expense, procure and keep in full force and effect for the Term:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Commercial General and Umbrella Liability
      Insurance</u>. Tenant shall maintain commercial general liability (CGL) and, if necessary, commercial umbrella insurance with a limit of not less than Five Million and No/100 Dollars ($5,000,000) each occurrence. CGL insurance shall be written on ISO
    occurrence form CG 00 01 4 13 (or a substitute form providing equivalent coverage) and shall cover liability arising from premises, operations, independent contractors, products-completed operations, personal injury and advertising injury, and
    liability assumed under an insured contract. Landlord and Landlord&#8217;s advisors, property managers, and any mortgagee of Landlord (&#8220;<b>Mortgagee</b>&#8221;) (collectively, including Landlord, the &#8220;<b>Landlord Insureds</b>&#8221;) shall be included as an insured
    under CGL, using ISO additional insured endorsement CG 20 11 or a substitute providing equivalent coverage, and under the commercial umbrella, if any. This insurance shall apply as primary insurance with respect to any other insurance or self-insurance
    programs afforded to Landlord. There shall be no endorsement or modification of the CGL to make it excess over other available insurance; alternatively, if the CGL states that it is excess or pro rata, the policy shall be endorsed to be primary with
    respect to the additional insured. A copy of the Additional Insured Endorsement or equivalent policy wording will be submitted with the Certificate of Insurance. If the required coverage is maintained by an excess/umbrella policy, the insurance shall
    be excess over and no less broad than all coverages described herein. The limit of any insurance shall not limit the liability of Tenant hereunder. Tenant waives all rights against Landlord and the Landlord Parties for recovery of damages to the extent
    these damages are covered by the commercial general liability or commercial umbrella liability insurance maintained pursuant to this Section. Such insurance shall contain a &#8220;contractual liability&#8221; endorsement insuring Tenant&#8217;s performance of Tenant&#8217;s
    obligation to indemnify Landlord and the Landlord Parties as set forth in this Lease. The amount and coverage of such insurance shall not limit Tenant&#8217;s liability nor relieve Tenant of any other obligation under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Commercial Property Insurance</u>. Tenant shall,
    at Tenant&#8217;s expense, maintain in full force and effect on all Tenant&#8217;s Work, Alterations and its business personal property, furniture, furnishings, trade or business fixtures, cabling, and equipment (collectively, &#8220;<b>Tenant&#8217;s Property</b>&#8221;) on the
    Premises, special causes of loss (all risk) property insurance in an amount equal to one hundred percent (100%) of the full replacement cost thereof and including coverage for sprinkler leakage. The policy shall be issued on ISO form CP 1030 or
    equivalent. Any coinsurance requirement in the policy shall be eliminated through the attachment of an agreed amount endorsement, the activation of an agreed value option, or as is otherwise appropriate under the particular policy form. During the Term
    of this Lease, the proceeds from any such insurance shall be used for the repair or replacement of Tenant&#8217;s Property. Landlord shall have no interest in the insurance upon Tenant&#8217;s Property and will sign all documents reasonably necessary in connection
    with the settlement of any claim or loss by Tenant respecting Tenant&#8217;s Property. Landlord will not carry insurance on Tenant&#8217;s Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Commercial Automobile Liability</u>. Tenant
    shall, at Tenant&#8217;s expense, maintain automobile liability insurance including coverage on owned, hired, and non-owned automobiles and other vehicles, if used in connection with the performance of the work, with bodily injury and property damage limits
    of not less than One Million and No/100 Dollars ($1,000,000.00) per accident. Tenant waives all rights against Landlord and the Landlord Parties for recovery of damages to the extent these damages are covered by the business auto liability or
    commercial umbrella liability insurance obtained by Tenant pursuant to this Section (or under any applicable auto physical damage coverage).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Workers&#8217; Compensation Insurance; Employer&#8217;s
      Liability Insurance</u>. Tenant shall, at Tenant&#8217;s expense, maintain workers&#8217; compensation and employer&#8217;s liability insurance. The employer&#8217;s liability limits shall not be less than One Million and No/100 Dollars ($1,000,000.00) each accident for
    bodily injury by accident or One Million and No/100 Dollars ($1,000,000.00) each employee for bodily injury by disease. Tenant waives all rights against Landlord and the Landlord Parties for recovery of damages to the extent these damages are covered
    by the workers&#8217; compensation and employer&#8217;s liability or commercial umbrella liability insurance obtained by Tenant pursuant to this Section. Tenant shall obtain an endorsement equivalent to WC 00 03 13 to effect this waiver.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Business Interruption Insurance</u>. Tenant
    shall, at Tenant&#8217;s expense, maintain in full force and effect business interruption, business income and extra expense or similar coverage as part of its commercial property insurance, and in no event shall Landlord be liable for any business
    interruption or other consequential loss sustained by Tenant, whether or not it is insured, even if such loss is caused by the negligence of Landlord, its employees, officers, directors, or agents.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Environmental Insurance</u>. Landlord also
    reserves the right to require Tenant to obtain insurance based on the Permitted Use, including without limitation, pollution legal liability insurance with a limit of Five Million and No/100 Dollars ($5,000,000), which pollution insurance will in no
    event be required to be in place until Tenant has commenced operations in the Premises, environmental impairment liability insurance and/or underground storage tank insurance, if Landlord deems such insurance necessary or appropriate based on Tenant&#8217;s
    Permitted Use or operations within the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">9.2.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font> <u>Builder&#8217;s Risk Insurance</u>. If required by
    Landlord in connection with the Tenant&#8217;s Work or any Tenant-made Alteration, Tenant shall obtain or shall cause its general contractor to maintain builder&#8217;s risk insurance for perils covered by a causes of loss-special form insurance policy for one
    hundred percent (100%) of the insurable value of all construction work in place or in progress from time to time.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">9.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>General Requirements; Evidence of Coverage</u>.
    All insurance policies required to be carried by Tenant under this Lease shall be issued by an insurance company qualified to do business in the state/commonwealth where the Premises are located for the issuance of such type of coverage and shall have
    a Best&#8217;s Financial Strength Rating of A- or better and a Best&#8217;s Financial Size Rating of VIII or better. Prior to Landlord granting access to the Premises to Tenant or any Tenant Party, Tenant shall deliver to Landlord certificates of insurance and
    true and complete copies of any and all endorsements required herein for all insurance required to be maintained by Tenant hereunder. Tenant shall, at least ten (10) days after expiration of each policy, furnish Landlord with certificates of renewal
    thereof. Failure of Landlord to demand such certificate or other evidence of full compliance with these insurance requirements or failure of Landlord to identify a deficiency from evidence that is provided shall not be construed as a waiver of Tenant&#8217;s
    obligation to maintain such insurance. Landlord may from time to time require reasonable increases in the types and/or limits of insurance to be carried by Tenant if Landlord believes that additional coverage is necessary or desirable. If Tenant does
    not comply with Tenant&#8217;s obligations under this <u>Section 9</u>, Landlord may, at its option and at Tenant&#8217;s expense, purchase such insurance coverage to protect Landlord Insureds. The cost of such insurance shall be paid to Landlord by Tenant, as
    Rent, within ten (10) days after demand.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">9.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Vendors&#8217; Insurance</u>. In addition to the
    insurance Tenant is required to carry under this Lease, Tenant acknowledges that Landlord will require Tenant&#8217;s vendors and contractors entering the Building to carry such insurance as Landlord shall reasonably determine to be necessary, and
    satisfactory evidence of such insurance must be delivered to Landlord prior to entry into the Building by such vendors and contractors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">9.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Mutual Waiver of Subrogation Rights</u>.&#160; Whenever
    (a) any loss, cost, damage, or expense resulting from fire, explosion, or any other casualty or occurrence is incurred by either of the parties to this Lease in connection with the Premises and (b) such party is then covered in whole or in part by
    insurance with respect to such loss, cost, damage, or expense, then the party so insured thereby releases the other party from any and all claims for damage, loss, or injury to its property it may have on account of such loss, cost, damage, or expense
    to the extent of any amount recovered by reason of such insurance and waives any right of subrogation which might otherwise exist in or accrue to any person on account thereof;&#160;provided&#160;that such release of and waiver of the right of subrogation shall
    not be operative in any case where the effect thereof is to invalidate such insurance coverage. The intent of this provision is that each party shall look solely to its insurance with respect to property damage or destruction which can be covered by
    property insurance of the type described in this&#160;<u>Section&#160;9.5</u>. Each party agrees that the property policies of insurance identified in this&#160;<u>Section 9</u>&#160;shall include a waiver of all rights of subrogation by the insurance carrier against the
    other party, its agents, and employees with respect to property damage covered by the applicable property insurance policy. Nothing in this <u>Section 9.5</u> shall relieve a party of liability to the other for failure to carry insurance required by
    this Lease.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>10.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Damages to
        Premises</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Repair Estimate</u>. If the Premises are damaged or
    destroyed by fire, earthquake or other casualty (a &#8220;<b>Casualty</b>&#8221;), Tenant shall give prompt written notice thereof to Landlord, and Landlord shall deliver to Tenant within a good faith estimate from a third party engineer or architect
    mutually-reasonably acceptable to Landlord and Tenant (the &#8220;<b>Damage Notice</b>&#8221;) of whether a material portion of the Premises (i.e., more than fifteen percent (15%) of the replacement cost thereof) has been damaged by the Casualty (a &#8220;<b>Material
      Casualty Event</b>&#8221;) and the time needed to repair the damage caused by such Casualty. Landlord shall use commercially reasonable efforts to cause the Damage Notice to be delivered within sixty (60) days after the parties have agreed upon a
    third-party engineer or architect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Rights</u>. If (i) the Damage Notice
    reflects that a Material Casualty Event has occurred and states that, in the professional opinion of such third party engineer or architect, such Material Casualty Event will take longer than three hundred sixty-five (365) days after the date of the
    Casualty to repair (the &#8220;<b>Repair Period</b>&#8221;), or (ii)&#160;Landlord fails to deliver the Damage Notice by the date that is ninety (90) days after such Casualty and thereafter fails to remedy such failure within ten (10) days after receipt of written
    notice from Tenant, then Tenant may terminate this Lease by delivering written notice to Landlord of its election to terminate within thirty (30) days after the Damage Notice has been delivered to Tenant (or, if no Damage Notice is delivered, within
    thirty (30) days after the expiration of the ten (10)-day period), with such termination effective as of the date of termination specified in such termination notice which shall in no event be earlier than thirty (30) days after the date of such
    termination notice, and no later than ninety (90) days after the date of such termination notice, to allow the parties sufficient time to comply with the provisions of this Lease regarding surrender of the Premises. Alternately, Tenant may, by delivery
    of written notice to Landlord with thirty (30) days after Tenant&#8217;s receipt of a Damage Notice reflecting a Material Casualty Event and Repair Period longer than three hundred sixty-five (365) days, elect to undertake the repair of such Casualty damage
    and restore the Premises at Tenant&#8217;s cost and expense;&#160;provided&#160;that Landlord shall reimburse Tenant an amount equal to the insurance proceeds actually received by Landlord in respect of such Casualty damage (or would have received if Landlord
    maintained the insurance required pursuant to the terms of this Lease, all as the same may have been reduced by amounts required to be paid towards deductibles and to Landlord&#8217;s current Mortgagee without the ability to use such proceeds towards the
    repair or restoration of the Premises). If Tenant elects to restore the Premises pursuant to the preceding sentence, such election shall be non-revocable, and such restoration shall become and be a Tenant obligation under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Rights</u>. If the Damage Notice
    reflects that a Material Casualty Event has occurred, a third-party engineer or architect estimates that the damage to the Premises cannot be repaired within the Repair Period, and Tenant does not elect to repair such Casualty damage pursuant to its
    right above, Landlord may terminate this Lease by giving written notice of its election to terminate within sixty (60) days after delivery of the Damage Notice to Tenant. Notwithstanding the foregoing, if the Premises are wholly or partially damaged or
    destroyed within the final nine (9) months of the then-applicable Term, and Tenant has not exercised Tenant&#8217;s renewal option pursuant to <u>Section 3</u> above, Landlord may, at its option, elect to terminate this Lease upon written notice given to
    Tenant within sixty (60) days following such Casualty (which termination shall be effective sixty (60) days after the giving of such notice to allow the parties sufficient time to comply with the provisions of this Lease regarding surrender of the
    Premises).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Repair Obligation</u>. If neither party elects to
    terminate this Lease following a Casualty and there has not been a Material Casualty Event, then Landlord shall, within a reasonable time after such Casualty, begin to repair the Premises and shall proceed with reasonable diligence to restore the
    Premises to substantially the same condition as existed immediately before such Casualty; however, Landlord&#8217;s obligation to repair or restore the Premises shall be limited to the extent of the insurance proceeds actually received by Landlord for the
    Casualty in question (or would have received if Landlord maintained the insurance required pursuant to the terms of this Lease, all as the same may have been reduced by amounts required to be paid to Landlord&#8217;s current Mortgagee without the ability to
    use such proceeds towards the repair or restoration of the Premises). Any deductible if and as accrued under Landlord&#8217;s insurance policies shall be deemed to be an Operating Expense hereunder. Notwithstanding any other provision of this Lease to the
    contrary but subject to then-applicable Laws, Landlord shall be required to reconstruct the Building and Premises in accordance with the Building standards for the initial construction and all of Landlord&#8217;s Work; provided however, under no
    circumstances shall Landlord be required to repair, replace or compensate Tenant or any other person for the repair, restoration or replacement of (i) Tenant&#8217;s Property, or (ii) any Leasehold Improvements (as defined below), and Tenant shall promptly
    repair and replace all such Leasehold Improvements at Tenant&#8217;s sole cost and expense. For purposes hereof, the &#8220;<b>Leasehold Improvements</b>&#8221; shall mean all tenant and other improvements in and to the Premises, including, without limitation, all TI
    Work, all Tenant&#8217;s Work, and all Alterations made in or to the Building and/or the Premises after the date of mutual execution and delivery of this Lease. In the event the damage is due to the gross negligence or willful misconduct of Landlord or any
    of Landlord Parties, Landlord shall be solely responsible for the full amount of the deductible for Tenant&#8217;s applicable insurance policies which shall not exceed $25,000, as well as for the full amount of the deductible for Landlord&#8217;s applicable
    insurance policies. Notwithstanding anything contained in this <u>Section&#160;10.4</u> to the contrary, if the Premises, Building or any other part of the Project are wholly or partially damaged or destroyed as a result of the gross negligence or willful
    misconduct of Tenant or any of Tenant&#8217;s agents, employees, customers, or contractors (individually a &#8220;<b>Tenant Party</b>&#8221; or &#8220;<b>Tenant Related Party</b>&#8221; and collectively, the &#8220;<b>Tenant Parties</b>&#8221; or &#8220;<b>Tenant Related Parties</b>&#8221;), Tenant shall
    pay to Landlord the full amount of the deductible under Landlord&#8217;s insurance policy and this Lease shall continue in full force and effect without any abatement or reduction in Rent or other payments owed by Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Abatement of Rent</u>. If the Premises are damaged
    by Casualty, Rent for the portion of the Premises in which Tenant is unable to conduct its business due to such damage, as determined by a third-party engineer or architect mutually-reasonably acceptable to Landlord and Tenant, shall be abated from the
    date of damage until (i) the completion of Landlord&#8217;s repairs (or until the date of termination of this Lease by Landlord or Tenant as provided above, as the case may be) or (ii) in the event Tenant elects to undertake the repairs pursuant to&#160;<u>Section&#160;10.3</u>,
    the earlier of (A) the completion of Tenant&#8217;s repairs and (B) the expiration of the Repair Period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">10.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Waiver</u>. The provisions of this&#160;<u>Section 10</u>&#160;shall







    constitute Tenant&#8217;s sole and exclusive remedy in the event of damage or destruction to the Premises, and Tenant waives and releases all statutory rights and remedies in favor of Tenant in the event of damage or destruction, including without limitation
    those available under California Civil Code Sections 1932 and 1933(4).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>11.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Condemnation</u></b>.
    If title to all or any portion of the Premises shall be taken by any public or quasi-public use or authority under any statute or by right of eminent domain, or by private purchase in lieu thereof, then the rights of the parties to share in the
    condemnation award or purchase price thereby resulting shall be governed by the provisions of this&#160;<u>Section 11</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Should all or such material portion of the Premises be taken in such a manner as to materially interfere with Tenant&#8217;s access to, use
    or occupancy thereof, Tenant shall have the right, at any time within sixty (60) days after the date possession of the condemned parcel is given to the condemnor, to terminate this Lease by giving Landlord written notice of such election prior to the
    expiration of such right, in which event this Lease shall terminate as of the date of such written notice, and all Rent shall be prorated to such date. Any determination of whether a taking results in a material interference with Tenant&#8217;s use and
    occupancy shall be made on the basis of a reasonable person, acting fairly and in good faith. Landlord shall be entitled to (i) any amount paid for the taking of Landlord&#8217;s fee interest in the Premises, (ii) any severance damages included in the award,
    (iii) any amount paid for the taking of the Premises except that paid for any improvements made to the Premises by Tenant which remain the property of Tenant, and (iv) any amount which represents the present worth of rent payments to be made in the
    future under the provisions of this Lease; and none of Landlord&#8217;s interests in the above shall be subject to any diminution or apportionment whatsoever. Tenant shall be entitled to compensation paid under condemnation for the taking of any improvements
    made to the Premises by Tenant which remain the property of Tenant and may, to the extent permitted by applicable Laws, pursue a claim against the condemnor for its moving expenses, inconvenience and business interruption in a proceeding independent of
    any suit pursued by Landlord so long as Landlord&#8217;s award is not thereby reduced or delayed or adversely affected, and Landlord is not at risk of incurring any liability or expense in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In the event of a partial taking of the Premises which does not materially interfere with Tenant&#8217;s continued use and occupancy of the
    Premises and there remains a sufficient portion of the Premises for the continued use of Tenant, then this Lease shall terminate only as to the part so taken, as of the date that possession of such part of the Premises is taken, and the Rent herein
    provided for shall be reduced to reflect the same proportion as the fair market rental value of the Premises after the taking bears to the fair market rental value of the Premises before the taking. In the event of a partial taking, Landlord agrees to
    replace or repair the Building facility constituting a portion of the Premises to its condition as existed when the Term commenced, and without regard to improvements made by Tenant, by reinstalling plumbing, electrical, wiring, walls, and paving, if
    necessary, so that such Building facility shall be completely operable and an integral whole, but at a cost to Landlord not to exceed the condemnation award received by Landlord. In the event of such partial taking, Landlord shall be entitled to
    receive all amounts described in the third sentence of paragraph (a) above; and none of Landlord&#8217;s interest in the above shall be subject to any diminution or apportionment whatsoever. Tenant shall be entitled to compensation paid under any partial
    taking for the taking of any improvements made to the Premises by Tenant which remain the property of Tenant.</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Landlord and Tenant agree to execute all documents and assignments reasonably necessary to carry out this&#160;<u>Section 11</u>&#160;in the
    event of condemnation or purchase in lieu thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant hereby waives any and all rights it might otherwise have pursuant to Section&#160;1265.130 of The California Code of Civil Procedure,
    and any other Laws which allow it to petition a Governmental Authority to terminate the Lease in the event of a partial taking or taking of the Premises, the Building, the Project, or any portion thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>12.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Assignment and
        Subletting</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">12.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Transfer</u>. Except as set forth below, Tenant
    shall not, without Landlord&#8217;s prior written consent (which consent shall not be unreasonably withheld, conditioned or delayed), voluntarily or by operation of law, directly or indirectly, mortgage, pledge, assign or encumber this Lease or any interest
    herein, including, but not limited to, the right to initiate any collections, lawsuits, audits or other findings of fact, sublease any portion of the Premises or any right or privilege appurtenant thereto, or grant any license or right to use any
    portion of the Premises (each, a &#8220;<b>Transfer</b>&#8221;). Notwithstanding the foregoing, subject to the terms and conditions hereof except that Landlord&#8217;s consent shall not be required, Tenant may at any time assign this Lease (or sublet all or any portion
    of the Premises) to any of the following (as the case may be, a &#8220;<b>Permitted Transfer(s)</b>&#8221;): (i)&#160;any Affiliate (as defined below) of Tenant, (ii) a successor to Tenant by merger or consolidation, or (iii)&#160;a successor to Tenant by purchase of all or
    substantially all (i.e., at least ninety percent (90%) of Tenant&#8217;s assets; provided, however, that, as to any Permitted Transfer, the proposed transferee has a net worth (as determined in accordance with GAAP, but excluding intellectual property and
    any other intangible assets (&#8220;<font style="font-family: Times New Roman, Times, Serif"><b>Net Worth</b><font style="font-weight: normal">&#8221;</font></font>)) immediately after the transfer that is not less than Tenant&#8217;s Net Worth immediately before the
    transfer or as otherwise approved in writing by Landlord. Subject to the foregoing, this Lease shall be binding upon, inure to the benefit of, and be enforceable by the parties and their respective successors and permitted assigns. For purposes of this
    Lease, &#8220;<b>Affiliate(s)</b>&#8221; means, as to either party, any other individual or entity that, directly or indirectly, controls, or is controlled by, or is under common control with, such party. For this purpose, &#8220;control&#8221; (including, with its
    correlative meanings, &#8220;controlled by&#8221; and &#8220;under common control with&#8221;) shall mean the ownership of more than fifty percent (50%) of the voting stock of a corporation or more than fifty percent (50%) of all of the legal and equitable interests in any
    other business entity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">12.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requirements for Transfer</u>. If Tenant desires to
    effect a Transfer, including a Permitted Transfer, then at least thirty (30) days before the date Tenant desires the Transfer to be effective (the &#8220;<b>Transfer Date</b>&#8221;), Tenant shall give Landlord a notice (the &#8220;<b>Transfer Notice</b>&#8221;) containing
    such information about the proposed transferee, including the proposed use of the Premises and any Hazardous Materials proposed to be used, stored, handled, treated, generated in, released or disposed of from the Premises, the Transfer Date, any
    relationship between Tenant and the proposed transferee, and all material terms and conditions of the proposed Transfer, including a copy of any proposed assignment or sublease in its final form, and such other information as is reasonably necessary or
    appropriate for Landlord to consider whether to grant its consent. If Landlord&#8217;s consent is required, Landlord may, by giving written notice to Tenant within ten (10) business days after receipt of the Transfer Notice: (i) grant such consent, (ii)
    refuse such consent, in its reasonable discretion and provide a detailed explanation as to its reasons therefor, or (iii)&#160;terminate this Lease with respect to the space described in the Transfer Notice (a &#8220;<b>Transfer Termination</b>&#8221;). If Landlord
    delivers notice of its election to exercise a Transfer Termination, Tenant shall have the right to withdraw such Transfer Notice by giving written notice to Landlord of such election within five (5) business days after its receipt of notice of the
    Transfer Termination. If Tenant withdraws such Transfer Notice, this Lease shall continue in full force and effect. If Tenant does not withdraw such Transfer Notice, this Lease, and the term and estate herein granted, shall terminate as of the date set
    forth in the notice of Transfer Termination with respect to the space described in such Transfer Notice. No failure of Landlord to exercise any such option to terminate this Lease, or to deliver a timely notice in response to the Transfer Notice, shall
    be deemed to be Landlord&#8217;s consent to the proposed Transfer. Tenant shall pay Landlord&#8217;s reasonable fees (including, but not limited to, the fees and expenses of Landlord&#8217;s counsel) actually incurred in connection with Landlord&#8217;s consideration of any
    Transfer and/or its preparation or review of any documents in connection therewith. If Landlord shall consent to, or reasonably withhold its consent to, any proposed Transfer, Tenant shall indemnify, defend, and hold harmless Landlord against and from
    any and all loss, liability, damages, costs, and expenses (including reasonable counsel fees and expenses) resulting from any claims that may be made against Landlord by the proposed transferee or by any brokers or other persons claiming a commission
    or similar fee in connection with the proposed Transfer. Notwithstanding the foregoing or anything to the contrary in this Lease, if Tenant is prohibited from providing a Transfer Notice as to any Permitted Transfer as a result of government
    regulations, Tenant shall provide notice as soon as reasonably practical after the Transfer Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">36</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">12.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Conditions to Transfer</u>. As a condition to any
    Transfer, whether or not Landlord&#8217;s consent is required, Landlord may require:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">12.3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>that any proposed transferee agree in writing at the
    time of such Transfer that if Landlord gives such party notice that Tenant is in default under this Lease, such party shall thereafter make all payments otherwise due Tenant directly to Landlord, which payments will be received by Landlord without any
    liability except to credit such payment against those due under the Lease, and any such third party shall agree to attorn to Landlord or its successors and assigns should this Lease be terminated for any reason;&#160;provided,&#160;however, in no event shall
    Landlord or its successors or assigns be obligated to accept such attornment;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">12.3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>a list of Hazardous Materials, certified by the
    proposed transferee to be true and correct, which the proposed transferee intends to use, store, handle, treat, generate in, or release or dispose of from the Premises, together with copies of all Haz Mat Documents relating to such use, storage,
    handling, treatment, generation, Release, or disposal of Hazardous Materials by the proposed transferee in, on, under, or about the Premises. Neither Tenant nor any such proposed transferee is required, however, to provide Landlord with any portion(s)
    of such documents containing information of a proprietary nature which, in and of themselves, do not contain a reference to any Hazardous Materials or hazardous activities; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">12.3.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>that the proposed transferee certifies in writing that
    it can and does make the representations, warranties, and certifications set forth in <u>Section&#160;35</u>, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">12.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Release</u>. No Transfer, nor Landlord consent
    to any Transfer, shall relieve Tenant or any transferee from obtaining the consent of Landlord to any further Transfer, nor shall it release Tenant or any transferee from full and primary liability under this Lease. The acceptance of Rent hereunder, or
    the acceptance of performance of any other term, covenant, or condition thereof, from any other person or entity shall not be deemed to be a waiver of any of the provisions of this Lease or a consent to any Transfer of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">12.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Transfer Premium</u>. If Landlord approves a
    Transfer, Tenant shall pay to Landlord, as Rent, fifty percent (50%) of any Transfer Premium received by Tenant. The term &#8220;<b>Transfer Premium</b>&#8221; means all Rent and other consideration paid by a transferee in excess of the Rent payable by Tenant
    under this Lease (on a rentable square foot basis, if less than the entire Premises is transferred), after deducting Transfer Costs. As used herein, &#8220;<b>Transfer Costs</b>&#8221; means the actual costs incurred and paid by Tenant for (i)&#160;any third-party
    leasing commissions that are reasonable and customary for the market in which the Premises are located, (ii)&#160;any tenant improvement allowance actually paid by Tenant to the transferee for improvements made in the Premises, and (iii) out-of-pocket legal
    fees, concessions, allowances, or reletting fees and expenses reasonably incurred by Tenant in connection with such Transfer. For purposes of the foregoing calculation, the leasing commissions and any tenant improvement allowance shall be amortized on
    a straight-line basis over the term of the applicable Transfer. If part of the consideration for such Transfer shall be payable other than in cash, Landlord&#8217;s share of such non-cash consideration shall be in such form as is reasonably satisfactory to
    Landlord. If Tenant shall enter into multiple Transfers, the Transfer Premium shall be calculated independently with respect to each Transfer. The Transfer Premium due Landlord hereunder shall be earned and paid monthly, within five&#160;(5) days after
    Tenant receives any Transfer Premium from the transferee. Landlord shall have the right to request, and Tenant shall promptly provide, sufficient documentation to confirm the accurate Transfer Premium due in connection with any Transfer. If Landlord is
    unable to verify the accuracy of the Transfer Premium, Landlord shall have the right at all reasonable times to audit the books, records, and papers of Tenant relating to such Transfer and to make copies thereof. If any Transfer Premium is found to be
    understated, Tenant shall within thirty&#160;(30) days after demand pay the deficiency, and if understated by more than two percent (2%), Tenant shall pay Landlord&#8217;s costs of such audit. The Transfer agreement between Tenant and the transferee, after
    approval by Landlord, shall not be amended or terminated without Landlord&#8217;s prior written consent. In the event that, notwithstanding the giving of such notice, Tenant collects any rent or other sums from the transferee, then Tenant shall hold such
    sums in trust for the benefit of Landlord and shall immediately forward the same to Landlord. Landlord&#8217;s collection of such rent and other sums shall not constitute an acceptance by Landlord of attornment by such assignee or subtenant. The provisions
    of this <u>Section 12.5</u> shall not apply to Permitted Transfers.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>13.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Signs and Fixtures</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">13.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Signs</u>. Tenant shall not erect any type or size
    of sign or signs (including electric or gas signs) on the roof or on the walls of the Building without the prior written consent of Landlord, which Landlord shall not unreasonably withhold, condition or delay; provided, however, Tenant shall have the
    right to erect, maintain and operate Building and monument signage bearing the corporate name, logo or other trademarks of Tenant reasonably acceptable to Landlord. Landlord and Tenant hereby approve the proposed signage attached hereto as <u>Exhibit&#160;D</u>.
    Any such signage which is approved by Landlord or otherwise permitted to be erected, maintained and operated pursuant to this&#160;<u>Section 13.1</u>&#160;shall be erected, maintained and operated by Tenant, at its sole cost and expense, in compliance with all
    applicable Laws, Rules, and Governing Documents.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">13.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Fixtures</u>. Subject to&#160;<u>Section 7</u>&#160;above,
    Tenant shall also have the right to install any equipment or trade fixtures required in the operation of its business, which such equipment or trade fixtures shall be deemed Tenant&#8217;s Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>14.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Waivers</u></b>.
    Any agreement on the part of Tenant or Landlord to extend the time for the performance of any of the obligations or other acts of the other party to this Lease shall be valid only if set forth in an instrument in writing signed on behalf of such party.
    The failure or delay of Tenant or Landlord to assert any of its rights under this Lease or otherwise shall not constitute a waiver of such rights, nor shall any single or partial exercise by Tenant or Landlord of any of its rights under this Lease
    preclude any other or further exercise of such rights or any other rights under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>15.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Quiet Enjoyment and
        Impairment of Use</u></b>. Landlord covenants that, subject to all matters of record encumbering the Premises, Tenant, upon payment of Rent and performance of its undertakings herein specified, shall and may peacefully and quietly have, hold, and
    enjoy the Premises for the Term, with all the rights and privileges and for the uses herein provided, and Landlord acknowledges and agrees that this covenant is a covenant running with the land and is an integral part of Tenant&#8217;s leasehold estate in
    the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>16.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Tenant&#8217;s Self-Help
        Rights</u></b>. Notwithstanding any provision set forth in this Lease to the contrary, if at any time (a) Tenant provides prior written notice to Landlord of an event or circumstance that requires the action of Landlord with respect to repair
    and/or maintenance, (b)&#160;Landlord is, in fact, required to perform repairs and/or maintenance under the terms of this Lease or is otherwise in default, and (c) Landlord fails to commence such action within a reasonable period of time (given the
    circumstances) after the receipt of such written notice, but in any event not later than seven (7) business days after receipt of such written notice (or within two&#160;(2) business days in the case of an emergency) (provided that, for purposes of this&#160;<u>Section







      16</u>, to &#8220;commence&#8221; such action includes any steps taken by Landlord to design, consult, bid or seek permits or other governmental approval in connection with the necessary work so long as Landlord thereafter diligently continues the cure in good
    faith), then Tenant, as its sole remedy, may proceed to take the required action and shall be entitled to reimbursement by Landlord of Tenant&#8217;s reasonable and necessary, actual out-of-pocket costs and expenses in taking such action (and only such
    action as specified in the notice given to Landlord). Such amounts shall be reimbursed by Landlord within thirty (30) days after receipt from Tenant of a detailed invoice setting forth a breakdown of the costs and expenses incurred in connection with
    the action taken by Tenant. If Landlord fails to reimburse Tenant for such costs within the aforesaid thirty&#160;(30)-day period, Tenant shall have the right to offset such amounts against the next installments of Rent that become due and owing. If Tenant
    takes such action, and such work affects the Building Structure, then Tenant shall use only those contractors used by Landlord in the Building for work thereon. In the event Landlord fails to comply with any of Landlord&#8217;s other obligations under this
    Lease within a reasonable time period not to exceed thirty (30) days after Tenant furnishes Landlord with written notice of such breach or failure (or such longer period of time as may be reasonably necessary to effect such cure, provided that Landlord
    promptly commences such cure within the thirty (30)-day period and diligently prosecutes such cure to completion), Tenant shall have the right, but not the obligation, to perform such obligation on Landlord&#8217;s account and Landlord shall reimburse Tenant
    within thirty (30) days of written demand (with underlying documentation) for the amount reasonably and actually expended by Tenant to perform such obligation.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Tenant shall give to any Mortgagee a copy of any notice of default given to Landlord at the same time as such notice is given to Landlord, provided that prior to such
    notice Tenant has been notified, in writing, of the address of such Mortgagee. Except as otherwise set forth in any subordination and non-disturbance agreement between Tenant and a Mortgagee, Tenant will not seek to terminate this Lease by reason of
    any act or omission that constitutes (or would over time constitute) a default of Landlord until Tenant shall have given written notice of such act or omission to Mortgagee (at Mortgagee&#8217;s last address furnished to Tenant) and until a period of thirty
    (30) days shall have elapsed, Mortgagee shall have the right, but not the obligation, to remedy such act or omission; provided however, that if the act or omission does not involve the payment of money from Landlord to Tenant and (i)&#160;is of such a
    nature that it could not be reasonably remedied within the thirty (30) day-period aforesaid, or (ii)&#160;the nature of the act or omission or the requirements of local law require Mortgagee to appoint a receiver or to foreclose on or commence legal
    proceedings to recover possession of the Property in order to effect such remedy and such legal proceedings and consequent remedy cannot reasonably be achieved within said thirty (30) days, then Mortgagee shall have such further time as is reasonable
    under the circumstances to effect such remedy (not to exceed forty five (45) days after the expiration of the thirty (30) day-period aforesaid) provided that Mortgagee shall notify Tenant, within ten (10) days after receipt of Tenant&#8217;s notice, of
    Mortgagee&#8217;s intention to effect such remedy and provided further that Mortgagee institutes immediate legal proceedings to appoint a receiver for the Premises or to foreclose on or recover possession of the Premises within said thirty (30) day-period
    and thereafter prosecutes said proceedings and remedy with due diligence and continuity to completion. Notwithstanding the foregoing, Mortgagee shall have no rights under this <u>Section&#160;16</u> if Mortgagee is an entity that controls, is controlled
    by, or is under common control with Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>17.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Events of Default;
        Remedies</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">17.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Events of Default</u>. Tenant shall be considered
    to be in default of this Lease upon the occurrence of any of the following events of default, following the expiration of each applicable notice and cure period (each, an &#8220;<b>Event of Default</b>&#8221;):</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Tenant&#8217;s failure to pay when due all or any portion of
    the Rent; provided, however, that Landlord will give Tenant written notice and an opportunity to cure any failure to pay Rent within five (5) business days of any such notice not more than once in any twelve (12)-month period and Tenant agrees that
    such notice shall be in lieu of and not in addition to, or shall be deemed to be, any notice required by law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Tenant fails to pay and release of record, or
    diligently contest and bond around, any mechanic&#8217;s or construction lien filed against the Premises for any work performed, materials furnished, or obligation incurred by or at the request of Tenant, within thirty&#160;(30) days of Tenant&#8217;s receipt of
    written notice of attachment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">40</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>To the extent permitted by applicable Laws, (A)&#160;Tenant
    or any guarantor of this Lease being placed into receivership or conservatorship, or becoming subject to similar proceedings under Federal or State Law, or (B)&#160;a general assignment by Tenant or any guarantor of this Lease for the benefit of creditors,
    or (C)&#160;the filing by or against Tenant or any guarantor of this Lease of any proceeding under an insolvency or bankruptcy law, unless in the case of such a proceeding filed against Tenant or any guarantor the same is dismissed within ninety (90) days,
    or (D)&#160;the appointment of a trustee or receiver to take possession of all or substantially all of the assets of Tenant or any guarantor of this Lease, unless possession is restored to Tenant or such guarantor within thirty (30) days, or (E)&#160;any
    execution or other judicially-authorized seizure of all or substantially all of Tenant&#8217;s assets located upon the Premises or of Tenant&#8217;s interest in this Lease, unless such seizure is discharged within thirty (30) days.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Abandonment pursuant to the terms of California Civil
    Code Section 1951.3 of the Premises by Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Tenant fails to maintain the insurance coverages to
    the extent required under&#160;<u>Section 9</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>The failure by Tenant or any guarantor to maintain its
    legal existence if the failure is not cured within seven (7) business days after written notice is delivered to Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Failure of Tenant to execute and deliver to Landlord
    any estoppel certificate, subordination agreement, or lease amendment within the time periods and in the manner required by this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.8<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>A Transfer in violation of <u>Section 12</u> above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.1.9<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Tenant&#8217;s failure to comply in all material respects
    with any other term, provision or covenant of this Lease not enumerated in Sections <u>17.1.1</u> through <u>17.1.8</u>, above, if the failure is not cured within thirty (30) days after written notice is delivered to Tenant, unless any such term,
    provision or covenant has a specified cure period set forth elsewhere in this Lease, in which case such specific cure period and not the thirty (30)-day period specified in this Section&#160;<u>17.1.9</u> shall apply thereto. If any failure to comply
    described in this Section <u>17.1.9</u> cannot reasonably be cured within thirty (30) days, Tenant shall be allowed additional time as is reasonably necessary to cure the failure so long as: (1)&#160;Tenant commences to cure the failure within thirty (30)
    days, and (2)&#160;Tenant diligently and continuously pursues a course of action to cure the failure and bring Tenant back into compliance with this Lease. Notwithstanding the foregoing, if Tenant&#8217;s failure to comply creates a hazardous condition, or
    imminent risk of injury to persons or property, the failure must be cured promptly upon written notice thereof to Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">The notice periods provided herein are in lieu of, and not in addition to, any notice periods provided by Law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">41</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">17.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Remedies</u>. Upon the occurrence of any Event of
    Default, Landlord shall have the option to pursue any one or more of the following remedies (and in connection therewith Tenant hereby specifically waives notice and demand for payment of Rent or other obligations, including without limitation,
    pursuant to California Code of Civil Procedure Section 1161, and waives any and all other notices or demand requirements imposed by applicable Law, in each case except for those notices and demands required pursuant to the terms of this&#160;<u>Section 17</u>):</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Terminate this Lease and Tenant&#8217;s right to possession
    of the Premises and recover from Tenant an award of damages equal to the sum of the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Worth at the Time of Award (as defined
    below) of the unpaid Rent which had been earned at the time of termination;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Worth at the Time of Award of the amount
    by which the unpaid Rent that would have been earned after termination until the time of award exceeds the amount of such Rent loss that Tenant affirmatively proves could have been reasonably avoided using commercially reasonable efforts and any
    amounts actually received during such period from others to whom the Premises may be rented;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Worth at the Time of Award of the amount
    by which the unpaid Rent for the balance of the Term after the time of award exceeds the amount of such Rent loss that Tenant affirmatively proves could be reasonably avoided using commercially reasonable efforts;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Any other amount necessary to compensate
    Landlord for all the detriment proximately caused by Tenant&#8217;s failure to perform its obligations under this Lease or which in the ordinary course of things would be likely to result therefrom, including, but not limited to: (A) any costs or expenses
    incurred by Landlord (1) in retaking possession of the Premises; (2) in maintaining, repairing, preserving, restoring, replacing, cleaning, altering, remodeling or rehabilitating the Premises or any affected portions of the Building or the Project,
    including such actions undertaken in connection with the reletting or attempted reletting of the Premises to a new tenant or tenants; (3) for leasing commissions, advertising costs and other expenses of reletting the Premises; or (4) in carrying the
    Premises, including taxes, insurance premiums, utilities and security costs; (B) any unearned brokerage commissions paid in connection with this Lease; (C) reimbursement of any previously-waived or abated Base Rent or Rent or any free rent or reduced
    rent granted hereunder; and (D) any concession made or paid by Landlord for the benefit of Tenant including, but not limited to, any moving allowances, contributions, payments or loans by Landlord for tenant improvements or build-out allowances
    (including, but not limited to, any unamortized portion of the Allowance (as defined in Section 6 of the Work Letter);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Such reasonable attorneys&#8217; fees and expenses
    incurred by Landlord as a result of such Event of Default, and court costs in the event suit is filed by Landlord to enforce such remedy; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">42</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">17.2.1.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>At Landlord&#8217;s election, such other amounts in
    addition to or in lieu of the foregoing as may be permitted from time to time by applicable law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">The &#8220;<b>Worth at the Time of Award</b>&#8221; as to the amounts referred to in <u>Sections 17.2.1.1</u> and <u>17.2.1.2</u> above, shall be computed by allowing interest
    on the amount determined pursuant to such Sections at the Default Rate. For purposes of <u>Section 17.2.1.3</u>, the Worth at the Time of Award shall be computed by discounting the amount determined pursuant to such section to present worth at a
    discount rate equal to one percentage point above the discount rate then in effect at the Federal Reserve Bank of San Francisco. For purposes hereof, the &#8220;<b>Default Rate</b>&#8221; shall be the lesser of a per annum rate equal to:&#160;(i)&#160;the greatest per annum
    rate of interest permitted from time to time under applicable law, or (ii)&#160;the Prime Rate plus five percent (5%) (the &#8220;<b>Default Rate</b>&#8221;). For purposes hereof, the &#8220;<b>Prime Rate</b>&#8221; shall be the per annum interest rate publicly announced as its
    prime or base rate by a federally insured bank selected by Landlord in the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.2.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>&#160;Employ the remedy described in California Civil Code
    &#167;&#160;1951.4 (Landlord may continue this Lease in effect after Tenant&#8217;s breach and abandonment and recover Rent as it becomes due, if Tenant has the right to sublet or assign, subject only to reasonable limitations). Landlord shall not be liable in any way
    whatsoever for its failure or refusal to relet the Premises. For purposes of this Section 17.2.2, the following acts by Landlord will not constitute the termination of Tenant&#8217;s right to possession of the Premises:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">(A)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Acts of maintenance or preservation or efforts to relet the Premises, including, but not limited to, alterations, remodeling,
    redecorating, repairs, replacements and/or painting as Landlord shall consider advisable for the purpose of reletting the Premises or any part thereof, or</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 148.5pt">(B)&#160;&#160;&#160;&#160;&#160;&#160;&#160;The appointment of a receiver upon the initiative of Landlord to protect Landlord&#8217;s interest under this Lease or in the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 148.5pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.2.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>With or without terminating this Lease, in compliance
    with applicable Laws, re-enter the Premises, by force if necessary, and remove all persons and property from the Premises; such property may be removed and stored in a public warehouse or elsewhere at the cost of and for the account of Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.2.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>In connection with any Event of Default, perform any
    such term, provision, covenant, or condition, or make any such payment which is the subject of such Event of Default, and by doing so Landlord shall not be liable or responsible for any loss or damage thereby sustained by Tenant or anyone holding under
    or through Tenant or any Tenant Parties. If Landlord performs any of Tenant&#8217;s obligations hereunder, the full amount of the cost and expense incurred or the payment so made or the amount of the loss so sustained shall immediately be owing by Tenant to
    Landlord, and Tenant shall pay to Landlord within thirty&#160;(30) days after demand, as Rent, the full amount thereof with interest thereon at the Default Rate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">17.2.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>In the event of the abandonment of the Premises by
    Tenant or if Landlord elects to re-enter as provided in <u>Section&#160;17.2.3</u> above, or takes possession of the Premises pursuant to (i) legal proceeding or (ii) any notice provided by Law, then (if Landlord does not elect to terminate this Lease as
    provided in <u>Section 17.2.1)</u> above, Landlord may from time to time, without terminating this Lease, relet the Premises or any part thereof for such term or terms and at such rental or rentals and upon such other terms and conditions as Landlord
    in its sole but reasonable discretion may deem advisable with the right to make alterations and repairs to the Premises in Landlord&#8217;s sole discretion. If Landlord elects to so relet, then rentals received by Landlord from such reletting shall be
    applied in the following order: (1) to reasonable attorneys&#8217; fees and expenses incurred by Landlord as a result of an Event of Default and court costs in the event suit is filed by Landlord to enforce such remedies; (2) to the payment of any
    indebtedness other than Rent due hereunder from Tenant to Landlord; (3) to the payment of any costs of such reletting; (4)&#160;to the payment of the costs of any alterations and repairs to the Premises; (5) to the payment of Rent due and unpaid hereunder;
    and (6) the residual amount, if any, shall be held by Landlord and applied in payment of future Rent and other sums payable by Tenant hereunder as the same may become due and payable hereunder. If the portion of such rentals received from such
    reletting during any month, which is applied to the payment of Rent hereunder, is less than the Rent payable during the month by Tenant hereunder, then Tenant shall pay such deficiency to Landlord. Such deficiency shall be calculated and paid monthly.
    Tenant shall also pay to Landlord, as soon as ascertained, any commercially reasonable and actual costs and expenses, taking into consideration market conditions and standard concessions being offered, incurred by Landlord in such reletting or in
    making such alterations and repairs not covered by the rentals received from such reletting. No re-entry or taking of possession of the Premises by Landlord pursuant to this <u>Section 17</u> shall be construed as an election to terminate this Lease
    unless a written notice of such intention is given to Tenant or unless the termination thereof is decreed by a court of competent jurisdiction. Notwithstanding any reletting without termination by Landlord because of any Event of Default by Tenant,
    Landlord may at any time after such reletting elect to terminate this Lease for any such Event of Default.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">43</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">17.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>WAIVERS</u>. TENANT HEREBY WAIVES ANY AND ALL
    RIGHTS CONFERRED BY SECTION&#160;3275 OF THE CIVIL CODE OF CALIFORNIA AND BY SECTIONS&#160;1174 (c) AND 1179 OF THE CODE OF CIVIL PROCEDURE OF CALIFORNIA AND ANY AND ALL OTHER LAWS AND RULES OF LAW FROM TIME TO TIME IN EFFECT DURING THE TERM PROVIDING THAT
    TENANT SHALL HAVE ANY RIGHT TO REDEEM, REINSTATE OR RESTORE THIS LEASE FOLLOWING ITS TERMINATION PURSUANT TO THIS&#160;<u>SECTION 17</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">17.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Other Rights and Remedies</u>. If Tenant is in an
    Event of Default, then, to the extent permitted by Law, Landlord shall be entitled to receive interest on any unpaid item of Rent at the Default Rate. No right or remedy herein conferred upon or reserved to any party to this Lease is intended to be
    exclusive of any other right or remedy, and each and every right and remedy shall be cumulative. No act or conduct of Landlord, whether consisting of the acceptance of the keys to the Premises, or otherwise, shall be deemed to be or constitute an
    acceptance of the surrender of the Premises by Tenant prior to the expiration of the Term, and such acceptance by Landlord of surrender by Tenant shall only be effective upon a written acknowledgment of acceptance of surrender signed by Landlord. The
    surrender of this Lease by Tenant, voluntarily or otherwise, shall not work in a merger unless Landlord elects in writing that such merger take place, but shall operate as an assignment to Landlord of any and all existing subleases, or Landlord may, at
    its option, elect in writing to treat such surrender as a merger terminating Tenant&#8217;s estate under this Lease, and thereupon Landlord may terminate any or all such subleases by notifying the subtenant of its election to do so within five&#160;(5) business
    days after such surrender.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">44</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>18.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Subordination;
        Attornment</u></b>. Landlord represents and warrants that there is no current Mortgagee. As a condition to Tenant&#8217;s subordination for all future Mortgagees, Landlord will secure for and promptly deliver to Tenant a non-disturbance agreement on such
    future Mortgagee&#8217;s commercially reasonable standard form, which shall provide that, in the event Tenant is not in a default beyond applicable notice and cure periods, Mortgagee will not disturb the terms of the Lease, including without limitation the
    covenant to complete the required construction, to fund Tenant&#8217;s allowance, and will not disturb the termination rights, self-help rights, rights of expansion and purchase rights as set forth in the Lease, and otherwise subject to approval by Tenant in
    its reasonable discretion. If Landlord requests Tenant's review of any non-disturbance agreement as to a future Mortgagee Tenant will provide its approval or disapproval (with detailed reasons therefor and reasonably changes to such form) within
    fifteen (15) business days after receipt of such request. Subject to the foregoing, Tenant accepts this Lease subject and subordinate to any mortgage(s), deed(s) of trust, ground lease(s) or other lien(s) or encumbrances now or subsequently arising
    upon the Premises, the Building, or the Project, and to renewals, modifications, refinancings and extensions thereof (collectively referred to as a &#8220;<b>Mortgage</b>&#8221;). This clause shall be self-operative except as provided above, but upon request from
    a Mortgagee, in lieu of having the Mortgage be superior to this Lease, a Mortgagee shall have the right at any time to subordinate its Mortgage to this Lease. If, in connection with obtaining financing for the Project or any portion thereof, any
    Mortgagee shall request reasonable modifications to this Lease as a condition to such financing, Tenant shall not unreasonably withhold, condition, or delay its consent to such modifications, provided such modifications do not, in Tenant&#8217;s reasonable
    discretion, adversely affect Tenant&#8217;s rights or increase Tenant&#8217;s obligations under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>19.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Surrender of
        Premises</u></b>. At the expiration or earlier termination of this Lease or Tenant&#8217;s right of possession, Tenant shall remove Tenant&#8217;s property, including without limitation, its business personal property, furniture, furnishings, trade or business
    fixtures, cabling, and equipment, from the Premises and all signs installed by or on behalf of Tenant within the Project, and shall quit and surrender the Premises to Landlord in the same condition as existing on the Lease Commencement Date, free of
    Hazardous Materials not existing as of the Lease Commencement Date, broom clean, and in good order, condition and repair, ordinary wear and tear and Casualty excepted. Normal wear and tear shall not include any damage or deterioration to the floors of
    the Premises arising from the use of forklifts in, on or about the Premises (including any marks or stains on any portion of the floors), and any damage or deterioration that would have been prevented by proper maintenance by Tenant or Tenant otherwise
    performing all of its obligations under this Lease. In addition, Tenant shall remove and restore (1) any improvements and equipment located in the manufacturing portions of the Premises, (2) the chemical facility at the rear of the Building and any and
    all pipes connected thereto, and (3) upon written request from Landlord received not less than one hundred twenty (120) days prior to the expiration or earlier termination of the Lease, the HVAC mezzanine equipment, all as set forth on <b><u>Exhibit G</u></b>
    attached hereto. Tenant&#8217;s removal and disposal work must comply with the Building&#8217;s Sustainability Practices and the applicable Green Building Standards, if any. Tenant shall pay for or reimburse Landlord, as applicable, for any damage, expense or loss
    suffered by Landlord in connection with Tenant&#8217;s removal work pursuant to this <u>Section 19</u>. If Tenant fails to completely satisfy its removal and restoration obligations by the expiration of the Term (or within thirty (30) days after the earlier
    termination of this Lease or of Tenant&#8217;s right to possession), Landlord, at Tenant&#8217;s sole cost and expense, shall be entitled (but not obligated) to cause such removal work to be done and to remove and store Tenant&#8217;s property. Landlord shall not be
    responsible for the value, preservation, or safekeeping of Tenant&#8217;s property. Tenant shall pay Landlord, upon demand, all of Landlord&#8217;s costs and expenses to conduct such removal work and the expenses and storage charges incurred for Tenant&#8217;s property.
    Alternately, Landlord may deem all or any part of Tenant&#8217;s property to be abandoned, and title to Tenant&#8217;s property shall be deemed to be immediately vested in Landlord. Tenant waives the provisions of California Civil Code Sections&#160;1980 <i>et seq.</i>
    and 1993, <i>et seq.</i> governing the disposal of lost or abandoned property and releases Landlord, its employees, and agents from any and all claims, damages, liabilities and actions of every kind and nature whatsoever, whether now known or unknown,
    arising out of or relating to disposal of Tenant&#8217;s property remaining in the Premises after the end of the Term.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">45</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">At least four (4) months prior to the surrender of the Premises, Tenant shall deliver to Landlord a narrative description of the actions proposed
    (or required by any Governmental Authority) to be taken by Tenant in order to Remediate and surrender the Premises (including any Alterations permitted by Landlord to remain in the Premises) at the expiration or earlier termination of the Term, free
    from any Contamination and acceptable for unrestricted use and occupancy (the &#8220;<b>Surrender Plan</b>&#8221;). Such Surrender Plan shall be accompanied by a current listing of (i) all Hazardous Materials licenses and permits held by or on behalf of any Tenant
    Party with respect to the Premises, and (ii) all Hazardous Materials used, stored, handled, treated, generated, Released, or disposed of from the Premises, and shall be subject to the review and approval of Landlord&#8217;s environmental consultant. In
    connection with the review and approval of the Surrender Plan, upon the request of Landlord, Tenant shall deliver to Landlord or its consultant such Haz Mat Documents as Landlord shall request. On or before Tenant&#8217;s surrender of the Premises, Tenant
    shall deliver to Landlord evidence that the approved Surrender Plan has been satisfactorily completed and Landlord shall have the right, subject to reimbursement at Tenant&#8217;s expense as set forth below, to cause Landlord&#8217;s environmental consultant to
    inspect the Premises and perform such additional testing and procedures as may be deemed reasonably necessary to confirm that the Premises are, as of the effective date of such surrender, free from any Contamination resulting from Tenant&#8217;s use and
    occupancy of the Premises. Tenant shall reimburse Landlord, as Rent, for the reasonable and actual expenses incurred by Landlord pursuant to this <u>Section 19</u>. Landlord shall have the unrestricted right to deliver such Surrender Plan and any
    report by Landlord&#8217;s environmental consultant with respect to the surrender of the Premises to third parties.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">If Tenant shall fail to prepare or submit a Surrender Plan approved by Landlord, or if Tenant shall fail to timely complete the approved Surrender
    Plan, or if such Surrender Plan, whether or not approved by Landlord, shall fail to adequately address any Contamination in, on or about the Premises, Landlord shall have the right to take such actions as Landlord may reasonably deem appropriate to
    assure that the Premises and the Project are surrendered free from any Contamination resulting from Tenant&#8217;s use and occupancy of the Premises, the cost of which actions shall be reimbursed by Tenant as Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">46</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>20.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Holding Over</u></b>.
    Tenant shall have the right (the &#8220;<b>Hold Over Right</b>&#8221;) to hold over possession of the Premises after the expiration (but not the earlier termination) of the Term for six&#160;(6) consecutive one (1)-month periods, upon the same terms and conditions set
    forth in this Lease (except that Tenant shall have no right to extend the Term pursuant to <u>Section 4</u> above), provided that such right shall automatically terminate as of the date Landlord delivers written notice (the &#8220;<b>New Lease Notice</b>&#8221;)
    to Tenant that Landlord has executed a Lease with a new tenant for the Premises or a portion thereof. If Landlord delivers a New Lease Notice, the Tenant&#8217;s tenancy pursuant to the Hold Over Right shall expire and terminate on the date that is thirty
    (30) days after delivery of the New Lease Notice, and all of Tenant&#8217;s surrender obligations as to the Premises must be completed by such date. Except pursuant to the Hold Over Right, if Tenant holds over after the expiration of the Term or after the
    effective date of termination based on the New Lease Notice, such tenancy shall be month-to-month only, and shall not constitute a renewal hereof or an extension for any further term, and in such case Base Rent shall be payable at a monthly rate equal
    to the product of (i) the Base Rent applicable during the last full month of the Term, and (ii)&#160;a percentage equal to one hundred fifty percent (150%). No hold over by Tenant or payment by Tenant after the expiration or early termination of this Lease
    shall be construed to extend the Term or prevent Landlord from immediate recovery of possession of the Premises by summary proceedings or otherwise. In addition, if Tenant holds over other than pursuant to the Hold Over Right, Tenant shall be
    responsible for all damages suffered by Landlord resulting from or occasioned by Tenant&#8217;s holding over, including consequential damages, and Tenant shall protect, defend, indemnify and hold Landlord harmless from all loss, reasonable and actual costs
    (including reasonable attorneys&#8217; fees) and liability resulting from such hold over, including, without limiting the generality of the foregoing, any claims made by any succeeding tenant founded upon such failure to surrender and any lost profits to
    Landlord resulting therefrom.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>21.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Notices</u></b>.
    Except as otherwise expressly provided in this Lease, all notices and demands which are required or may be permitted to be given to either party by the other hereunder shall be in writing and shall be sent by United States mail, postage prepaid,
    certified, or by personal delivery, or by a nationally-recognized overnight courier, addressed as set forth below, or to such other place as either party may from time to time designate in a notice to the other party given as provided herein. Notice
    shall be deemed given upon actual receipt (or attempted delivery if delivery is refused), if personally delivered, or one&#160;(1) business day following deposit for overnight delivery with a nationally-recognized overnight courier that provides a receipt,
    or on the third&#160;(3<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">rd</sup>) day following deposit in the United States mail in the manner described above. In no event shall either party use a post office box or other address
    which does not accept overnight delivery. Notwithstanding the foregoing, notices from Landlord regarding general Building operational matters may be sent via e-mail to the e-mail address(es) provided by Tenant to Landlord for such purpose.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">&#160;</td>
        <td style="text-align: justify; width: 1.5in">If to Landlord, to:</td>
        <td style="text-align: justify">Sudberry Development, Inc.</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">5465 Morehouse Drive, Suite 260</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">San Diego, CA 92121</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Attn: William E. Mayer, COO</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Email: [***]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">&#160;</td>
        <td style="text-align: justify; width: 1.5in">with a copy to:</td>
        <td style="text-align: justify">Michelle N. Cardinal, Esq.</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Email: [***]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">47</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">&#160;</td>
        <td style="text-align: justify; width: 1.5in">If to Tenant, to:</td>
        <td style="text-align: justify">Ionis Pharmaceuticals, Inc.</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">2855 Gazelle Ct.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Carlsbad, CA 92010</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Attn: General Counsel</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Email: [***]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-align: justify; text-indent: 0">with a copy (which shall not constitute notice) to:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Cooley LLP</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">4401 Eastgate Mall</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">San Diego, CA&#160;&#160; 92121-1909</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Attn: David L. Crawford, Esq.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 2in; text-align: justify; text-indent: 0">Email: [***]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.5in; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>22.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Parking Areas</u></b>.
    Tenant shall have an exclusive license to use the parking areas serving the Premises located on the Land throughout the Term of the Lease, and Tenant shall use such areas in compliance with applicable Laws. Landlord shall not be responsible for
    enforcing Tenant&#8217;s parking rights against any third parties; provided, however, Landlord shall not knowingly permit Landlord, its agents, contractors or employees, or other tenants or occupants of the Project to utilize such parking areas.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>23.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Brokers</u></b>.
    Landlord and Tenant each represents and warrants that it has not dealt with any broker, agent or other person (collectively, &#8220;<b>Broker</b>&#8221;) in connection with this transaction and that no Broker brought about this transaction, other than CBRE.
    Landlord and Tenant each hereby agree to indemnify and hold the other harmless from and against any claims by any Broker, other than CBRE, claiming a commission or other form of compensation by virtue of having dealt with Tenant or Landlord, as
    applicable, with regard to this leasing transaction. Landlord shall be responsible for all commissions due to CBRE arising out of the execution of this Lease in accordance with the terms of a separate written agreement between CBRE and Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>24.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Short Form Lease</u></b>.
    Landlord and Tenant may agree upon a short form of Lease or memorandum to be recorded in the land records.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>25.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Estoppel
        Certificates</u></b>. Tenant agrees at any time and from time to time upon no less than fifteen (15) business days&#8217; prior written notice by Landlord to execute, acknowledge, and deliver to Landlord a statement in writing certifying: (i) that this
    Lease is unmodified and in full force and effect (or if there have been modifications, that the same is in full force and effect as modified and stating the modifications), (ii) the date to which the Rent has been paid in advance, if any, (iii)&#160;stating
    whether or not to the best knowledge of the signer of such certificate Tenant or Landlord is in default in performance of any such covenant, agreement or condition contained in this Lease and, if so, specifying each such default of which the signer may
    have knowledge, and (iv) setting forth such further information with respect to the status of this Lease or the Premises as may be reasonably requested thereon, it being intended that any such statement delivered pursuant to this&#160;<u>Section 25</u>&#160;may
    be relied upon by any prospective purchaser of the Premises and any Mortgagee thereof and their respective successors and assigns. Landlord agrees at any time and from time to time upon not less than fifteen (15) business days&#8217; prior written notice by
    Tenant to execute, acknowledge and deliver to Tenant a statement in writing certifying (i) that this Lease is unmodified and in full force and effect (or if there shall have been modifications that the same is in full force and effect as modified and
    stating the modifications), (ii) the date to which the Rent has been paid in advance, if any, (iii) stating whether or not to the best knowledge of the signer of such certificate Tenant is in default in performance of any covenant, agreement or
    condition contained in this Lease, and, if so, specifying each such default of which the signer may have knowledge, and (iv) setting forth such further information with respect to the status of this Lease or the Premises as may be reasonably requested
    thereon, it being intended that any such statement delivered pursuant to this&#160;<u>Section 25</u>&#160;may be relied upon by any prospective assignee of Tenant&#8217;s interest in this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">48</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>26.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Governing Law,
        Jurisdiction, and Venue</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">26.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Governing Law</u>. This Lease shall be governed by
    and construed in accordance with the Laws of the State of California without giving effect to the principles of conflicts of law thereof or of any other jurisdiction that would result in the application of the Laws of any other jurisdiction.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">26.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Jurisdiction and Venue</u>. All actions and
    proceedings arising out of or relating to this Lease shall be heard and determined in any state or federal court located within San Diego County, California and the parties hereby irrevocably submit to the exclusive jurisdiction and venue of such
    courts in any such action or proceeding and irrevocably waive the defense of an inconvenient forum, improper venue, or lack of jurisdiction to the maintenance of any such action or proceeding. The consents to jurisdiction and venue set forth in this&#160;<u>Section







      26</u>&#160;shall not constitute general consents to service of process in the State of California and shall have no effect for any purpose except as provided in this&#160;<u>Section 26</u>&#160;and shall not be deemed to confer rights on any person or entity other
    than the parties. The parties agree that a final judgment in any such action or proceeding shall be conclusive and may be enforced in other jurisdictions by suit on the judgment or in any other manner provided by applicable Law;&#160;provided,&#160;however, that
    nothing in the foregoing shall restrict any party&#8217;s rights to seek any post-judgment relief regarding, or any appeal from, a trial court judgment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>27.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Attorneys&#8217; Fees</u></b>.
    If either party hereto fails to perform any of its obligations under this Lease or if any dispute arises between the parties hereto concerning the meaning or interpretation of any provision of this Lease, then the defaulting party or the party not
    prevailing in such dispute, as the case may be, shall pay any and all costs and expenses incurred by the other party on account of such default and/or in enforcing or establishing its rights hereunder, including, but not limited to, court costs, expert
    fees and costs and attorneys&#8217; fees and disbursements. In addition to other circumstances, a party shall be deemed to have prevailed in any such action if such action is dismissed upon the payment by the other party of the sums allegedly due or the
    performance of obligations allegedly not complied with, or if such party obtains substantially the relief sought by it in the action, irrespective of whether such action is prosecuted to judgment. The reasonable costs to which the prevailing party is
    entitled shall include costs of investigation, copying costs, electronic discovery costs, electronic research costs, telephone charges, mailing and delivery charges, information technology support charges, consultant and expert witness fees and costs,
    travel expenses, court reporter fees, transcripts of court proceedings not ordered by the court, mediator fees and attorneys&#8217; fees incurred in discovery and contempt proceedings. Tenant shall also pay all attorneys&#8217; fees and costs Landlord incurs in
    defending this Lease or otherwise protecting Landlord&#8217;s rights in any voluntary or involuntary bankruptcy case, assignment for the benefit of creditors, or other insolvency, liquidation or reorganization proceeding involving Tenant or this Lease,
    including all motions and proceedings related to relief from an automatic stay, lease assumption or rejection, use of cash collateral, claim objections, disclosure statements and plans of reorganization. The non-prevailing party shall also pay the
    attorneys&#8217; fees and costs incurred by the prevailing party in any post-judgment proceedings to collect and enforce the judgment. The covenant in the preceding sentence is separate and several and shall survive the merger of this provision into any
    judgment in connection with this Lease. Without limiting the generality of the foregoing, if Landlord utilizes the services of an attorney for the purpose of collecting any Rent due and unpaid beyond any applicable notice and cure period by Tenant or
    in connection with any other breach of this Lease by Tenant, Tenant shall pay Landlord&#8217;s actual attorneys&#8217; fees and expenses, regardless of the fact that no legal action may be commenced or filed by Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">49</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>28.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><font style="text-transform: uppercase"><u>Waiver Of Jury Trial</u></font></b>. TO THE EXTENT
    PERMITTED BY APPLICABLE LAW, EACH OF THE PARTIES HEREBY KNOWINGLY, INTENTIONALLY AND VOLUNTARILY IRREVOCABLY WAIVES ANY AND ALL RIGHTS TO TRIAL BY JURY IN ANY LEGAL ACTION ARISING OUT OF OR RELATED TO THIS LEASE.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>29.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Interpretation</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">29.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Broad Interpretation</u>. When a reference is made
    in this Lease to an Article, a Section, or Exhibit, such reference shall be to an Article of, a Section of, or an Exhibit to this Lease unless otherwise indicated. The Table of Contents and headings contained in this Lease are for reference purposes
    only and shall not affect in any way the meaning or interpretation of this Lease. Whenever the words &#8220;include,&#8221; &#8220;includes&#8221; or &#8220;including&#8221; are used in this Lease, they shall be deemed to be followed by the words &#8220;without limitation.&#8221; The words &#8220;hereof,&#8221;
    &#8220;herein&#8221; and &#8220;hereunder&#8221; and words of similar import when used in this Lease shall refer to this Lease as a whole and not to any particular provision of this Lease. The terms &#8220;or,&#8221; &#8220;any&#8221; and &#8220;either&#8221; are not exclusive. The word &#8220;extent&#8221; in the phrase
    &#8220;to the extent&#8221; shall mean the degree to which a subject or other thing extends, and such phrase shall not mean simply &#8220;if.&#8221; The word &#8220;will&#8221; shall be construed to have the same meaning and effect as the word &#8220;shall.&#8221; The definitions contained in this
    Lease are applicable to the singular as well as the plural forms of such terms and to the masculine as well as to the feminine and neuter genders of such terms. Any agreement or instrument defined or referred to herein means such agreement or
    instrument as from time to time amended, modified or supplemented, including by waiver or consent, and references to all attachments, schedules and exhibits thereto and instruments incorporated therein. References to a person are also to its permitted
    assigns and successors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">29.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Joint Drafting</u>. The parties have participated
    jointly in the negotiation and drafting of this Lease and, in the event an ambiguity or question of intent or interpretation arises, this Lease shall be construed as jointly-drafted by the parties and no presumption or burden of proof shall arise
    favoring or disfavoring the parties by virtue of the authorship of any provision of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">50</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>30.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Entire Agreement</u></b>.
    This Lease constitutes the entire agreement between the parties, and supersedes all other prior agreements and understandings, both written and oral, among the parties and their Affiliates, or any of them, with respect to the subject matter hereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>31.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Counterparts</u></b>.
    This Lease may be executed in one or more counterparts, each of which shall be deemed to be an original but all of which taken together shall constitute one and the same agreement and shall become effective when one or more counterparts have been
    signed by each of the parties and delivered to each of the other parties hereto. The parties hereto agree that this Lease may be electronically signed, and that any electronic signature appearing on this Lease is the same as a handwritten signature for
    the purposes of validity, enforceability and admissibility.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>32.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font></b></font><b><u>Indemnification</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">32.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Indemnification</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Subject to the waivers in&#160;<u>Section 9</u>, Tenant
    hereby indemnifies and agrees to defend, save and hold Landlord and the Landlord Parties harmless from and against any and all Third-Party Claims (defined below) for injury or death to persons or damage to property occurring within or about the
    Premises or the Project arising directly out of Tenant&#8217;s use or occupancy of the Premises or use of the Project (including, without limitation, any act, omission or neglect by Tenant or its agents, employees or contractors in or about the Premises or
    at the Project) or the breach or default by Tenant in the performance of any of its obligations hereunder. Such indemnity shall not apply to the extent caused by the gross negligence of the Landlord or any Landlord Parties; provided, however,
    Landlord&#8217;s liability for any such gross negligence or willful misconduct shall nevertheless be subject to <u>Section 32.4</u> below. The Landlord Parties shall not be liable for any damages arising from any act, omission or neglect of any tenant in
    the Project or Tenant Parties.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font> Subject to the waivers in&#160;<u>Section 9</u>, Landlord
    hereby indemnifies and agrees to defend, save and hold Tenant and Tenant&#8217;s agents, employees, directors and officers harmless from and against any and all Third-Party Claims arising out of or in connection with any damage or injury occurring in or on
    the Project (excluding the Premises) due to Landlord&#8217;s default or breach of its obligations pursuant to this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">32.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Procedures for Indemnification of Third-Party
      Claims</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Any Landlord Party or Tenant seeking indemnification
    under this Lease (an &#8220;<b>Indemnitee</b>&#8221;) with respect to any claim asserted against such Indemnitee by a person other than Landlord, Tenant or any Affiliate of Landlord or Tenant (a &#8220;<b>Third-Party Claim</b>&#8221;) in respect of any matter that is subject
    to indemnification hereunder shall promptly deliver to the other party (the &#8220;<b>Indemnifying Party</b>&#8221;) written notice (a &#8220;<b>Third-Party Claim Notice</b>&#8221;) setting forth a description in reasonable detail of the nature of the Third-Party Claim or, in
    the alternative, include a copy of all papers served with respect to such Third-Party Claim (if any); <i>provided</i>, <i>however</i>, that the failure to so transmit a Third-Party Claim Notice shall not affect the Indemnifying Party&#8217;s obligations
    under this&#160;<u>Section 32</u>, unless the Indemnifying Party is materially prejudiced as a result of such failure.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.2.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>If a Third-Party Claim is asserted against an
    Indemnitee, the Indemnifying Party shall be entitled to participate in the defense thereof and, if the Indemnifying Party delivers written notice to the Indemnitee within thirty (30) days after receipt of a Third-Party Claim Notice (or sooner, if the
    nature of the Third-Party Claim so requires) stating that the Indemnifying Party shall assume and control the defense of such Third-Party Claim and specifying any reservations to its defense (except that the failure to so specify any reservation to its
    defense in a timely-delivered written notice shall not affect the validity of such notice except to the extent the Indemnitee is materially prejudiced as a result of such failure), the Indemnifying Party may assume and control the defense thereof with
    counsel selected by the Indemnifying Party and reasonably satisfactory to the Indemnitee and settle such Third-Party Claim at the discretion of the Indemnifying Party;&#160;<i>provided</i>, that the Indemnifying Party shall not, except with the written
    consent of the Indemnitee (such consent not to be unreasonably withheld, conditioned or delayed), enter into any settlement or consent to entry of any judgment that: (i) does not include the provision by the person(s) asserting such claim to all
    indemnified parties of a full, unconditional and irrevocable release from all liability with respect to such Third-Party Claim, (ii) includes an admission of fault, culpability or failure to act by or on behalf of any Indemnitee, (iii) includes
    injunctive or other nonmonetary relief affecting any Indemnitee other than nonmonetary relief incidental to the monetary damages that does not restrict the operation of the businesses of the Indemnified Party or (iv) includes monetary amounts that
    would be payable by the Indemnified Party. If the Indemnifying Party elects to assume the defense of a Third-Party Claim, the Indemnifying Party shall not be liable to the Indemnitee for legal fees or expenses subsequently incurred by the Indemnitee in
    connection with the defense thereof;&#160;<i>provided</i>, that the Indemnitee shall have the right to participate in the defense thereof and to employ counsel, at its own expense, separate from the counsel employed by the Indemnifying Party (it being
    understood that the Indemnifying Party shall control such defense),&#160;<i>provided</i>,&#160;<i>further</i>, that if, based on the reasonable opinion of legal counsel to the Indemnitee, a conflict or potential conflict of interest exists between the
    Indemnifying Party and the Indemnitee which makes representation of both parties inappropriate under applicable standards of professional conduct, the reasonable fees and expenses of such separate counsel shall constitute indemnifiable liabilities
    pursuant to this <u>Section&#160;32</u>. The Indemnitee may retain or take over the control of the defense or settlement of any Third-Party Claim the defense of which the Indemnifying Party has elected to control if the Indemnitee irrevocably waives its
    right to indemnity under this&#160;<u>Section 32</u>&#160;and fully releases the Indemnifying Party with respect to such Third-Party Claim. If an Indemnifying Party elects not to assume and control the defense of any Third-Party Claim or fails to notify the
    Indemnitee of its election within thirty (30) days after receipt of a Third-Party Claim Notice, then such Indemnitee shall be entitled to continue to conduct and control the defense of such Third-Party Claim and the reasonable fees and expenses of
    counsel for the Indemnitee in connection with the defense of such Third-Party Claim shall constitute indemnifiable liabilities pursuant to this&#160;<u>Section 32</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.2.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>The parties shall reasonably cooperate with each other
    in the investigation, prosecution or defense of any Third-Party Claim. Such cooperation shall, upon reasonable written notice to the party providing such cooperation, include (i) providing, and causing their respective Affiliates to provide,
    documentary or other evidence in their possession or control that is reasonably related to the Third-Party Claim, (ii) implementing, and causing their respective Affiliates to implement, reasonable record retention or litigation hold policies and
    (iii)&#160;making available, and causing their respective Affiliates to make available, directors, officers and employees to give depositions or testimony. Except as otherwise provided in&#160;<u>Section 32.2.2</u> above, the party requesting such cooperation
    shall pay the reasonable out-of-pocket expenses incurred in providing such cooperation (including reasonable legal fees and disbursements) by the party (or Affiliate thereof, as the case may be) providing such cooperation and by its officers,
    directors, employees and agents, but not including reimbursing such party (or Affiliate thereof, as the case may be) or its officers, directors, employees and agents for their time spent in such cooperation.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">52</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">32.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Additional Matters</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>Indemnity payments or other payments in respect of any
    liabilities for which an Indemnitee is entitled to indemnification under this&#160;<u>Section 32</u>&#160;shall be paid reasonably promptly (but in any event within a reasonable amount of time after the final determination of the amount that the Indemnitee is
    entitled to indemnification under this <u>Section&#160;32</u>) by the Indemnifying Party to the Indemnitee as such liabilities are incurred upon demand by the Indemnitee, including reasonably satisfactory documentation setting forth the basis for the
    amount of such indemnity payments, including documentation with respect to calculations made and consideration of any insurance proceeds that actually reduce the amount of such liabilities.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font>If any Indemnitee has a claim against any Indemnifying
    Party under this <u>Section 32</u>&#160;that does not involve a Third-Party Claim being asserted or threatened against such Indemnitee (a &#8220;<b>Direct Claim</b>&#8221;), such Indemnitee shall promptly deliver to the Indemnifying Party a written notice (a &#8220;<b>Direct







      Claim Notice</b>&#8221;) setting forth a description in reasonable detail of the nature of the Direct Claim;&#160;<i>provided</i>, that the failure to so transmit a Direct Claim Notice shall not affect the Indemnifying Party&#8217;s obligations under this&#160;<u>Section
      32</u>, except to the extent that the Indemnifying Party is materially-prejudiced as a result of such failure.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">32.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Limitations on Liability</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.4.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font><b>EXCEPT AS EXPRESSLY SET FORTH IN <u>SECTIONS 6.5,
        17</u>, AND <u>20</u>, IN NO EVENT SHALL EITHER PARTY OR ANY OF ITS AFFILIATES BE LIABLE FOR INDIRECT, SPECIAL, EXEMPLARY, PUNITIVE OR CONSEQUENTIAL DAMAGES, INCLUDING PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES, LOSS OF PROFITS OR BUSINESS
      INTERRUPTION, HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE), BREACH OF STATUTORY DUTY OR OTHERWISE, IN CONNECTION WITH OR ARISING IN ANY WAY OUT OF THE TERMS OF THIS AGREEMENT OR
      THE PERFORMANCE HEREOF, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGES.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">53</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">32.4.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160; </font><b>NOTWITHSTANDING ANYTHING SET FORTH HEREIN AND
      EXCEPT IN THE EVENT OF FRAUD, MATERIAL MISREPRESENTATION, OR CRIMINAL ACTIVITY: (A) LANDLORD SHALL NOT BE LIABLE TO TENANT OR ANY OTHER PERSON FOR (AND TENANT AND EACH SUCH OTHER PERSON ASSUME ALL RISK OF) LOSS, DAMAGE OR INJURY, WHETHER ACTUAL OR
      CONSEQUENTIAL TO: TENANT&#8217;S PERSONAL PROPERTY OF EVERY KIND AND DESCRIPTION, INCLUDING, WITHOUT LIMITATION TRADE FIXTURES, EQUIPMENT, INVENTORY, SCIENTIFIC RESEARCH, SCIENTIFIC EXPERIMENTS, LABORATORY ANIMALS, WORK PRODUCT, LABORATORY WORK, SPECIMENS,
      SAMPLES, DATA, AND/OR SCIENTIFIC, BUSINESS, ACCOUNTING AND OTHER RECORDS OF EVERY KIND AND DESCRIPTION KEPT AT THE PREMISES AND ANY AND ALL INCOME DERIVED OR DERIVABLE THEREFROM; (B) THERE SHALL BE NO PERSONAL RECOURSE TO LANDLORD FOR ANY ACT OR
      OCCURRENCE IN, ON OR ABOUT THE PREMISES OR ARISING IN ANY WAY UNDER THIS LEASE OR ANY OTHER AGREEMENT BETWEEN LANDLORD AND TENANT WITH RESPECT TO THE SUBJECT MATTER HEREOF AND ANY LIABILITY OF LANDLORD HEREUNDER SHALL BE STRICTLY LIMITED SOLELY TO
      LANDLORD&#8217;S INTEREST IN THE PREMISES OR ANY PROCEEDS FROM SALE OR CONDEMNATION THEREOF, ANY INSURANCE PROCEEDS PAYABLE IN RESPECT OF LANDLORD&#8217;S INTEREST IN THE PREMISES OR IN CONNECTION WITH ANY SUCH LOSS AND BASE RENT COLLECTED BY LANDLORD FROM AND
      AFTER ANY JUDICIAL ADJUDICATION OF LIABILITY IN FAVOR OF TENANT AGAINST LANDLORD; AND (C) IN NO EVENT SHALL ANY PERSONAL LIABILITY BE ASSERTED AGAINST LANDLORD IN CONNECTION WITH THIS LEASE NOR SHALL ANY RECOURSE BE HAD TO ANY OTHER PROPERTY OR
      ASSETS OF LANDLORD OR ANY OF LANDLORD&#8217;S OFFICERS, DIRECTORS, EMPLOYEES, AGENTS OR CONTRACTORS. UNDER NO CIRCUMSTANCES SHALL LANDLORD OR ANY OF LANDLORD&#8217;S OFFICERS, DIRECTORS, EMPLOYEES, AGENTS OR CONTRACTORS BE LIABLE FOR INJURY TO TENANT&#8217;S BUSINESS
      OR FOR ANY LOSS OF INCOME OR PROFIT THEREFROM.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>33.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>CASp Inspection</u></b>.
    For purposes of Section 1938(a) of the California Civil Code, Landlord hereby discloses to Tenant, and Tenant hereby acknowledges, that the Premises have not undergone inspection by a Certified Access Specialist (CASp). In addition, the following
    notice is hereby provided pursuant to Section&#160;1938(e) of the California Civil Code:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#8220;A Certified Access Specialist (CASp) can inspect the subject premises and determine whether the subject premises comply with all of the applicable
    construction-related accessibility standards under state law. Although state law does not require a CASp inspection of the subject premises, the commercial property owner or lessor may not prohibit the lessee or tenant from obtaining a CASp inspection
    of the subject premises for the occupancy or potential occupancy of the lessee or tenant, if requested by the lessee or tenant. The parties shall mutually agree on the arrangements for the time and manner of the CASp inspection, the payment of the fee
    for the CASp inspection, and the cost of making any repairs necessary to correct violations of construction-related accessibility standards within the premises.&#8221;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">In furtherance of and in connection with such notice:&#160;(i)&#160;Tenant, having read such notice and understanding Tenant&#8217;s right to request and obtain a CASp inspection and
    with advice of counsel, hereby elects not to obtain such CASp inspection and waives its rights to obtain a CASp inspection with respect to the Premises to the extent permitted by any law now or hereafter in effect; and (ii)&#160;if the waiver set forth in
    clause&#160;(i) hereinabove is not enforceable pursuant to law, then Landlord and Tenant hereby agree as follows (which constitute the mutual agreement of the parties as to the matters described in the last sentence of the foregoing notice): (A)&#160;Tenant
    shall have the one-time right to request for and obtain a CASp inspection, which request must be made, if at all, in a written notice delivered by Tenant to Landlord on or before the date that is the earlier of (1)&#160;the date Tenant has commenced
    construction of its initial Tenant improvements, if any, or (2)&#160;the Commencement Date; (B)&#160;any CASp inspection timely requested by Tenant shall be conducted (1)&#160;between the hours of 9:00 a.m. and 5:00 p.m. on any business day, (2)&#160;only after ten (10)
    days&#8217; prior written notice to Landlord of the date of such CASp inspection, (3)&#160;in a professional manner by a CASp-designated by Landlord and without any testing that would damage the Premises in any way, and (4)&#160;at Tenant&#8217;s sole cost and expense,
    including, without limitation, Tenant&#8217;s payment of the fee for such CASp inspection, the fee for any reports prepared by a CASp in connection with such CASp inspection (collectively, the &#8220;<b>CASp Reports</b>&#8221;) and all other costs and expenses in
    connection therewith; (C)&#160;Tenant shall deliver a copy of any CASp Reports to Landlord within three&#160;(3) business days after Tenant&#8217;s receipt thereof; (D)&#160;Tenant, at its sole cost and expense, shall be responsible for making any improvements,
    Alterations, modifications and/or repairs to or within the Premises to correct violations of construction-related accessibility standards including, without limitation, any violations disclosed by such CASp inspection; and (E)&#160;if such CASp inspection
    identifies any improvements, Alterations, modifications and/or repairs necessary to correct violations of construction-related accessibility standards relating to those items of the Premises that are Landlord&#8217;s obligation to repair, if any, then
    (1)&#160;Landlord shall perform such improvements, Alterations, modifications and/or repairs as and to the extent required by law to correct such violations, and (2)&#160;notwithstanding anything to the contrary contained in this Lease, Tenant shall reimburse
    Landlord for the cost of such improvements, Alterations, modifications and/or repairs within thirty (30)&#160;days after Tenant&#8217;s receipt of an invoice therefor from Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>34.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Right of First
        Offer to Purchase</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">34.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Right of First Offer to Purchase</u>. During the
    Term of the Lease (including any extensions or renewals thereof), Tenant will have an ongoing right to purchase the Premises as set forth below (&#8220;<b>ROFO</b>&#8221;). The option set forth in this <u>Section 34</u> is personal to Ionis Pharmaceuticals, Inc.
    and may not be exercised by any other assignee or sublessee except in the event of a Permitted Transfer. If either (x)&#160;Landlord determines to sell the Premises to an unaffiliated buyer or (y)&#160;Landlord receives an unsolicited offer to sell the Premises
    to an unaffiliated potential buyer and Landlord wishes to either accept such offer or make a counter-offer to such potential buyer, Landlord shall notify Tenant of same, setting forth the essential terms of the sale (i.e., price, payment terms, &#8220;<b>AS
      IS</b>&#8221; or other condition of property, due diligence conditions, title and other contingencies, allocation of prorations and closing costs, and closing date) (&#8220;<b>ROFO Notice</b>&#8221;). Within ten (10) business days of receipt of Landlord&#8217;s ROFO Notice,
    Tenant may deliver to Landlord a notice of Tenant&#8217;s election to purchase the Premises, on the terms set forth in Landlord&#8217;s ROFO Notice, except that Tenant shall not have any due diligence contingency in recognition of Tenant&#8217;s use and occupancy of the
    Premises. Notwithstanding the foregoing, in no event shall any of the following permit Tenant to exercise its rights pursuant to this <u>Section 34</u>: (i)&#160;the sale of the Premises as part of a transaction involving more than one project owned by
    Landlord or its Affiliates and provided the sale includes one or more buildings comparable in size to the Premises, (ii) a merger or acquisition of Landlord into or by another entity, or (iii) the sale or transfer of any direct or indirect interest in
    Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">55</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">34.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Purchase Agreement</u>. If Tenant timely exercises
    any such right to purchase, the parties shall proceed diligently and in good faith and within sixty (60) days (as may be extended as set forth below, the &#8220;<b>ROFP Period</b>&#8221;) execute and deliver to one another an agreement of purchase and sale
    reasonably acceptable to Landlord and Tenant (the &#8220;<b>Purchase Agreement</b>&#8221;); provided, however, in the event the parties are proceeding diligently and in good faith to achieve the same, either party shall have the right to deliver written notice
    extending the ROFP Period for an additional thirty (30) days. The Purchase Agreement shall provide that Landlord agrees to sell and Tenant agrees to purchase the Premises &#8220;as-is, where-is,&#8221; with customary representations and warranties made by Landlord
    or its Affiliates, but excluding any representation or warranty, express or implied, of any kind by Landlord relating to the physical condition of the Premises. Each of the parties covenants to make a good faith effort to negotiate the Purchase
    Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">34.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord Right to Sell</u>. If (i) Tenant does not
    timely exercise such right, or (ii)&#160;Tenant timely exercises such right but Tenant does not execute the Purchase Agreement within the ROFP Period, and provided Landlord proceeded diligently and in good faith to achieve execution of the Purchase
    Agreement, or (iii) the parties timely execute the Purchase Agreement but the Purchase Agreement is thereafter terminated for any reason other than Landlord&#8217;s default, then Landlord shall thereafter be free to sell the Premises to any party and
    Tenant&#8217;s rights under this <u>Section 34</u>&#160;shall terminate and be of no further force or effect. Notwithstanding the foregoing, Landlord shall not sell the Premises for a price ninety-five percent (95%) or less of the price last-offered to Tenant
    nor on materially more-favorable terms regarding the closing date or amount of deposit(s) without first offering Tenant again the right to purchase the Premises on such more-favorable terms. Notwithstanding anything herein to the contrary, if Landlord
    fails to enter into an agreement with the proposed buyer within six (6) months following Tenant&#8217;s receipt of the ROFO Notice, the ROFO shall be reinstated and shall once again apply if Landlord determines to sell the Premises or receives an unsolicited
    offer as described in <u>Section 34.1</u> above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">34.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Exclusions</u>. Tenant&#8217;s rights under this&#160;<u>Section







      34</u>&#160;shall not apply to any transfer of the Premises to Landlord&#8217;s Mortgagee, either by foreclosure, trustee&#8217;s sale, deed in lieu of foreclosure, or any other transfer to any lender in the exercise of its rights, or the purchaser at any foreclosure
    sale if not the lender.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>35.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>OFAC</u></b>.&#160;
    Landlord and Tenant each hereby represent and warrant to the other, for the entirety of the Term, that it is currently (a) in compliance with and shall at all times during the Term of this Lease remain in compliance with the regulations of the Office
    of Foreign Assets Control (&#8220;<b>OFAC</b>&#8221;) of the U.S. Department of Treasury and any statute, executive order, or regulation relating thereto (collectively, the &#8220;<b>OFAC Rules</b>&#8221;), (b) not listed on, and shall not during the Term of this Lease be
    listed on, the Specially Designated Nationals and Blocked Persons List, Foreign Sanctions Evaders List, or the Sectoral Sanctions Identification List, which are all maintained by OFAC and/or on any other similar list maintained by OFAC or other
    Governmental Authority pursuant to any authorizing statute, executive order, or regulation, and (c) not a person or entity with whom a U.S. person is prohibited from conducting business under the OFAC Rules.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">56</font>&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>36.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Financial
        Information</u></b>.&#160; Within ten (10) business days after receipt of written request or any monetary Event of Default, Tenant shall execute and deliver to Landlord and/or its designee an audited financial statement or a current and complete
    financial statement for Tenant certified as true and correct by Tenant&#8217;s chief financial officer, but not more than once in any given twelve (12)-month period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>37.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Severability</u></b>.<b>&#160;
    </b>If any clause or provision of this Lease is illegal, invalid or unenforceable under present or future laws, then and in that event, it is the intention of the parties hereto that the remainder of this Lease shall not be affected thereby. It is also
    the intention of the parties to this Lease that in lieu of each clause or provision of this Lease that is illegal, invalid or unenforceable, there be added, as a part of this Lease, a clause or provision as similar in effect to such illegal, invalid or
    unenforceable clause or provision as shall be legal, valid and enforceable.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>38.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>EV Charging
        Stations</u></b>.&#160; Landlord shall not unreasonably withhold, delay or condition its consent to Tenant&#8217;s written request to install one or more electric vehicle car charging stations (&#8220;<b>EV Stations</b>&#8221;) in the parking areas serving the Premises;
    provided, however, that Tenant complies with all reasonable requirements, standards, Rules and regulations which may be imposed by Landlord, at the time Landlord&#8217;s consent is granted, in connection with Tenant&#8217;s installation, maintenance, repair and
    operation of such EV Stations, which may include, without limitation, Landlord&#8217;s designation of the location of Tenant&#8217;s EV Stations, and Tenant&#8217;s payment of all costs to the extent reasonable and actually incurred by Landlord or Tenant in connection
    with the installation, maintenance, repair and operation of each Tenant&#8217;s EV Station(s).&#160; Nothing contained in this paragraph is intended to increase the number of parking spaces which Tenant is otherwise entitled to use at the Premises pursuant to the
    Terms of this Lease nor impose any additional obligations on Landlord pursuant to this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>39.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Force Majeure</u>.&#160;
    </b>Landlord and Tenant shall not be responsible or liable for delays in the performance of its respective obligations hereunder, and no failure to perform such obligations as a result of such delays shall constitute a default hereunder, when caused
    by, related to, or arising out of acts of God, sinkholes or subsidence, strikes, lockouts, or other labor disputes, embargoes, quarantines, weather, national, regional, or local disasters, calamities, or catastrophes, inability to obtain labor or
    materials (or reasonable substitutes therefor) at reasonable costs to the extent not avoidable with advanced planning or inability to obtain utilities necessary for performance, governmental restrictions, orders, limitations, regulations, or controls,
    national emergencies, local, regional or national epidemic or pandemic, delay in issuance or revocation of permits, enemy or hostile governmental action, terrorism, insurrection, riots, civil disturbance or commotion, fire or other Casualty, and other
    causes or events that are beyond the reasonable control of the party obligated to perform (&#8220;<b>Force Majeure</b>&#8221;), except with respect to Landlord&#8217;s obligation to reimburse Tenant for costs as required pursuant to the Lease or Tenant&#8217;s obligations to
    pay Rent hereunder unless the national banks in the United States are closed as a result of Force Majeure in which case payment of Rent may be delayed until the national banks reopen for business. Any party claiming Force Majeure shall give the other
    party hereto written notice within five (5) days that the claiming party becomes aware of the delay caused by such Force Majeure event, explaining the nature or cause of the delay and stating the period of time the delay is expected to continue, if
    such delay can be reasonably determined. The claiming party shall use diligent, good-faith efforts to end the failure or delay and minimize the effects of such Force Majeure event. The claiming party shall resume the performance of its obligations as
    soon as reasonably practicable after the termination of the Force Majeure event.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>40.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Roof Equipment</u></b>.
    As long as Tenant is not in default under this Lease, Tenant shall have the exclusive right at its sole cost and expense, subject to compliance with all applicable Laws and all covenants, conditions and restrictions affecting the Land, to install,
    maintain, and remove on the top of the roof of the Building one or more satellite dishes, communication antennae, or other equipment (all of which having a diameter and height acceptable to Landlord) for the transmission or reception of communication
    of signals as Tenant may from time to time desire (collectively, the &#8220;<b>Roof Equipment</b>&#8221;) on the following terms and conditions:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requirements</u>. Tenant shall submit to Landlord
    (i) the plans and specifications for the installation of the Roof Equipment, (ii) copies of all required governmental and quasi-governmental permits, licenses, and authorizations that Tenant will and must obtain at its own expense, with the cooperation
    of Landlord, if necessary for the installation and operation of the Roof Equipment, and (iii) an insurance policy or certificate of insurance evidencing insurance coverage as required by this Lease and any other insurance as reasonably required by
    Landlord for the installation and operation of the Roof Equipment. Landlord shall not unreasonably withhold or delay its approval for the installation and operation of the Roof Equipment;&#160;<i>provided</i>,&#160;<i>however</i>, that Landlord may reasonably
    withhold its approval if the installation or operation of the Roof Equipment (A) may damage the Building Structure or the structural integrity of the Building, (B) may void, terminate, or invalidate any applicable roof warranty, or (C) is not properly
    screened from the viewing public.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Damage to Roof</u>. If installation of the Roof
    Equipment<b>&#160;</b>requires Tenant to make any roof cuts or perform any other roofing work, such cuts shall only be made in the manner designated in writing by Landlord; and any such installation work (including any roof cuts or other roofing work) shall
    be performed by Tenant, at Tenant&#8217;s sole cost and expense by a roofing contractor designated by Landlord. In the event Tenant requests Landlord&#8217;s approval for any roof cuts or to perform other roofing work, Landlord shall use commercially reasonable
    efforts to promptly respond with providing the designated manner for the cuts to be made and shall provide such response in no event later than ten (10) business days following receipt of the request. If Tenant or its agents shall otherwise cause any
    damage to the roof during the installation, operation, and removal of the Roof Equipment such damage shall be repaired promptly at Tenant&#8217;s expense and the roof shall be restored in the same condition it was in before the damage. Landlord shall not
    charge Tenant additional Rent for the installation and use of the Roof Equipment. If, however, Landlord&#8217;s insurance premium or tax assessment increases as a result of the Roof Equipment, Tenant shall pay such increase as Rent within thirty (30) days
    after receipt of a reasonably detailed invoice from Landlord. Tenant shall not be entitled to any abatement or reduction in the amount of Rent payable under this Lease if for any reason Tenant is unable to use the Roof Equipment. In no event whatsoever
    may the installation, operation, maintenance, or removal of the Roof Equipment by Tenant or its agents void, terminate, or invalidate any applicable roof warranty. Upon the occurrence of any such void, termination, or invalidation of any roof warranty
    due to any actions regarding Roof Equipment, Landlord may elect, at its option, to make Tenant responsible for the maintenance, repair, and replacement of the roof, notwithstanding Landlord&#8217;s obligations pursuant to <u>Section 8</u> above, or to claim
    an Event of Default hereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">58</font>&#160;</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Protection</u>. The installation, operation, and
    removal of the Roof Equipment shall be at Tenant&#8217;s sole risk. Tenant shall indemnify, defend, and hold Landlord harmless from and against any and all claims, costs, damages, liabilities and expenses (including, but not limited to, attorneys&#8217; fees) of
    every kind and description that may arise out of or be connected in any way with Tenant&#8217;s installation, operation, or removal of the Roof Equipment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Removal</u>. At the expiration or earlier
    termination of this Lease or the discontinuance of the use of the Roof Equipment by Tenant, Tenant shall, at its sole cost and expense, remove the Roof Equipment from the Building unless Landlord has instructed Tenant to allow the Roof Equipment to
    remain. If Tenant removes the Roof Equipment, Tenant shall leave the portion of the roof where the Roof Equipment was located in good order and repair, reasonable wear and tear excepted. If Tenant is obligated to but does not so remove the Roof
    Equipment, Tenant hereby authorizes Landlord to remove and dispose of the Roof Equipment and charge Tenant as Rent for all costs and expenses incurred by Landlord in such removal and disposal. Tenant agrees that Landlord shall not be liable for any
    Roof Equipment or related property disposed of or removed by Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Access</u>. Landlord grants to Tenant the right of
    ingress and egress on a twenty-four (24) hour, seven (7) day per week basis to install, operate, and maintain the Roof Equipment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Appearance</u>. If permissible by applicable Laws
    and reasonably practical, the Roof Equipment shall be painted the same color as the Building so as to render the Roof Equipment virtually invisible from ground level.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">40.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Assignment</u>. The right of Tenant to use and
    operate the Roof Equipment shall be personal to Ionis Pharmaceuticals, Inc. and, upon any permitted sublease of more than fifty percent (50%) of the Premises or assignment pursuant to a Permitted Transfer, to such sublessee or assignee. No other person
    or entity shall have any right to use or operate the Roof Equipment, and&#160;Tenant shall not assign, convey, or otherwise transfer to any person or entity any right, title, or interest in all or any portion of the Roof Equipment or the use and operation
    thereof except as set forth herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">59</font>&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    the same becomes available. Provided no Event of Default exists, Landlord shall notify Tenant in writing (the &#8220;<b>ROFO Lease Notice</b>&#8221;) before marketing the ROFO Space or entering into negotiations for the lease of the ROFO Space with any third
    party, or upon Landlord&#8217;s receipt of an offer to lease ROFO Space. Landlord&#8217;s notice must reflect the material terms upon which Landlord is willing to lease the ROFO Space, including without limitation, base rent, term, options to extend, rental
    abatement, and tenant improvement allowance. Tenant will have seven (7) business days after receipt of such notice to respond in writing as to whether or not Tenant elects to lease the ROFO Space upon the terms set forth in the ROFO Lease Notice,
    without modification or condition. If Tenant elects to lease the ROFO Space, then within thirty (30) days thereafter, Landlord shall prepare an amendment to this Lease and Tenant shall have the right to approve or provide proposed revisions. The
    parties shall thereafter proceed diligently and in good faith to execute a mutually agreeable amendment to this Lease to add the ROFO Space upon the terms and conditions set forth in the ROFO Lease Notice. Landlord will deliver the ROFO Space in the
    same condition as required of the original Premises under the Work Letter unless the parties agree otherwise in the amendment. If (i) Tenant elects not to lease, or (ii) Tenant does not exercise its Right of First Offer within the seven (7) business
    day time period specified above, or (iii) Tenant timely elects to lease the ROFO Space but the parties do not execute an amendment within thirty (30) days after Tenants&#8217; receipt of the proposed amendment, despite both parties proceeding diligently and
    in good faith to do so, then Landlord may lease the ROFO Space upon the same terms and conditions in the ROFO Lease Notice. In the event the Landlord elects to offer the ROFO Space upon economics that are materially better from what was offered to
    Tenant, Landlord must first offer the ROFO Space to Tenant upon such terms and conditions and in accordance with the requirements of this <u>Section&#160;41</u>. Once the ROFO Space or any portion thereof becomes available again, Tenant&#8217;s Right of First
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>42.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Approvals</u></b>.
    Each party hereto represents and warrants that it and the person executing this Lease on such party&#8217;s behalf has full authority and is duly authorized to enter into this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[Signatures on the following page]<br style="clear: both">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">IN WITNESS WHEREOF, the parties have executed this Lease as of the Effective Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
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        <td colspan="2"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">SUDBERRY DEVELOPMENT, INC.,</font></td>
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        <td colspan="2"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">a California corporation</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Its:</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>EXHIBIT A</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>[***]</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">Exhibit A<br>
  </p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; color: Red">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; text-align: center; margin-bottom: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-style: normal; font-variant: normal"><b>EXHIBIT &#8220;A&#8221;</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-variant: normal; color: black">THAT PORTION OF PARCEL </font><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1 <font style="font-weight: normal; font-variant: normal; color: black">OF CERTIFICATE OF COMPLIANCE NO. PLA-10-00002 RECORDED OCTOBER 24, 2011 AS DOC. NO. 2011-0557725, OF OFFICIAL
        RECORDS, SHOWN AS A REMAINDER OF EL CORAZON, ACCORDING TO MAP THEREOF NO. 16455 FILED IN THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY ON JUNE 9, 2021, BEING A PORTION OF LOT 7 OF RANCHO DEL ORO-MASTER SUBDIVISION WEST, ACCORDING TO MAP
        THEREOF NO. 11410 FILED IN THE OFFICE OF SAID COUNTY RECORDER DECEMBER 27, 1985, IN THE CITY OF OCEANSIDE, COUNTY OF SAN DIEGO, STATE OF CALIFORNIA, BEING MORE PARTICULARLY DESCRIBED AS FOLLOWS:</font></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; font-variant: normal">:ML M:\2425\09\Legal description\02 El
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font: normal 10pt Times New Roman, Times, Serif">WO 2425-0009 &#160;&#160;&#160;&#160;9/26/22</font></p>
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  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit A </p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-style: normal; font-variant: normal"><b>COMMENCING </b><font style="font-weight: normal">AT THE
        NORTHERLY TERMINUS OF THAT CERTAIN COURSE IN THE WESTERLY SIDELINE OF &#8220;AA" STREET AS SHOWN ON SAID MAP NO. 16455 AS N00&#176;31&#8217;10&#8221;E, 382.05 FEET; THENCE ALONG SAID WESTERLY SIDELINE SOUTH 00&#176;31&#8217;10&#8221; WEST, 382.05 FEET TO THE BEGINNING OF A 20.00 FOOT
        RADIUS CURVE CONCAVE NORTHWESTERLY; THENCE SOUTHWESTERLY THROUGH THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 64&#176;39&#8217;32&#8217;', A DISTANCE OF 22.57 FEET TO THE BEGINNING OF A 116.00 FOOT RADIUS CURVE CONCAVE EASTERLY, A RADIAL LINE TO SAID POINT
        BEARS NORTH 24&#176;49&#8217;18&#8221; WEST; THENCE SOUTHERLY THROUGH THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 80&#176;01'53&#8221;, A DISTANCE OF 162.03 FEET; THENCE LEAVING SAID WESTERLY SIDELINE RADIAL TO SAID CURVE SOUTH 75&#176;08&#8217;49&#8221; WEST, 14.50 FEET TO THE </font><b>TRUE







        POINT OF BEGINNING</b>, <font style="font-weight: normal">BEING THE BEGINNING OF A NON-TANGENT 130.50 FOOT RADIUS CURVE CONCAVE NORTHEASTERLY, A RADIAL LINE TO SAID POINT BEARS SOUTH 75&#176;08&#8217;49" WEST; THENCE SOUTHEASTERLY ALONG THE ARC OF SAID CURVE
        THROUGH A CENTRAL ANGLE OF 43&#176;27'44" A DISTANCE OF 98.99 FEET TO THE BEGINNING OF A 11.00 FOOT RADIUS REVERSE CURVE CONCAVE SOUTHWESTERLY, A RADIAL LINE TO SAID POINT BEARS NORTH 31<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">o</sup>41'05&#8221; EAST; THENCE SOUTHEASTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 58&#176;52'55" A DISTANCE OF 11.30 FEET; THENCE SOUTH 00&#176;34'00" WEST, 84.92 FEET; THENCE SOUTH 18&#176;26'00" WEST, 5.57 FEET TO THE BEGINNING OF A
        115.00 FOOT RADIUS CURVE CONCAVE NORTHWESTERLY; THENCE SOUTHWESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 25&#176;15'00" A DISTANCE OF 50.68 FEET; THENCE SOUTH 43&#176;41'00" WEST, 85.66 FEET; THENCE SOUTH 40&#176;17'00" WEST, 45.01 FEET; THENCE
        SOUTH 38<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">o</sup>39'00" WEST, 46.19 FEET TO THE BEGINNING OF A 18.00 FOOT RADIUS CURVE CONCAVE NORTHWESTERLY; THENCE SOUTHWESTERLY ALONG THE ARC OF SAID CURVE THROUGH A
        CENTRAL ANGLE OF 37&#176;37'00" A DISTANCE OF 11.82 FEET; THENCE SOUTH 76&#176;16'00" WEST, 17.00 FEET TO THE BEGINNING OF A 18.00 FOOT RADIUS CURVE CONCAVE NORTHERLY; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 38&#176;30'15" A
        DISTANCE OF 12.10 FEET TO THE BEGINNING OF A 280.00 FOOT RADIUS REVERSE CURVE CONCAVE SOUTHERLY, A RADIAL LINE TO SAID POINT BEARS NORTH 24&#176;46'15&#8217;' EAST; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 18&#176;59'15" A DISTANCE OF
        92.79 FEET; THENCE NORTH 84&#176;13'00" WEST, 6.48 FEET; THENCE SOUTH 15&#176;56'12" WEST, 31.30 FEET TO THE BEGINNING OF A NON-TANGENT</font></font> <font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">328.0&#160;&#160;&#160; <font style="font-weight: normal; font-variant: normal; color: black">FOOT RADIUS CURVE CONCAVE SOUTHERLY, A RADIAL LINE TO SAID POINT BEARS NORTH 15&#176;56'12" EAST; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 02&#176;27'58" A DISTANCE
        OF 14.12 FEET TO THE BEGINNING OF A NON-TANGENT 383.00 FOOT RADIUS CURVE CONCAVE SOUTHERLY, A RADIAL LINE TO SAID POINT BEARS NORTH 12&#176;02'14'' EAST; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 13&#176;03'58" A DISTANCE OF
        87.34 FEET TO THE BEGINNING OF A NON-TANGENT 327.50 FOOT RADIUS CURVE CONCAVE SOUTHERLY, A RADIAL LINE TO SAID POINT BEARS NORTH 01&#176;48'37" WEST; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 20&#176;40'35" A DISTANCE OF 118.19
        FEET TO THE BEGINNING OF A 432.50 FOOT RADIUS REVERSE CURVE CONCAVE NORTHERLY, A RADIAL LINE TO SAID POINT BEARS SOUTH 22&#176;29&#8217;12" EAST; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 03&#176;33'52" A DISTANCE OF 26.91 FEET; THENCE
        SOUTH 13&#176;00'46" EAST, 17.59 FEET TO THE BEGINNING OF A NON-TANGENT </font>450.0&#160;&#160;&#160; <font style="font-weight: normal; font-variant: normal; color: black">FOOT RADIUS CURVE CONCAVE NORTHERLY, A RADIAL LINE TO SAID POINT BEARS SOUTH 18&#176;41'30" EAST;
        THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 07&#176;17'25" A DISTANCE OF 57.26 FEET; THENCE SOUTH 78&#176;35'55" WEST, 322.29 FEET TO THE BEGINNING OF A 50.00 FOOT RADIUS CURVE CONCAVE NORTHERLY; THENCE WESTERLY ALONG THE ARC OF
        SAID CURVE THROUGH A CENTRAL ANGLE OF 09&#176;35'57" A DISTANCE OF 8.38 FEET; THENCE SOUTH 88&#176;11<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">,</sup>52" WEST, 100.54 FEET TO THE BEGINNING OF A 50.00 FOOT RADIUS CURVE CONCAVE
        SOUTHERLY; THENCE WESTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 09&#176;35'57" A DISTANCE OF 8.38 FEET; THENCE SOUTH 78&#176;35'55" WEST, 371.15 FEET TO THE BEGINNING OF A 50.00 FOOT RADIUS CURVE CONCAVE SOUTHEASTERLY; THENCE SOUTHWESTERLY
        ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 25&#176;46'30" A DISTANCE OF 22.49 FEET; THENCE SOUTH 52&#176;49'25" WEST, 152.61 FEET; THENCE NORTH 37&#176;10<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">,</sup>35<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">n </sup>WEST, 43.03 FEET; THENCE NORTH 45&#176;00'00" EAST, 11.14 FEET TO THE BEGINNING OF A 180.00 FOOT RADIUS CURVE CONCAVE NORTHWESTERLY; THENCE NORTHEASTERLY ALONG THE ARC OF
        SAID CURVE THROUGH A CENTRAL ANGLE OF 26&#176;05'00" A DISTANCE OF 81.94 FEET; THENCE NORTH 18&#176;55'00" EAST, 9.47 FEET; THENCE NORTH </font>1<font style="font-weight: normal; font-variant: normal; color: black">1 &#176;24'00" WEST, 64.00 FEET; THENCE NORTH
        19&#176;05'00" EAST, 179.00 FEET; THENCE NORTH 49&#176;20'00" EAST, 126.00 FEET; THENCE NORTH 58&#176;08'00" EAST, 251.00 FEET; THENCE NORTH 78&#176;37'00" EAST, 162.00 FEET; THENCE NORTH 85&#176;41'00" EAST, 48.00 FEET; THENCE NORTH 78&#176;37'00" EAST, 200.00 FEET; THENCE
        NORTH 71&#176;15'00" EAST, </font>47.0&#160;&#160;&#160; <font style="font-weight: normal; font-variant: normal; color: black">FEET; THENCE NORTH 78&#176;36'00" EAST, 220.00 FEET; THENCE SOUTH 11&#176;24&#8217;00" EAST, 2.00 FEET; THENCE NORTH 78&#176;36'00" EAST, 17.50 FEET TO THE
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        RADIUS CURVE CONCAVE SOUTHWESTERLY; THENCE SOUTHEASTERLY ALONG THE ARC OF SAID CURVE THROUGH A CENTRAL ANGLE OF 76&#176;34'49" A DISTANCE OF 46.78 FEET TO THE </font></font><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: normal; color: black"><b>TRUE POINT OF BEGINNING.</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; font-variant: normal">:ML M:\2425\09\Legal description\02 El
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font: normal 10pt Times New Roman, Times, Serif">WO 2425-0009 &#160;&#160;&#160;9/26/22</font></p>
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  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit A </p>
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        <td style="border-bottom: Black 1pt solid; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9/26/22</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0; text-indent: 0"><font style="font: normal 10pt Times New Roman, Times, Serif">WO 2425-0009 &#160;&#160;&#160;9/26/22</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>S<font style="font-family: Times New Roman, Times, Serif; font-variant: small-caps">ite</font> P<font style="font-family: Times New Roman, Times, Serif; font-variant: small-caps">lan</font></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>PROJECT</b></p>
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        <td>&#160;</td>
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        <td>&#160;</td>
        <td>&#160;</td>
        <td>&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
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    work of the major trades shall be competitively bid consistent with Landlord&#8217;s standard practice. Tenant shall have the ability to recommend subcontractors, and Landlord shall not unreasonably withhold, condition or delay its consent to requesting bids
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font> Promptly following the Effective Date, Tenant shall
    cause the Tenant Improvement Designer to prepare complete, detailed working plans and specifications (consistent with the Tenant TI Work Responsibilities) sufficient to enable subcontractors to bid on the work, to obtain the necessary building permits,
    and to then fully complete the TI Work, including without limitation, electrical requirements, telephone requirements, special HVAC requirements, plumbing requirements, and all interior and special finishes (once approved by Landlord, the &#8220;<b>TI Plans</b>&#8221;).







    The TI Plans must reflect all of the TI Work to be performed by or on behalf of Tenant. Any work not so included will not constitute part of Tenant&#8217;s Work and will require separate approval from Landlord as an Alteration. The TI Plans may be produced
    in phases reflecting the phases of construction. Tenant shall provide the first phase of the TI Plans in their then current state of completion to Landlord within ten (10) days after the Closing. Landlord shall, within ten (10) business days following
    its receipt of the TI Plans, either approve such TI Plans or provide Tenant with the reasons that Landlord is withholding such approval&#8212;which reasons must be reasonable. If Landlord does not approve the TI Plans, Tenant shall immediately meet with the
    Tenant Improvement Designer to have the TI Plans revised, in a manner acceptable to Tenant and consistent with Landlord&#8217;s comments, and then resubmitted to Landlord for approval (with such subsequent approvals/disapprovals being provided by Landlord
    within three (3) business days of the complete submittal of the revised TI Plans). Notwithstanding the foregoing, if Landlord fails to respond to any TI Plans within ten (10) business days of receipt thereof, and provided that such TI Plans included a
    cover notice that stated, in bold, capitalized letters, <b>FAILURE TO RESPOND WITHIN 10 BUSINESS DAYS WILL RESULT IN DEEMED CONSENT</b>, Landlord will be deemed to have approved the TI Plans.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Simultaneously with submission of the TI Plans to
    Landlord for approval, Tenant shall submit the TI Plans to the appropriate Governmental Authorities for issuance of applicable building permits necessary to allow the General Contractor to commence construction of the TI Work; provided, however, in no
    event shall Tenant submit the TI Plans for a second round of approval to the applicable Governmental Authorities prior to receipt and incorporation of any comments from Landlord, which must be provided by Landlord no later than the date Tenant receives
    comments from the applicable Governmental Authority. Once Landlord has approved the TI Plans, no changes, modifications, or alterations in the TI Plans or the TI Work may be made without the prior, written consent of Landlord, provided that Landlord
    may withhold its approval thereof based on the reasons for disapproval set forth in <u>Section 4.2</u> below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Tenant&#8217;s Work shall be completed by Tenant
    through the General Contractor in a first-class and workmanlike manner in accordance with the Landlord-approved TI Plans, this Work Letter, and in compliance with all applicable laws, codes, ordinances, and other governmental requirements then
    applicable to the Premises and the Building. Except to the extent Landlord and Tenant agree otherwise (e.g. for specialized trades where competitive bids are not practical), subcontracting work of the major trades shall be competitively bid by at least
    three subcontractors. Tenant and Landlord shall each have the ability to recommend subcontractors, and Tenant shall request bids from such recommended subcontractors. The cost of the TI Work, including both hard and soft costs, will be Tenant&#8217;s sole
    responsibility, subject to application of the TI Work Allowance (as defined below), as provided below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Commencing on the date that Landlord commences
    Landlord&#8217;s Work and subject to approval by the City of Oceanside, Landlord shall allow Tenant access to the applicable portion of the Premises for the sole purpose of Tenant performing the Tenant&#8217;s Work in the applicable portion of the Premises and
    without the obligation to pay Rent until the Rent Commencement Date. &#160;Landlord and Tenant shall cooperate and Tenant will proceed in good faith to avoid causing any delays or disruptions. Tenant further acknowledges and agrees that except as caused by
    the gross negligence or willful misconduct of Landlord, Landlord shall not be liable for any injury, loss or damage which may occur to any of Tenant&#8217;s Work made in or about the Premises in connection with such entry or to any property placed therein
    prior to the Lease Commencement Date, the same being at Tenant&#8217;s sole risk and liability. &#160;Tenant shall be liable to Landlord for any damage to any portion of the Premises, including the TI Work, caused by Tenant or any of Tenant&#8217;s employees, agents,
    contractors, subcontractors, consultants, workmen, mechanics, suppliers and invitees.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant acknowledges and agrees that, at Tenant&#8217;s
    request, Landlord took certain actions and incurred certain costs prior to the Effective Date in connection with the TI Work, including without limitation, the preparation of those design documents, site plan and elevations by SCA Architecture in an
    amount not exceeding $300,000 (the &#8220;<b>Early Start Action Costs</b>&#8221;). While the Early Start Action Costs have been included as part of the Allowable Costs (as defined below), in the event of any early termination of the Lease which is not as a result
    of Landlord&#8217;s actions (including but not limited to Landlord&#8217;s failure to timely deliver the Premises pursuant to <u>Section 2</u> of the Lease), Tenant shall reimburse Landlord for fifty percent (50%) of the Early Start Action Costs within ten (10)
    days of Tenant&#8217;s receipt of Landlord&#8217;s written statement (including invoices, as applicable) of the Early Start Action Costs. Such obligation shall survive such early termination of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall pay Landlord a construction management
    fee in connection with the TI Work in the amount of $12,000 per month, beginning upon the commencement of construction of Landlord&#8217;s Work and continuing to be due on the first day of each month thereafter until the earlier of (1) expiration of
    twenty-four (24) months, or (2) termination of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">3.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall enter into the TI Work Contract (as
    defined below) as and when required by <u>Section&#160;7.1.2</u>, below, unless Landlord approves otherwise in writing. The satisfaction of such obligation is and shall be a condition precedent to Landlord&#8217;s obligation to commence the Landlord&#8217;s Work, and
    any failure thereof shall constitute a Tenant Delay unless otherwise approved in writing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>4.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Modifications to
        Landlord&#8217;s Work</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">4.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant may request changes in the Landlord&#8217;s Work
    following approval of the TI Plans or during construction, only by written request from Tenant&#8217;s Representative to Landlord&#8217;s Representative on a form reasonably approved by Landlord. All such changes shall be subject to Landlord&#8217;s prior written
    approval in accordance with this <u>Section&#160;4</u>. Landlord may also propose, subject to Tenant&#8217;s approval as set forth below, changes to the Landlord&#8217;s Work following approval of the Approved Plans if required by any Governmental Authority or
    required by changing circumstances or events beyond Landlord&#8217;s reasonable control. Prior to commencing any changes, Landlord shall prepare and deliver to Tenant, for Tenant&#8217;s approval, a change order (the &#8220;<b>Change Order</b>&#8221;) setting forth the reason
    for the change, the estimated additional time required to perform the change and the total cost of such change, which will include associated architectural, engineering, and construction contractor&#8217;s fees, delay costs (including Rent which would be
    payable, but for such delay) and additional coordination costs. If Tenant fails to approve a Change Order requested by Tenant within three (3) business days after delivery thereof by Landlord, Tenant shall be deemed to have withdrawn the proposed
    Change Order and Landlord shall not proceed to perform the subject change. If Tenant fails to approve or reject any Change Order proposed by Landlord within three (3) business days after delivery thereof by Landlord, Landlord shall not proceed to
    perform the subject change, and Landlord shall have the right to modify and re-submit such Change Order for Tenant&#8217;s review. Upon Landlord&#8217;s receipt of Tenant&#8217;s approval of a Change Order, the General Contractor shall proceed to perform the change,
    with any Landlord&#8217;s Work Excess Cost (as defined below) to be paid as set forth in <u>Section 5</u> below, and any TI Work Excess Amount (as defined below) to be paid as set forth in <u>Section 6</u> below. All construction and completion dates for
    Landlord&#8217;s Work which are affected by the Change Order, including without limitation, the Estimated Commencement Date, shall be revised accordingly, and in no event shall such changes be considered a Tenant Delay. The cost of preparing any
    Tenant-requested Change Order, whether or not such change is ultimately approved, will be deducted from the TI Work Allowance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">4.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord may, among other reasons, withhold its
    approval of any Tenant-requested revision or change pursuant to <u>Section 4.1</u> above, if such revision or change would require work which: (i) exceeds or affects the structural integrity of the Building or systems serving the Project; (ii) is not
    approved (if such approval is required) by the holder of any deed of trust encumbering the Premises at the time the work is proposed or is to be undertaken, despite Landlord&#8217;s commercially-reasonable efforts to obtain such approval; (iii) violates any
    agreement which affects the Premises or which binds Landlord; (iv)&#160;Landlord reasonably believes will materially increase the cost of operation or maintenance of the Building or the Project unless Landlord provides Tenant with an estimate of such
    increase and Tenant agrees to be responsible for such additional costs; (v) Landlord reasonably believes will materially reduce the market value of the Building or the Project; (vi) does not conform to applicable building codes or is not approved by
    any Governmental Authority with jurisdiction over the Premises and/or the Building; (vii) does not conform to Landlord&#8217;s Project-standard Tenant finish (as modified by the approved TI Plans) or improvement specifications; or (viii) Landlord reasonably
    believes will result in more than a five (5)-business day delay in the completion of Landlord&#8217;s Work, or result in a material increase in the cost of Landlord&#8217;s Work unless Landlord provides Tenant with an estimate of such increase and Tenant agrees to
    reimburse Landlord for such additional costs or unless Tenant agrees for the TI Work Allowance to be applied to such increase.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif">5.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></font><u>[Intentionally
      Omitted]</u>.</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>6.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>TI Work Allowance</u></b>.
    Tenant shall be responsible for bearing all costs and expenses of completing the TI Work and the Tenant&#8217;s Work, except that Landlord will provide Tenant with a tenant improvement allowance (to be applied only against the cost of the TI Work) up to a
    maximum amount of $150.00 per rentable square foot of the Premises (the &#8220;<b>TI Work Allowance</b>&#8221;). Additionally, if Landlord does not use all of the contingency allocated for Landlord&#8217;s Work upon Substantial Completion thereof, any such unused amount
    shall be added to the TI Work Allowance. All costs and expenses of the TI Work in excess of the TI Work Allowance shall be Tenant&#8217;s sole responsibility and expense and shall be payable in accordance with the provisions of this <u>Section 6</u>. The TI
    Work Allowance may be referred to as an &#8220;<b>Allowance</b>&#8221;. Upon the occurrence of an Event of Default under the Lease, Landlord shall have the right, notwithstanding anything to the contrary in the Lease or this Work Letter, to withhold payment of all
    or any portion of an Allowance. In connection with the foregoing, Landlord may, in its discretion, suspend or cease all other obligations of Landlord under the terms of this Work Letter until such time as such Event of Default is cured, without
    affecting any other rights or remedies of Landlord in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord and Tenant acknowledge that the cost of the
    TI Work is likely to exceed the amount of the TI Work Allowance (any such excess, the &#8220;<b>TI Work Excess Amount</b>&#8221;). Following commencement of Landlord&#8217;s Work, Landlord may notify Tenant that, within five (5) business days of receipt of Landlord's
    written notice, Tenant shall deposit an amount not to exceed the equivalent of the TI Work Allowance (the &#8220;<b>Secured Portion</b>&#8221;) in an escrow or other account, or provide such other evidence of funds (such as, but not limited to, segregated escrow
    accounts), or provide security for the payment (such as, but not limited to, a bond, letter of credit) of the Secured Portion, or otherwise secure in a manner reasonably acceptable to Landlord and its lender, the Secured Portion for application toward
    the costs of the TI Work. For purposes of clarification, the parties acknowledge that only the costs of the TI Work shall be used to determine any TI Work Excess Amount, and no other costs of Tenant&#8217;s Work, including without limitation, the costs of
    any Tenant&#8217;s business personal property, furniture, furnishings, trade or business fixtures, cabling, and equipment, shall be included in the calculation of determining the TI Work Excess Amount at any time. Any failure by Tenant to pay, deposit funds,
    or provide security as may be required, within five (5) business days following receipt of Landlord's written notice: (i) will constitute a default under this Lease, and (ii) may, in addition, be treated by Landlord as: (a) a Tenant Delay excusing
    Landlord from commencing/continuing with the Landlord's Work (until Tenant pays such amount), or (b) Tenant's irrevocable deemed election to pay the Secured Portion by increasing the Base Rent under this Lease by an amount sufficient to fully amortize
    the Secured Portion over the Term plus interest at 15 percent per annum (notwithstanding any contrary written election by Tenant). Upon completion of the TI Work in accordance with this Lease, Landlord shall credit any unused Secured Portion against
    Rent next coming due under this Lease. In the event this Lease is terminated and except to the extent such termination is due to an Event of Default by Tenant, within ten (10) business days following such termination, any unused Secured Portion shall
    be immediately released.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>If Landlord elects to treat Tenant's failure to
    timely pay the Secured Portion as a deemed election to amortize the Secured Portion through an increase to Base Rent (pursuant to clause (b) of <u>Section 6.1</u>, above), this Lease will be automatically amended to reflect such increase and the
    Landlord shall provide Tenant with a written memorandum memorializing such amendment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The TI Work Allowance may be applied by Tenant only
    against all reasonable hard costs incurred by Tenant in connection with the design, permitting, constructing and completion of the TI Work, such as labor, material, and other similar construction costs, the Tenant&#8217;s Contractor&#8217;s Fee (as defined below)
    and general conditions relating to the TI Work, and costs of all inspections and engineering services. The cost of TI Work does not include, and the TI Work Allowance will not be applied towards, the cost of Tenant&#8217;s furniture, fixtures, and/or
    equipment, or other items of personal property, all of which will be treated as a part of Tenant&#8217;s Work and will be Tenant&#8217;s sole responsibility and expense. The TI Work Allowance also may not be applied towards (i) the cost of any of the Tenant&#8217;s Work
    other than the TI Work, (ii) Tenant&#8217;s exterior signage costs, or (iii) any payments to Tenant or its affiliates; or (iv) soft costs such as costs of space planning, architectural work, costs of the preparation of the TI Plans, permits, blueprints, and
    reimbursables, all of which items will be Tenant&#8217;s sole responsibility and expense. In addition, none of the TI Work Allowance may be applied toward construction management costs.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">6.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Subject to <u>Section 5</u> above and the provisions
    of <u>Section 6</u>, the TI Work Allowance shall be funded to Tenant or at Tenant&#8217;s election, the person ultimately entitled to receive such funds, upon Tenant&#8217;s submittal to Landlord of a monthly Request for Payment subject to the requirements set
    forth in this Work Letter. Landlord shall pay invoices within thirty-five (35) days of receipt of a complete submission from Tenant (as set forth below), directly to the applicable vendor as requested by Tenant or to Tenant (to the extent Tenant has
    paid such requisitioned costs) on a progress payment basis, subject to the pari passu process above and approval and conditions imposed by Landlord&#8217;s lender. With respect to any portion of the TI Work Allowance that is disbursed by Landlord to pay for
    applicable costs that were incurred by Tenant (such as costs for the architect and other costs directly incurred by Tenant), as a condition to Landlord&#8217;s disbursement of any portion of the TI Work Allowance for such costs, Tenant shall provide Landlord
    with (A) appropriate paid or unpaid receipts or invoices for the amount requested to be paid from the TI Work Allowance, (B) partial lien waivers for such work from all persons or entities that could file mechanics&#8217; or materialmen&#8217;s liens against the
    Building or the Project with respect to all work performed or services or materials provided through the date of each such invoice (subject only to receipt of the requisitioned amount) and final lien waivers for final payments, as applicable, for any
    contracts greater than Twenty-Five Thousand and No/100 Dollars ($25,000.00), (C) written authorization from Tenant to disburse the portion of the TI Work Allowance being requisitioned, and (D) such other documentation as may be reasonably requested by
    Landlord or its lender<b><i>.</i></b> Tenant may not make a requisition for application of the TI Work Allowance more frequently than once a month. Tenant shall deliver each requisition (and accompanying documentation as required herein) to Landlord no
    later than the 25<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> of each month. The final Request for Payment and release of any retainage shall be accompanied by paid invoices in at least the amount of the TI Work
    Allowance, and Tenant&#8217;s full satisfaction of each of the following requirements:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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    <div style="TEXT-ALIGN: center">&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant must have completed the TI Work in
    accordance with the Landlord-approved TI Plans and have commenced the payment of Rent following the Rent Commencement Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>A Notice of Completion must have been properly
    recorded for the TI Work and thirty-five (35) days have elapsed since the date of such recording with no mechanics&#8217; or materialmen&#8217;s liens having been filed (or such filed liens shall have been released).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant has submitted a complete set of &#8220;as built&#8221;
    plans and specifications to Landlord reflecting all of the TI Work and generally conforming to the TI Plans.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant has provided to Landlord copies of all
    insurance certificates required under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>A temporary certificate of occupancy or its
    equivalent for the Premises has been issued by the appropriate governmental agency.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant has provided Landlord with all material and
    labor lien releases from Tenant&#8217;s Contractor and all first-tier material suppliers and subcontractors involved in the TI Work contingent upon payment only. Once the final Request for Payment has been disbursed, Tenant can provide final unconditional
    lien releases.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant has provided Landlord with copies of all
    construction warranties and guarantees in connection with construction of Tenant&#8217;s Work along with a written assignment satisfactory to Landlord of all such warranty and guaranty rights under the contract with the Tenant&#8217;s Contractor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.8<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord has inspected and approved the TI Work and
    is satisfied that the TI Work has been performed in a good and workmanlike manner in accordance with the approved TI Plans; provided, however, no such inspection shall impose any liability upon Landlord, nor absolve Tenant or the Tenant&#8217;s Contractor
    from liability for any defect or failure to comply with the requirements hereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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    <div style="TEXT-ALIGN: center">&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">6.4.9<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant has provided Landlord with such information
    as Landlord or its lender may reasonably request.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>7.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Allowable Costs;
        Determination of Base Rent</u></b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Total Project Cost Estimate</u>. The parties
    hereby acknowledge and agree that Base Rent is intended to be determined based on a 7.9% return on Landlord&#8217;s costs and expenses to acquire, design, develop and construct the Building shell and core and related areas of the Premises for Tenant&#8217;s
    Permitted Use. In connection therewith, prior hereto, Landlord provided to Tenant, and Tenant approved, that certain itemized estimate of the Allowable Costs, which estimate is attached hereto as <u>Schedule 3</u> (the &#8220;<b>Cost Estimate</b>&#8221;). The
    Cost Estimate is subject to adjustment for costs attributable to approved Change Orders and Tenant Delays as well as to update the Cost Estimate based on the Construction Contracts, to the extent applicable.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">7.1.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Allowable Costs</b>&#8221; means actual costs
    incurred by Landlord for the design and construction of the Landlord&#8217;s Work, including without limitation, design fees or costs (including both engineering and architectural/planning fees and costs, blueprints, and reimbursables and also including such
    fees and costs as Landlord incurred prior to the Effective Date at Tenant&#8217;s request), and all third-party labor (i.e. excluding employees of Landlord or an Affiliate of Landlord), materials, and construction costs; supervision/construction management
    fees; the general contractor&#8217;s fee and general conditions; costs of all inspections, all applicable taxes, permit fees and development impact fees required by the City of Oceanside or other governmental agencies with jurisdiction over the construction
    of the Landlord&#8217;s Work; the cost of utilities as necessary and reasonable to construct and install the Landlord&#8217;s Work; financing, real estate taxes, professional fees (including without limitation legal and brokerage), and other soft costs incurred in
    connection with Landlord&#8217;s Work and all other fees and expenses contemplated by the Lease or this Work Letter incurred by Landlord in connection with the design and construction of Landlord&#8217;s Work and the TI Work. The Allowable Costs shall also
    include: (w) the amount of the TI Work Allowance and costs associated therewith, (x) a development fee in the amount of 5.0% of the hard-shell construction costs set forth in the Cost Estimate, (y) a construction management fee in the amount of 1.0% of
    such hard-shell construction costs, and (z) the value of the Land as set forth in the Cost Estimate. Notwithstanding the foregoing, Allowable Costs will not include the following: (i) any entertainment costs, and costs of transportation, meals and
    lodging not directly related to the construction of the Landlord&#8217;s Work; (ii) the costs, including fines, penalties, and legal fees or costs, of curing violations of applicable building codes or other applicable laws (it being agreed, however, that
    compliance with directives from field or plan inspectors will not be treated as costs to cure violations); (iii) any amounts paid to subsidiaries or Affiliates of Landlord for any services or supplies or other materials to the extent amounts incurred
    are in excess of those which would have been incurred if such supplies or services were obtained from unrelated third parties; (iv) intentionally omitted; (v) any Allowable Costs to the extent Landlord receives reimbursement from Tenant, any insurance
    companies or other third parties; (vi) amounts represented by any claims, defenses, credits or offsets that Landlord actually receives under the Construction Contract (defined below) or other contracts for goods and/or services that would otherwise
    qualify as Allowable Costs; or (vii) costs incurred as a result of any Landlord Delays.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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    <div style="TEXT-ALIGN: center">&#160;</div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">7.1.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Construction Contract</u>. Landlord shall enter
    into a construction contract with the General Contractor for the construction of the Building (the &#8220;<b>Building Work Contract</b>&#8221;), and Tenant shall enter into a construction contract with the General Contractor for the TI Work (the &#8220;<b>TI Work
      Contract</b>&#8221;), each of which shall be subject to approval by the other party hereto, which approval shall not be unreasonably withheld, conditioned or delayed, and approval of its Mortgagee, if required. Each of the Building Work Contract and the TI
    Work Contract (each, a &#8220;<b>Construction Contract</b>&#8221; and collectively, the &#8220;<b>Construction Contracts</b>&#8221;) will be on a &#8220;cost plus, with a guaranteed maximum price&#8221; basis. Each Construction Contract will provide: (i) that retainage on all payments
    (except for General Conditions Costs (as defined below)) shall be no less than 10% (or the amount required by law) until 50% of the work covered by such Construction Contract (as the case may be, the &#8220;<b>Contract Work</b>&#8221;) is completed, after which
    the retainage shall be no less than 5% (or the amount required by law), but in no case shall the retainage ever be less than 5% of the contract price or the amount of retainage required by law (the &#8220;<b>Retainage</b>&#8221;) until the Contract Work is
    completed to Landlord&#8217;s and Tenant&#8217;s reasonable satisfaction in accordance with this Lease, with releases of Retainage attributable to any particular subcontract subject to: (A)&#160;satisfactory completion of all work required under such subcontract, and
    (B) receipt of lien waivers reasonably acceptable to Landlord and Tenant; (ii) that Tenant and Landlord must approve any changes to the Building Plans and the Approved Plans as required by and in accordance with this Lease; (iii) that General
    Contractor shall provide a credit associated with any deductive change order (which will include a corresponding decrease in Contractor&#8217;s Fee; (iv)&#160;that General Contractor shall work with Landlord and Tenant to assess the various options available to
    reduce costs throughout the completion of the Contract Work; (v) that General Contractor shall, to the extent permitted by law, indemnify, defend and hold Landlord, the Landlord Parties, Tenant and the Tenant Parties harmless from and against any and
    all losses, liabilities, damages, costs and expenses (including reasonable attorneys&#8217; fees) resulting from actual or threatened claims by third parties arising in connection with the completion of the Landlord&#8217;s Work, the TI Work, and General
    Contractor&#8217;s activities on or about the Premises, except to the extent caused by the party to be indemnified; (vi)&#160;that the total amount of General Contractor&#8217;s compensation for its overhead and profit, and for expenses that are not a direct cost of
    the Contract Work, shall not exceed five percent (5%) of the total amount of the Construction Contract (&#8220;<b>Contractor&#8217;s Fee</b>&#8221;), and any change orders that affect the Cost Estimate, including additions and reductions, will result in proportionate
    changes to the Contractor&#8217;s Fee, both upward and downward, calculated on the same stipulated percentage; (vii)&#160;that any subcontractor or supplier fee as compensation for its overhead and profit, and for expenses that are not a direct cost of the
    Contract Work (&#8220;<b>Subcontractor&#8217;s Fee</b>&#8221;) for a change order requested by Tenant, shall not exceed fifteen percent (15%) of such increased cost; (viii) that General Contractor shall provide Landlord and Tenant with a detailed itemization of the
    types, categories and amounts of costs to be included in General Contractor&#8217;s general conditions costs, which shall be a stipulated amount or rate (the &#8220;<b>General Conditions Costs</b>&#8221;); (ix) intentionally omitted; (x) that, at Tenant&#8217;s option,
    General Contractor will require each first (1st) tier subcontractor to provide lien waivers in a form and substance reasonably acceptable to Landlord, as to the construction of the Building, and Tenant, as to the TI Work, as a condition to such
    subcontractor&#8217;s right to receive its final payment relating to such Contract Work, as the case may be; (xi) that Tenant is an intended third-party beneficiary of the Building Work Contract, and Landlord is an intended third-party beneficiary of the TI
    Work Contract; (xii) that any work for construction of the Building performed on a cost-plus basis shall be subject to the requirement that any and all costs and expenses, including insurance premiums, shall be commercially-reasonable and substantiated
    with detailed documentation to be provided to Landlord and Tenant upon request; and (xiii) will secure Landlord&#8217;s and Tenant&#8217;s rights to audit all costs under the Construction Contracts. Promptly upon request and in any event within ninety (90) days
    after the Effective Date, Landlord shall provide Tenant with a copy of the executed Building Work Contract, together with all schedules, exhibits, and any amendments, and Tenant shall provide Landlord with a copy of the executed TI Work Contract,
    together with all schedules, exhibits, and any amendments. Until each Construction Contract has been executed, each party shall, upon request by the other party hereto, provide the requesting party with a copy of the latest draft of its respective
    Construction Contract. Subject to <u>Section 4</u> above, Landlord shall not amend or modify the Building Work Contract without Tenant&#8217;s prior written consent if the amendment or modification would (w) make the Construction Contract&#8217;s provisions
    inconsistent with the requirements set forth above in this <u>Section 7</u>, (x) adversely affect any potential savings on the Cost Estimate, or (y) delay the Lease Commencement Date. Tenant may withhold its consent to any such amendment or
    modification in Tenant&#8217;s reasonable discretion.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">7.1.2.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160; </font>Landlord hereby assigns to Tenant all warranties and
    guaranties by the General Contractor or any subcontractor relating to the TI Work or any other portion of the Landlord Work to be maintained by Tenant pursuant to the Lease. In the event of any TI Work or approved Alterations modifying any Building
    Systems, Landlord shall use commercially-reasonable efforts to obtain assurances from the applicable issuing parties that applicable warranties as to the affected Building Systems will not be voided by such modifications, provided such work is
    performed by Landlord&#8217;s contractors and in compliance with reasonable conditions associated therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 2in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Actual Cost</u>. Within sixty (60) days after
    Substantial Completion of Landlord&#8217;s Work, Landlord will determine the final actual Allowable Costs (&#8220;<b>Actual Cost</b>&#8221; or &#8220;<b>Actual Costs</b>&#8221;). Landlord will provide written notice to Tenant of its determination of Actual Costs (&#8220;<b>Actual Cost
      Notice</b>&#8221;), which notice will specify any amounts payable by Tenant. In the event that Tenant, following a review of Landlord&#8217;s calculations of the Actual Cost and the open book records as set forth in this Work Letter, disagrees with Landlord&#8217;s
    determination of the Actual Costs, then within thirty (30) days of receipt of Landlord&#8217;s Actual Cost Notice, Tenant will provide written notice to Landlord of its questions, objections or alternative determination of the Actual Costs. Following
    Tenant&#8217;s delivery of its determination of the Actual Cost and delivery of written notice thereof to Landlord, Landlord will agree or disagree in writing within sixty (60) days of receipt of Tenant&#8217;s notice, or the parties will mutually agree in writing
    on the amount of the Actual Cost. Landlord and Tenant agree to cooperate with each other in good faith to resolve any disputes with regard to the Actual Cost. If the parties are unable to mutually agree on the Actual Cost within one hundred eighty
    (180) days of the Actual Cost Notice, then either party may elect to have the matter submitted to the Expedited Arbitration Process (as defined below). Each of Landlord and Tenant will submit to the arbitrator its proposed Actual Cost. The arbitrator,
    in good faith, will select which Actual Cost is correct, but the arbitrator will have no other authority to bind the parties. In no event will the Cost Estimate or the Actual Cost include any costs that do not constitute Allowable Costs.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">If, notwithstanding Landlord&#8217;s diligent and good-faith efforts, Landlord is not able to or does not obtain an Actual Cost in time to reflect such Actual Cost on the
    Actual Cost Notice, Landlord may, within one (1) year after Substantial Completion and notwithstanding the final determination of Actual Cost pursuant to the preceding paragraph, deliver written notice of such Actual Cost to Tenant, and Tenant shall
    pay such Actual Cost to Landlord within thirty (30) days of receipt of such notice.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Audit</u>. Landlord&#8217;s performance of the
    Landlord&#8217;s Work will be administered on an &#8220;open book&#8221; arrangement relative to its costs. Landlord will keep, and cause General Contractor to keep, detailed records of the progress of the Landlord&#8217;s Work performed, administration, and management of the
    Construction Contract (and any subcontracts), and the cost of the Landlord&#8217;s Work as may be necessary for proper financial management under this Work Letter and to substantiate all costs incurred (the &#8220;<b>Work Records</b>&#8221;). Such Work Records will be
    preserved until expiration of the Audit Period (as defined below), or for such longer period as may be required by applicable laws. Landlord will provide, and cause General Contractor to provide, Tenant with access to and the right to inspect and copy
    the Work Records. Landlord will keep full and detailed accounts and exercise such controls as may be reasonably necessary for proper financial management, using accounting and control systems in accordance with GAAP. Tenant will be permitted to review
    and audit (at its sole expense) the Work Records for a period of the longer of (i) twelve (12) months following completion of the Landlord&#8217;s Work, or (ii) the period set forth in the Construction Contract (the &#8220;<b>Audit Period</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">7.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Monthly Rent</u>. The first installment(s) of Base
    Rent shall be based on the Cost Estimate, and the parties shall reconcile such amount once the Actual Cost is determined pursuant to <u>Section 7.2</u> above. After the determination of the Actual Cost occurs pursuant to <u>Section&#160;7.2</u> above,
    Landlord and Tenant will enter into a lease amendment to set forth a Base Rent schedule based on Base Rent for the first twelve (12) months of the Term in the amount that is equal to 7.9% of the Actual Costs; such Base Rent shall thereafter be subject
    to increases as set forth in <u>Section&#160;5</u> of the Lease. Any underpayment or overpayment in the first installment(s) of Base Rent which was based on the Cost Estimate will be reconciled through the next payment of Base Rent due after the
    determination of the Actual Costs.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif"><b>8.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Construction
        of Tenant&#8217;s Work and Alterations</u></b>. Tenant shall perform no Tenant&#8217;s Work except through the General Contractor and in strict accordance with this Work Letter. Any Alterations shall be performed only by a contractor reasonably approved by
    Landlord and subject to Section 7 of the Lease. The contractor performing any work or Alterations on behalf of Tenant shall, for purposes of this Work Letter be referenced as the &#8220;<b>Tenant&#8217;s Contractor</b>.&#8221; In no event shall Tenant be permitted to
    perform Tenant&#8217;s Work prior to providing all information reasonably requested by Landlord relating thereto. Failure by Tenant to provide any information reasonably requested by Landlord, including but not limited to evidence of Tenant&#8217;s and Tenant&#8217;s
    Contractor&#8217;s compliance with all of the insurance requirements hereof, shall constitute a default under this Lease in the event Tenant proceeds with such work. Violations of Landlord&#8217;s rules, regulations, and requirements as set forth herein or as
    otherwise established by Landlord shall constitute a default under this Lease if not corrected by Tenant and/or Tenant&#8217;s Contractor within forty-eight (48) hours of notice, either written or oral, by Landlord to Tenant. Landlord shall have the right to
    post a notice of non-responsibility at a prominent location within the Premises. Any such work will be subject to all of the provisions of this Work Letter including, specifically, and without limitation, this Section (and the subsections hereof) and <u>Section







      9</u> below. It shall be the responsibility of Tenant to enforce the following requirements of Tenant&#8217;s Contractor, and all subcontractors of Tenant&#8217;s Contractor, at every level:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.1<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s Contractor shall be responsible for the
    repair, replacement, and clean-up of any damage by it to other contractor&#8217;s work that specifically includes access ways to the Premises that may be concurrently used by others. Fire lanes, sidewalks, and access to other tenants&#8217; suites may not be
    blocked or obstructed at any time.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.2<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s Contractor shall contain its storage of
    materials and its operations within the Premises and such other space as it may be reasonably assigned by Landlord. Should it be assigned space outside of the Premises, it shall move to such other space as Landlord shall reasonably direct from time to
    time to avoid interference or delays with other work. Tenant&#8217;s Contractor shall park construction vehicles in areas reasonably designated by Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.3<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>All trash and surplus construction materials shall be
    maintained or stored within the Premises and shall be promptly removed from the Premises on a regular basis consistent with first-class project practices. Tenant&#8217;s Contractor shall not use common area trash enclosures or waste bins for disposal of
    trash or surplus construction material and shall be responsible for the proper disposal, off-site, of all such trash and surplus construction material.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.4<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>For any work reasonably anticipated to last for more
    than three (3) days, Tenant&#8217;s Contractor shall provide temporary utilities, portable toilet facilities and portable drinking water as required for its work within the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.5<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Noise shall be kept to a minimum at all times, and
    shall not be permitted to materially or unreasonably interfere with the conduct of other tenant&#8217;s business, or the general operation of the Project. Tenant&#8217;s Contractor shall notify and obtain approval from Landlord&#8217;s Representative of any planned work
    to be done on Sundays.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.6<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant and Tenant&#8217;s Contractor are responsible for
    compliance with all applicable codes and regulations of duly-constituted authorities having jurisdiction as far as the performance of the Tenant&#8217;s Work is concerned and for all applicable safety regulations established by the Landlord, OSHA, Cal-OSHA
    or other regulatory agencies, and Tenant further agrees to indemnify, defend, and save and hold Landlord harmless for claims arising from Tenant&#8217;s Work. Prior to commencement of construction, Tenant shall submit to Landlord evidence of insurance as
    required by this Lease (including, if applicable, course of construction coverage) and evidence of insurance for Tenant&#8217;s Contractor reasonably satisfactory to Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.7<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s Contractor shall not post signs on any part
    of the Project nor on the Premises, without Landlord&#8217;s prior written approval.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.8<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall be responsible for and shall obtain and
    record a Notice of Completion following completion of Tenant&#8217;s work.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.9<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>All required permits and approvals, including but not
    limited to Planning, Building, Fire, and Health department permits, must be obtained and all necessary calculations, including, but not limited to, those required under Title&#160;24, must be submitted to the local governing agencies for all work to be
    performed by Tenant or Tenant&#8217;s Contractor in the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.10<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>No modifications to the exterior of the Building shall
    be permitted without Landlord&#8217;s approval. No romex wiring or asbestos-containing materials shall be allowed, nor shall water lines be placed in slabs, unless approved by Landlord prior to installation. All equipment placed upon the roof as a result of
    the Tenant&#8217;s Work, and all roof penetrations shall be approved by Landlord prior to the commencement of work.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">8.11<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord, in Landlord&#8217;s reasonable discretion, may
    from time to time establish such other reasonable non-discriminatory rules and regulations for protection of property and the general safety of occupants and invitees of the Project. Such rules and regulations shall be provided to Tenant in writing and
    shall apply to Tenant and Tenant&#8217;s Contractor as though established upon the execution of the Lease; provided, however, in no event shall such rules cause a material increase in Tenant&#8217;s costs, cause any delays in the completion of Landlord&#8217;s Work or
    TI Work or otherwise interfere with Tenant&#8217;s access to the site or completion of the TI Work.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif"><b>9.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Coordination
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    shall coordinate the Tenant&#8217;s Work with any construction schedule for any work being performed by or on behalf of Landlord or any other tenant, and that the performance of the Tenant&#8217;s Work shall not materially interfere with Landlord&#8217;s construction
    activities. If there be such material interference or conflict, notice thereof shall be given to Tenant, and immediately after receipt of such notice the Tenant agrees to cease or cause to be terminated such material interference or conflict. Further,
    should Tenant delay Landlord&#8217;s work at the Premises or any other area of the Building or Project due to the construction of Tenant&#8217;s Work, Tenant shall be responsible to Landlord for any lost rents due to the delay of the commencement of any lease for
    premises within the Project. Tenant further covenants and agrees that Tenant and Tenant&#8217;s Contractor shall comply with all rules and regulations promulgated by Landlord, or its agent, and all directives of Landlord governing construction or
    installation activities, including but not limited to, permissible hours for construction or installation activities, storage of equipment and responsibility for cleaning of work areas, provided that all such rules or directives shall be provided to
    Tenant in writing. If Tenant or Tenant&#8217;s Contractor shall fail to comply with the provisions of this Section any costs actually incurred by Landlord as a result of such failure shall be at Tenant&#8217;s sole and exclusive expense, payable upon demand.
    Tenant shall indemnify, defend, and hold Landlord harmless from and against any and all actions, claims, costs, demands, expenses, and liabilities arising out of or relating to, directly or indirectly, any work undertaken by Tenant or on Tenant&#8217;s
    behalf at the Project.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>10.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Limitation on
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    improvements to the Premises made by Tenant. Tenant hereby acknowledges and agrees that the compliance of the Tenant&#8217;s Work, or other Alterations made to the Premises by the Tenant and any plans therefor, with all applicable governmental laws, codes,
    and regulations shall be solely Tenant&#8217;s responsibility. Landlord assumes no liability or responsibility resulting from the failure of the Tenant to comply with all applicable governmental laws, codes, and regulations or for any defect in any of the
    Tenant&#8217;s Work or other Alteration to the Premises made by Tenant. Tenant further agrees to indemnify, defend, and hold harmless Landlord from any loss, cost, damage or expense incurred, claimed, asserted, or arising in connection with any of the
    foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>11.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Expedited
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    modified as follows: (a)&#160;there will be one arbitrator who is selected utilizing the then-current AAA process and who has at least ten (10) years of relevant experience; (b) the arbitration will be conducted through document submission without a
    hearing; and (c) the arbitrator will issue a final decision within thirty (30) days after confirmation of the appointment of the arbitrator. The arbitrator will have no decision-making authority other than to select either the determination or
    recommendation of Landlord or Tenant as final and conclusive after due consideration of the factors to be taken into account under the applicable provisions of this Lease. The arbitrator&#8217;s determination will be binding upon the parties. The costs and
    fees of the arbitrator will be shared equally by Tenant and Landlord. All deadlines for obligations by either Tenant or Landlord shall be tolled for such period as an Expedited Arbitration Process is proceeding until the arbitrator issues a final
    decision.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>12.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Time of Essence</u></b>.
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif"><b>13.<font style="font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font></b></font><b><u>Miscellaneous</u></b>.
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 8pt Times New Roman,Times,serif; margin: 0px; text-indent: 0px; text-align: center;">Exhibit B </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"> </p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><b>Schedule 1 to Exhibit B</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-variant: small-caps"><b>Landlord&#8217;s Work and TI Site Work Plan</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
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      <tr>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EL CORAZON OBC</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>BUILDING A (PHARMA-X) LANDLORD-TENANT RESPONSIBILITY MATRIX</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><i>Revised following discussions on 3/3/22 and Developer's
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><i>&#160;</i></b></font></p>
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      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Exhibit









              1 - Site Scope of Work</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Dated
              09/13/2022</b></font></td>
        <td colspan="2" style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Attached under separate cover</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Exhibit









              2 - Shell building design parameters</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Dated
              06/09/2022</b></font></td>
        <td colspan="2" style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Attached under separate cover</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Exhibit









              3 - Site / Shell building Utilities</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Dated
              09/20/2022</b></font></td>
        <td colspan="2" style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Attached under separate cover</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Exhibit









              4 - Electric House and Tenant Meters</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Dated
              09/27/2022</b></font></td>
        <td colspan="2" style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Attached under separate cover</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT








              1&#160;</b></font></td>
        <td style="border-bottom: Black 1pt solid; vertical-align: top; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT 2&#160;</b></font></td>
        <td colspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT 3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;EXHIBIT 4</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="5" style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 3pt; padding-left: 3pt; padding-bottom: 10pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps; color: Black"><b>[***]</b></font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt; padding-bottom: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt; padding-bottom: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt; padding-bottom: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding: 3pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding: 3pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>DESCRIPTION</b></font></td>
        <td colspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding: 3pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>RESPONSIBILITY</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding: 3pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SCA COMMENTS</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding: 3pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SUDBERRY COMMENTS</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding: 3pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>TENANT REQUESTED CHANGES</b></font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>LANDLORD COST</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Provided by LL as part of Lease Cost</b></font></p>
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        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>TENANT COSTS</b></font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>subject to payment from Landlord's Contribution and/or the Moving
                Allowance, and subject to caps on FF&amp;E Costs &amp; the Moving Allowance"</b></font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SHELL COST BUT TI BUILT
              (Treated as a Shell Cost but constructed under the TI permit)</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>IN BLUE </b><br>
            <b>BELOW</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>IN ORANGE BELOW</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>IN MAGENTA BELOW</b></font></td>
      </tr>

  </table>
  <p style="margin: 0">&#160;</p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin: 0"> </p>
  <p style="margin: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin: 0"><font style="color: Black">&#160;</font></p>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="7" style="border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Type IA Structure(West Building) 103,000 SF
              footprint w/ 42,600 SF mezzanine (Includes approx. 95,900 sf R&amp;D, 15,100 sf Warehouse and 34,600 sf unoccupied mechanical mezz)</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>5/25: Mezz SF revised to 42,600 SF</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">CODE REQUIREMENTS FOR FIRE RATING</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Fire Rating Requirements for Building Elements (code):</u></b></font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roof construction - 1.5 hour</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Exterior bearing walls - 3 hours</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior bearing walls - 3 hours</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Floor construction (including mezzanines) - 2 hours</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Design Parameters (West
              Building):</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">PRIMARY STRUCTURAL FRAME</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Primary Structural frame:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Steel structure w/ 3-hour monokote.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Wide flange section proposed due to anticipated loads and requirements
              for fireproofing"</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EXTERIOR BEARING WALLS</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Exterior Bearing Walls:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Concrete tilt walls - minimum 6.5"" thick for 3 hour rating</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><strike>Design and construct
              the pop-out loading areas on north and south to be removeable in the future</strike></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Openings for man doors,
            roll-up doors and louvers.</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="5" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">MEZZANINE (UNOCCUPIED, MECHANICAL EQUIPMENT ONLY)"</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Mezzanine Floor deck:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Metal deck w/3.25"" lt.wt. concrete over flutes for 2 hour rating</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Mezzanine / second level shall be for mechanical equipment only and
              classified as unoccupied space. Assume 125 lbs./sf live load, minimum</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">c. Major openings in floor shall be coordinated with TI</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">d. Interior shear walls or brace frames as needed at mezzanine</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TI architect shall provide
            locations of major floor openings</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include (2) metal stairs at
            mezzanine</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed.&#160;&#160;(2) Stairs for
            mezz egress shall be part of shell / LL scope</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">One elevator, freight /
            passenger, (2-stop) rated for 10,000 lbs. to mezzanine</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed.&#160;&#160;Dimensions shall
            be coordinated with TI</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Specs Received from CRB on 8/17/2022:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Passenger Elevator</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Capacity: 4000 lbs.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cab: 9'-0&#8221;D by 9'-0&#8221;"H by 7'-0&#8221;"W</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Door: Same width and depth as cab / front</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Stops: 2 - first and second floor"</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">One elevator, freight /
            passenger, (3-stop) rated for 10,000 lbs. to mezzanine and roof (TI architect to confirm capacity)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>7/28/2022:</u>&#160;&#160;Elevator









            added</font></td>
      </tr>
      <tr>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 27%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 9%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

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        <td style="vertical-align: top; width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 27%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Specs Received from CRB on 8/17/2022:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Maintenance Elevator</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Capacity: 4000 lbs. min., prefer higher capacity if in budget</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cab: 9'-0&#8221;D by 10'-0&#8221;H by 7'-0&#8221;W</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Door: Same width and depth as cab / front and rear</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Stops: 3 - first floor, equipment platform, and roof</font></p>
        </td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">ROOF CONSTRUCTION</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt; text-align: left; vertical-align: top">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Roof deck:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Metal deck w/3.25"" lt. wt. concrete over flutes for 1.5 hour rating</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Design to accommodate HVAC loading including strobic fans and equipment screening.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">c. Assume minimum 15 lbs./sf misc. loads for equipment, ceiling support, etc."</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Locations and size of concrete roof pads shall be
              coordinated with TI.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roof screens shall be 12-feet tall max.</font></p>
        </td>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Rooftop will need
            to accommodate PV system as required by City CAP.&#160;&#160;If adequate space&#160;&#160;is not available on the roof for CAP required photovoltaics, an energy portfolio comprising of at least 75% renewable, emissions-free energy may be purchased for the
            remainder, subject to City approval.</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt; text-align: left; vertical-align: top">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Concrete pads for major tenant equipment:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include structural roof pad for equipment with normal weight concrete and roof screens."</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt">
          <p style="margin-top: 0; margin-bottom: 0"></p>
          <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
          <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
          <p style="margin-top: 0; margin-bottom: 0">&#160;<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roofing:&#160;&#160;Rigid insulation over concrete with single ply roofing</font></p>
          <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
          <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">HEIGHTS</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior clear height of
            35-feet to lowest structure at roof</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>From Tenant:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Currently need minimum of 35ft to bottom of structure. Too early to know,
              but expect piping and duct may drive this up an additional 2ft.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">We can coordinate with structural engineer during Design Development.
              However, the El Corazon Specific Plan limits maximum building height to 50-feet (top of parapet) We cannot exceed this height.</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

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        <td rowspan="2" style="vertical-align: top; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior









            clear height reduced in locations of 72-inch deep structural members per discissions with CRB</font></td>
        <td style="vertical-align: top; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Minimum 21-feet floor to
            floor at mezzanine</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="4" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">FLOOR SLAB</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6&#8221; slab <strike>except 8&#8221; at high pile storage</strike></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: red"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><strike>Assume 30,000 sf of 8&#8221; slab</strike></font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TI
            architect to identify location of high pile storage</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><strike>Leaveouts for TI
              underground</strike></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Floor drains and underground
            plumbing</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Recessed slab areas</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SHAFT









            OPENINGS</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Shaft openings for major
            Tenant&#160;&#160;utility risers coordinated with TI.&#160;&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TI
            architect to provide locations and dimensions</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="7" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Type IIB Structure (East Building) 70,000 SF footprint w/ 36,000 sf second floor (includes approx. 75,250 sf Office and 30,750 sf R&amp;D)</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5/25:
            Mezz SF revised to 36,000 SF</font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">CODE









            REQUIREMENTS FOR FIRE RATING</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Fire Rating Requirements for Building Elements (code):</u></b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Primary Structural Frame - none</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roof construction - none (propose 1.5 hr. for future Type 1A)</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Exterior bearing walls - none</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior bearing walls - none</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Floor construction (including mezzanines) - none"</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
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        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Design Parameters (East
              Building):</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">PRIMARY









            STRUCTURAL FRAME</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Primary Structural frame:</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Steel structure. Wide flange sections proposed instead of trusses due to
              anticipated loads and requirements for future conversion to a manufacturing space and Type IA construction (fireproofing required)"</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EXTERIOR BEARING WALLS</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Exterior Bearing Walls:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Concrete tilt walls - minimum 6.5&#8221; thick</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SECOND FLOOR (OFFICE USE)"</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Mezzanine Floor deck:</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Metal deck w/3.25"" lt.wt. concrete over flutes.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Assume all office spaces</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><strike>c. Mezzanine shall be designed to be removed in the future</strike></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">d. Interior shear walls or brace frames as needed at second floor</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">e. Openings in floor coordinated with TI</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Per
            discussions this shall be a second floor integrated into structure. Ability to remove in the future is no longer required</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include (2) metal stairs at
            second floor</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include (1) passenger
            elevator (2-stop, side acting) rated for 5,000 lbs.</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; vertical-align: top; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 27%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 9%; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td rowspan="2" style="vertical-align: top; width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 27%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Specs Received from CRB on 8/17/2022:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Passenger Elevator</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Capacity: 2500 lbs.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cab: Sized to allow for stretcher</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Door: Standard size / front</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Stops: 2 - first and second floor</font></p>
        </td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include
            (1) passenger / freight elevator (2-stop) rated for 10,000 lbs. to roof in Chiller Room (TI Architect to confirm capacity)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>7/28/2022:</u>&#160;&#160;Elevator
            added</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Specs Received from CRB on 8/17/2022:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Maintenance Elevator</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Capacity: 4000 lbs. min., prefer higher capacity if in
              budget</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cab: 9'-0""D by 10'-0""H by 7'-0""W</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Door: Same width and depth as cab / front and rear</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Stops: 2 - first floor and roof"</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="5" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">ROOF CONSTRUCTION </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Roof deck:</u> Allow for future manufacturing space and Type IA
              construction:</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Metal deck w/3"" lt. wt. concrete over flutes for 1.5 hour rating</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Design to accommodate HVAC units, exhaust for labs and office and
              equipment screening.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">c. Assume minimum 15 lbs./sf misc. loads for equipment, ceiling support,
              etc. for future manufacturing</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td rowspan="5" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Rooftop will need
            to accommodate PV system as required by City CAP.&#160;&#160;If adequate space&#160;&#160;is not available on the roof for CAP required photovoltaics, an energy portfolio comprising of at least 75% renewable, emissions-free energy may be purchased for the
            remainder, subject to City approval.</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Concrete pads for major tenant equipment:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Include structural roof pads for equipment with normal weight concrete
              and roof screens.</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Locations and size shall be coordinated with TI.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>From Tenant:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed that equipment (w/curbs) and roof stacks are less than 12-feet</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Single large approx.100-foot
            long skylight on the roof.</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">This
            will limit space available for PV, rooftop equipment</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Additional (3) skylights <b><u>if</u></b>
            adequate space is available for rooftop PV equipment. To be evaluated.</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>7/28/2022:</u>&#160;&#160;Three









            (3) additional skylights requested.&#160;&#160;To be evaluated if this is feasible.</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roofing:&#160;&#160;Rigid insulation
            over concrete with single ply roofing</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="3" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">HEIGHTS</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior
            clear height of 31-feet to lowest structure at roof</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Minimum
            18-feet from floor to floor at mezzanine</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Minimum
            clearance on second level at 13-feet</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td rowspan="2" style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">FLOOR SLAB</font></td>
        <td style="vertical-align: top; width: 28%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6&#8221; slab </font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Recessed slab areas coordinated with TI.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TI architect to provide locations and dimensions.</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>ROOFING (West and East Buildings)</b></font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Single Ply TPO roofing
            proposed</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Industry standard roof
            warranty covering newly installed roofing</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">20 year warranty</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree. </font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Major roof openings for
            Tenant Improvement equipment</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">No base building equipment
            and systems.&#160;&#160;Tenant shall provide locations and sizes of major roof openings</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Will include in shell design
            if information is provided in a timely manner</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roof penetrations for Tenant
            equipment</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>UTILITIES&#160;&#160;(Shell design to extend to site POCs, approx. 5' outside of building)</b></font></td>
      </tr>
      <tr>
        <td rowspan="2" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">WATER</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">4" domestic water service
            (two 2" meters) to the building</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Meet
            city requirements</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree
            subject to City approval</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>6/7/2022:









            </u>&#160;Water service upsized to 4" from 3"</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Reclaimed water for
            landscaping</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">City
            currently doesn't have reclaimed water here but we can install purple pipe.</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="4" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">WASTE</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Landlord
            to&#160;&#160;provide 6" site sewer with (1) POC to West building and (1) POC to East building.&#160;&#160;Minimum invert elevation at East POC shall be 13-feet below finish floor</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">LL will
            provide a single sewer POC on site as noted on Exhibit 3.&#160;&#160;Sewer invert at 13-feet below FF</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6"
            domestic waste lines&#160;&#160;internal to building </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6"
            industrial waste lines&#160;&#160;internal to building with sample port exterior to building</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6"
            process waste line internal to building and process waste neutralization system</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td rowspan="6" style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">DRY UTILITIES</font></td>
        <td style="width: 28%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5 psig/ 36,700 cfh natural gas service to exterior of building</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>7/22/2022:</u>&#160;&#160;Gas load increased from 35,000 cfh to 36,700 cfh</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">8,000 A power at 480V
            electrical utility (two services to two 4000A transformers) with conduit to electrical switchgear within SDGE room. </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SDGE room shall be sized in coordination with TI
              architect.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Space will be provided for sub-panels, disconnect and
              other equipment associated with PV system.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Battery storage, if required, will be in exterior
              equipment yard and LL cost.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">This room will require (2) exit doors. Recommend exterior
              access only, no access from building interior.</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #C87700"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #C87700"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SDGE Room will have house panel for site lighting, EV
              chargers.</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">4,000A service and switchgear to be located at equipment
              yard</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td rowspan="2" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
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            service at equipment yard added</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
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              Service size and location on site TBD</font></p>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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            added to electric service</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel / Data conduit sweeps
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant to provide conduit
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree. </font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
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  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
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      <tr>
        <td rowspan="4" style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">FIRE RISERS</font></td>
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        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Shell will include:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(1) fire riser at west building and</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(1) fire riser at east building.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire risers shall be designed to handle an ESFR system.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire riser room shall be sized in coordination with TI
              architect</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">If City approves all fire sprinkler distribution shall be
              deferred to TI to avoid rework of any piping installed for cold shell.</font></p>
        </td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>UPDATE:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #7030A0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Third Fire riser in equipment yard added to TI scope</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>9/30/22:</u>&#160;&#160;Third









            Fire riser in equipment yard added</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">ESFR at high pile storage</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">See note above</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Extra Hazard at Lab and Mfg.,
            Ordinary Hazard at office space</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">See note above</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SITEWORK</b></font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Landlord shall deliver all
            site utilities, access drives and a certified pad.&#160;&#160;Includes onsite and offsite work required for Building A delivery</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Soil prep as determined /
            directed by Landlord.&#160;&#160;Any increased construction costs attributable to soil conditions shall be borne exclusively by Landlord</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Additional









            sitework costs related to moving building west to be borne by tenant.</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Exterior Amenity Area</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree
            but Tenant needs to state requirements, i.e., shade structures, furniture, decorative concrete, etc.</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td rowspan="2" style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">DOCKS AND SPILL CONTAINMENT</font></td>
        <td style="width: 28%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Concrete paving at loading docks and incline on south side of building for spill containment</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Standard thickness as recommended by Geotech for trucks delivering chemicals</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Spill containment devices and
            treatment</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EV









            CHARGERS</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EV chargers to meet City of
            Oceanside CAP requirements with electrical sized to accommodate future chargers. City CAP requires 15% of parking spaces to be designated EV spaces and Level 2 chargers to be installed for 50% of the EV spaces. </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="5" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">MISC SITE STRUCTURES</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Refuse enclosures</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Truck dock screen walls at
            south and north side of dock</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;14-feet
            high screen</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">30 yard compactor at south
            dock</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>Per Tenant:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">OK to lose (1) truck space</font></p>
        </td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Retaining walls on site
            perimeter as indicated on site plan</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Monument Sign</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant
            shall provide design including power / lighting requirements.&#160;&#160;Design shall be in compliance with signage design approved for Overall El Corazon OBC </font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="2" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EQUIPMENT YARD AND ENCLOSURE</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Screen walls w/ 21-feet screen walls with gates for truck access</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant shall provide maximum height of proposed tanks to confirm that the
              wall provides adequate screening as required by City</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 3pt; padding-left: 3pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>From Tenant:</u></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Maximum Heights of the tanks in the exterior equipment yard</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a. Bulk solvent and waste tanks in NE of yard are 16ft tall. Required
              roof structure will be 30ft tall.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b. Leased nitrogen tanks in SW of yard are planned to be 19ft tall.</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><strike>No roof over these.</strike></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; color: #2E74B5"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roof is required over these tanks</font></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Slab with large retention
            pits for secondary containment </font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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            Tenant</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 28%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Canopies over equipment</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Confirmed the 30-foot canopy over equipment will be TI scope </font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">HAZMAT









            REPORTS AND SIGNAGE</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Exterior Hazardous material
            storage enclosure, relevant signage, Hazardous Material Business Plan (HMBP) as required by City for submission to AHJ and code compliance improvements</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">STORMWATER









            TREATMENT</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Underground detention system</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Project will&#160;&#160;have
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td rowspan="2" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">PARKING</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Parking to comply with City
            of Oceanside requirements</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">No canopies over parking</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">See comments for PV system</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>PHOTOVOLTAICS</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">City of Oceanside Climate
            Action Plan requires building to include renewable energy facilities that supply at least 50-percent of forecasted electricity demand</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">See comment above.&#160;&#160;System
            size and location TBD</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>CORE AREAS</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Main Electrical Room -
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">MPOE Room - Includes conduit
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Electrical distribution rooms
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">IDF closets connected to MPOE</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Finished lobby with Class A
            finishes at building entry only</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">New restrooms, finishes and
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Janitor's closets</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Code required bicycle storage</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Code required signage for
            base building rooms</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>PERMITS AND FEES</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Building Site, Core and Shell
            Permit and Fees</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
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    <div style="TEXT-ALIGN: center">&#160;</div>
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      <tr>
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        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>TENANT AREAS</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Drywall at inside of exterior
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Finishes at inside face of
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Electrical closets within
            Tenant Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel / data rooms within
            Tenant Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fixed casework</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">All specialty equipment
            required by Tenant</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fixtures, Furniture,
            Equipment (FF&amp;E)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Laboratory Equipment
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Chemical Fume Hoods, bench
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Appliances</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">All non-code required
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>PLUMBING</b></font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      </tr>
      <tr>
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  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
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        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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            water plant</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Chilled water pipe risers</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Condenser water capacity</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Condenser water pipe
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Central gas-fired condensing
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Additional / dedicated
            cooling for Tenant requirements</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>ELECTRICAL</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Shell area life safety
            emergency lighting / signage as shown in the Core and Shell Construction Documents</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Lighting and power
            distribution for site lighting as shown in the Core and Shell Construction documents</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree,
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      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
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  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td style="width: 11%; border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 28%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Two 1.5MW emergency generators, ATS and conduit as required</font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="width: 11%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 10%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Uninterruptable Power System
            (UPS)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Distribution, devices and
            fixtures for Tenant Premises </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Lighting and power
            distribution for lobby and restroom areas</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Lighting and power
            distribution for Tenant Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant Premises life safety
            emergency lighting/signage </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant panels, transformers,
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>FIRE PROTECTION</b></font></td>
      </tr>
      <tr>
        <td rowspan="2" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SHELL BUILDING FIRE PROTECTION</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Building shell: fire risers</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Main distribution piping and
            sprinkler heads</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Subject
            to City approval&#160;&#160;all mains, branches and drops to be in the Tenant Improvement.&#160;&#160;This would be the most effective approach so that the shell distribution does not get installed and then modified when Tenant Improvements are installed.&#160;&#160;SCA to
            confirm with City&#160;&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">All lateral piping, drops and
            ceiling sprinkler heads within Tenant Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Pre-action dry-pipe or
            chemical systems (if required in any areas)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire extinguisher cabinets
            and extinguishers at core areas, excluding the Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire extinguisher cabinets
            and extinguishers at Tenant Premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>FIRE ALARM</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Base building Fire Alarm
            system as required for completion of Core &amp; Shell, with devices at elevators &amp; core areas</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Subject
            to City approval,&#160;&#160;all Fire Alarm systems to be designed and installed under the Tenant Improvements</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Agree</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire alarm sub panels and
            devices for Tenant Premises with integration into base building system </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black"> </font></p>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center">&#160;</div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="margin-top: 0; margin-bottom: 0"><font style="color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="8" style="border: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>TELEPHONE / DATA</b></font></td>
      </tr>
      <tr>
        <td style="width: 11%; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="width: 11%; border-bottom: Black 1pt solid; border-right: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="vertical-align: top; width: 10%; border-bottom: Black 1pt solid; border-right: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; width: 9%; border-bottom: Black 1pt solid; border-right: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel/Data pathways from MPOE
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel/Data cabling from MPOE
            room to Tenant tele/data rooms </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fiber optic service for
            Tenant use </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel/data infrastructure
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Provision of circuits and
            service from service providers </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Audio visual systems and
            support</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Station cabling from Tenant
            tel/data room to all Tenant locations, within the suite and exterior to the suite, if needed</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant tele/data rooms</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel/Data pathways from MPOE
            room to Tenant tele/data rooms</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tel/Data cabling from MPOE
            room to Tenant tele/data rooms </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fiber optic service for
            Tenant use </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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            support</font></td>
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Station cabling from Tenant
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td colspan="8" style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SECURITY</b></font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Card access serving main
            building entry points and restricted access areas on Tenant-installed&#160;&#160;and managed system</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Video camera coverage on
            Tenant-installed and managed system </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Manned security station in
            lobby</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Card access serving main
            building entry points and restricted access areas on Tenant-installed&#160;&#160;and managed system</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Video camera coverage on
            Tenant-installed and managed system </font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Manned security station in
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>X</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left; padding-right: 3pt; padding-left: 3pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <p style="margin: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Schedule 1 to Exhibit B</div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0; text-align: justify; text-indent: 0">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0; text-align: justify; text-indent: 0"></p>
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        <td style="border-top: black 1pt solid; border-right: black 1pt solid; border-left: black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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      <tr style="vertical-align: top">
        <td style="border-top: black 1pt solid; border-left: black 1pt solid; padding-right: 5.4pt; padding-left: 0.5in; text-indent: -0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#9679;&#160;&#160;&#160;&#160;&#160;&#160;Hazardous Waste Treatment
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        <td style="border-top: black 1pt solid; border-right: black 1pt solid; border-left: black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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      <tr style="vertical-align: top">
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  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">Exhibit C</div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">2850 2855 &amp; 2859 GAZELLE OWNER (DE) LLC</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>&#8220;Buyer&#8221;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>with Escrow Instructions for</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">FIRST AMERICAN TITLE INSURANCE COMPANY</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>&#8220;Escrow Holder&#8221;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>&#160;</b></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">PROPERTY NAME: IONIS GAZELLE CARLSBAD OAKS NORTH BUSINESS PARK CAMPUS</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>LOCATION: CARLSBAD, CALIFORNIA</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><u>TABLE OF CONTENTS</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="2" style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; border-bottom: Black 1pt solid; text-align: right"><font style="font-size: 10pt">Page</font></td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE I</td>
        <td style="vertical-align: top">CERTAIN DEFINITIONS</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">1</td>
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      <tr>
        <td style="vertical-align: top; width: 4%">&#160;</td>
        <td style="vertical-align: top; width: 10%">Section 1.1</td>
        <td style="vertical-align: top; width: 79%">Definitions</td>
        <td style="vertical-align: top; width: 2%; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; width: 5%; text-align: right">1</td>
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      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 1.2</td>
        <td style="vertical-align: top">Rules of Construction</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">9</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE II</td>
        <td style="vertical-align: top">PURCHASE AND SALE AGREEMENT; PURCHASE PRICE</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">9</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 2.1</td>
        <td style="vertical-align: top">Purchase and Sale Agreement</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">9</td>
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      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 2.2</td>
        <td style="vertical-align: top">Purchase Price</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">9</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 2.3</td>
        <td style="vertical-align: top">Indivisible Economic Package</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">9</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE III</td>
        <td style="vertical-align: top">DUE DILIGENCE ITEMS</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">10</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 3.1</td>
        <td style="vertical-align: top">Due Diligence Items</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">10</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 3.2</td>
        <td style="vertical-align: top">Due Diligence Inspection</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">10</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE IV</td>
        <td style="vertical-align: top">TITLE AND SURVEY</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">15</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 4.1</td>
        <td style="vertical-align: top">Title to Real Property</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">15</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 4.2</td>
        <td style="vertical-align: top">Objections and Certain Exceptions to Title</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">15</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 4.3</td>
        <td style="vertical-align: top">Natural Hazard Expert</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">15</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 4.4</td>
        <td style="vertical-align: top">Title Insurance</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">15</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE V</td>
        <td style="vertical-align: top">ESCROW INSTRUCTIONS</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">16</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 5.1</td>
        <td style="vertical-align: top">Escrow Instructions</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">16</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 5.2</td>
        <td style="vertical-align: top">Designation of Reporting Person</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">16</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE VI</td>
        <td style="vertical-align: top">REPRESENTATIONS AND WARRANTIES OF SELLER</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">17</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 6.1</td>
        <td style="vertical-align: top">Representations and Warranties of Seller</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">17</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 6.2</td>
        <td style="vertical-align: top">Limited Liability</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">20</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 6.3</td>
        <td style="vertical-align: top">Knowledge Parties</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">21</td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><u>TABLE OF CONTENTS</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="2" style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; border-bottom: Black 1pt solid; text-align: right"><font style="font-size: 10pt">Page</font></td>
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      <tr>
        <td style="vertical-align: top; width: 4%">&#160;</td>
        <td style="vertical-align: top; width: 10%">Section 6.4</td>
        <td style="vertical-align: top; width: 79%">Liability of Representations and Warranties</td>
        <td style="vertical-align: top; text-align: right; width: 2%">&#160;</td>
        <td style="vertical-align: bottom; text-align: right; width: 5%">22</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE VII</td>
        <td style="vertical-align: top">REPRESENTATIONS AND WARRANTIES OF BUYER</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">22</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 7.1</td>
        <td style="vertical-align: top">Buyer&#8217;s Representations and Warranties</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">22</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE VIII</td>
        <td style="vertical-align: top">OPERATING COVENANTS</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">23</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 8.1</td>
        <td style="vertical-align: top">Buyer-Seller Lease</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">23</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 8.2</td>
        <td style="vertical-align: top">Warranty Transfer</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">23</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE IX</td>
        <td style="vertical-align: top">CLOSING</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">23</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.1</td>
        <td style="vertical-align: top">Escrow Instructions</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">23</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.2</td>
        <td style="vertical-align: top">Closing</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">24</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.3</td>
        <td style="vertical-align: top">Seller&#8217;s Closing Documents and Other Items</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">24</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.4</td>
        <td style="vertical-align: top">Buyer&#8217;s Closing Documents and Other Items</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">25</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.5</td>
        <td style="vertical-align: top">Prorations and Closing Costs</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">25</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.6</td>
        <td style="vertical-align: top">Brokers</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">26</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.7</td>
        <td style="vertical-align: top">Expenses</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">26</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 9.8</td>
        <td style="vertical-align: top">Tax Protests; Tax Refunds and Credits</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">26</td>
      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">ARTICLE X</td>
        <td style="vertical-align: top">MISCELLANEOUS</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">27</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.2</td>
        <td style="vertical-align: top">Successors and Assigns</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">28</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.3</td>
        <td style="vertical-align: top">Governing Law and Consent to Jurisdiction</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">28</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.4</td>
        <td style="vertical-align: top">Counterparts; Electronic Signatures</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">28</td>
      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><u>TABLE OF CONTENTS</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="2" style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; border-bottom: Black 1pt solid; text-align: right"><font style="font-size: 10pt">Page</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top; width: 4%">&#160;</td>
        <td style="vertical-align: top; width: 10%">Section 10.5</td>
        <td style="vertical-align: top; width: 79%">Entire Agreement</td>
        <td style="vertical-align: top; text-align: right; width: 2%">&#160;</td>
        <td style="vertical-align: bottom; text-align: right; width: 5%">28</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.6</td>
        <td style="vertical-align: top">Severability</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">28</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.7</td>
        <td style="vertical-align: top">Attorney Fees</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">29</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.8</td>
        <td style="vertical-align: top">Payment of Fees and Expenses</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">29</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.9</td>
        <td style="vertical-align: top">No Joint Venture</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">29</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.10</td>
        <td style="vertical-align: top">JUDICIAL REFERENCE</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">30</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.11</td>
        <td style="vertical-align: top">Time of Essence</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">31</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.12</td>
        <td style="vertical-align: top">No Waiver</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">31</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.13</td>
        <td style="vertical-align: top">Not an Offer</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">31</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.14</td>
        <td style="vertical-align: top">No Third Party Beneficiaries</td>
        <td style="vertical-align: top; text-align: right">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">31</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">Section 10.15</td>
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        <td style="vertical-align: bottom; text-align: right">31</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">EXHIBITS</p>
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      <tr style="vertical-align: bottom">
        <td style="width: 10%; font-weight: bold; text-align: left">Exhibit A</td>
        <td style="width: 90%">Description of Land</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="font-weight: bold; text-align: left">Exhibit B</td>
        <td style="text-align: left">List of Due Diligence Items</td>
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      <tr style="vertical-align: bottom">
        <td style="font-weight: bold; text-align: left">Exhibit C</td>
        <td style="text-align: left">Disclosure Items</td>
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      <tr style="vertical-align: bottom">
        <td style="font-weight: bold; text-align: left">Exhibit D</td>
        <td style="text-align: left">Permitted Exceptions</td>
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      <tr style="vertical-align: bottom">
        <td style="font-weight: bold; text-align: left">Exhibit E</td>
        <td>List of Warranties</td>
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      <tr style="vertical-align: bottom">
        <td style="font-weight: bold; text-align: left">Exhibit F</td>
        <td>Form of Deed</td>
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        <td style="font-weight: bold; text-align: left">Exhibit G</td>
        <td style="text-align: left">Intentionally Omitted</td>
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        <td style="font-weight: bold; text-align: left">Exhibit H</td>
        <td style="text-align: left">Assignment and Assumption Agreement</td>
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        <td style="font-weight: bold; text-align: left">Exhibit J</td>
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        <td style="font-weight: bold; text-align: left">Exhibit K</td>
        <td style="text-align: left">Form of Owner&#8217;s Affidavit</td>
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        <td style="text-align: left">Form of APP Escrow Agreement</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>PURCHASE AND SALE AGREEMENT</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 35.95pt">This <b>PURCHASE AND SALE AGREEMENT</b> (as the same may be amended, modified, or supplemented from time to time in
    accordance with the terms hereof, this &#8220;<b>Agreement</b>&#8221;), dated effective for all purposes as of October 20, 2022, is by and between <b>IONIS GAZELLE, LLC</b>, a Delaware limited liability company (&#8220;<b>Seller</b>&#8221;), and <b>2850 2855 &amp; 2859
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">Article I</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">CERTAIN DEFINITIONS</p>
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    forth, such definitions to be applicable equally to the singular and plural forms, and to the masculine and feminine forms, of such terms:</p>
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    controlled by or is under common control with Buyer or Seller, as the case may be. For the purposes of this definition, &#8220;control&#8221; means the possession, direct or indirect, of the power to direct or cause the direction of the management and policies of
    a Person, whether through the ownership of voting securities, by contract or otherwise, and the terms &#8220;controlling&#8221; and &#8220;controlled&#8221; have the meanings correlative to the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 35.95pt">&#8220;<b>Anti-Corruption Laws</b>&#8221; means all anti-bribery and anti-corruption laws, regulations or ordinances applicable to
    Seller, its affiliates and their respective operations from time to time, including without limitation (i) the FCPA, (ii) the Global Magnitsky Act, (iii) the Bribery Act 2010 (U.K.), (iv) legislation adopted in furtherance of the OECD Convention on
    Combating Bribery of Foreign Public Officials in International Business Transactions, (v) the United States Bank Secrecy Act , as amended by the Anti Money Laundering Act of 2020; (vi) the Proceeds of Crime (Money Laundering) and Terrorist Financing
    Act (Canada), (vii) the Corruption of Foreign Public Officials Act (Canada), (viii) the U.K. Bribery Act, (ix) the Canadian Corruption of Foreign Public Officials Act, and (x) the Freezing Assets of Corrupt Foreign Public Officials Act (Canada), in
    each case as the same may be amended from time to time and including all rules, regulations, decrees, administrative orders, circulars, or instructions implementing or interpreting the same.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 35.95pt">&#8220;<b>Anti-Money Laundering, Anti-Terrorism, and Sanctions Laws</b>&#8221; means all anti-money laundering-related laws,
    regulations, and codes of practice applicable to Seller, its affiliates and their operations from time to time, including without limitation (i) the U.S. Money Laundering Control Act of 1986, (ii) the United States Bank Secrecy Act, as amended by the
    Anti Money Laundering Act of 2020, (iii) the United States International Money Laundering Abatement and Anti-Terrorist Financing Act of 2001, (iv) the United States Trading with the Enemy Act, and the regulations promulgated thereunder in 31 CFR
    Subtitle B, Chapter 5, as amended, (v) the International Emergency Economic Powers Act and the regulations promulgated thereunder in 31 CFR Subtitle B Chapter 5, as amended, (vi) the regulations of OFAC and The Financial Enforcement Network (FINCEN) or
    any enabling legislation or executive order relating thereto, (vii) the EU Anti-Money Laundering Directives, (viii) the Patriot Act and (ix) the applicable financial recordkeeping and reporting requirements of the U.S. Currency and Foreign Transaction
    Reporting Act of 1970, as amended, in each case as the same may be amended from time to time and including all rules, regulations, decrees, administrative orders, circulars, or instructions implementing or interpreting the same.</p>
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    the form attached hereto as <u>Exhibit M</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Assignment</b>&#8221; shall have the meaning set forth in <u>Section 9.3(d)</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>BTS Purchase Agreement</b>&#8221; shall mean that certain Purchase and Sale Agreement dated as of the date hereof by and
    between Ionis Pharmaceuticals, Inc., as seller, and Oxford I Asset Management USA Inc., as buyer, with respect to the BTS Parcel.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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    required by applicable law to be closed in the States of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Buyer</b>&#8221; shall have the meaning set forth in the preamble.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Buyer Designated Person</b>&#8221; shall have the meaning set forth in <u>Section 6.3(b)</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Buyer Parties</b>&#8221; means, collectively, Buyer, any Affiliates of Buyer, and their actual and potential investors,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Buyer-Seller Lease</b>&#8221; means that certain Lease Agreement between Buyer and Seller in the form attached hereto as <b><u>Exhibit








        N</u></b> and to be entered into and dated as of the Closing Date, whereby Seller shall lease all of the Property from Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Control</b>&#8221; means, with respect to any Person, the possession, directly or indirectly, of the power to direct or cause
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Costs</b>&#8221; shall have the meaning set forth in <u>Section 10.8</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Data Room</b>&#8221; shall have the meaning set forth in <u>Section 3.1(a)</u></p>
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    Compensation and Liability Act of 1980, as amended (&#8220;<b>CERCLA</b>&#8221;), 42 U.S.C. &#167;9601 et seq.; the Toxic Substance Control Act, 15 U.S.C. &#167;2601 et seq.; the Hazardous Materials Transportation Act, 49 U.S.C. &#167;5101 et seq.; the Resource Conservation and
    Recovery Act, 42 U.S.C. &#167;6901, et seq.; the Clean Water Act, 33 U.S.C. &#167;1251 et seq.; the Safe Drinking Water Act, 42 U.S.C. &#167;300f et seq.; the Clean Air Act, 42 U.S.C. &#167;7401 et seq.; Federal Water Pollution Control Act, 33 U.S.C. &#167;&#167; 1251 <u>et seq</u>.;








    Clean Air Act, 42 U.S.C. &#167;&#167; 7401 <u>et seq.</u>; Emergency Planning and Community Right-To-Know Act, 42 U.S.C. &#167;&#167; 11001 <u>et seq.</u>; Occupational Safety and Health Act, 29 U.S.C. &#167;&#167; 65 <u>et</u>&#160;<u>seq.</u>; Occupational Safety and Health Act, 29
    U.S.C. &#167;&#167; 65 <u>et seq.</u>; California Hazardous Substance Account Act, California Health &amp; Safety Code &#167;&#167; 25300 <u>et seq.</u>; California Asbestos Notification Laws, California Health &amp; Safety Code &#167;&#167; 25915 <u>et seq.</u>; California
    Hazardous Waste Control Law, California Health &amp; Safety Code &#167;&#167; 22100 <u>et seq.</u>; California Hazardous Materials Release Response Plans and Inventory Act, California Health &amp; Safety Code &#167;&#167; 25500 <u>et seq.</u>; California Clean Air Act,
    California Health &amp; Safety Code &#167;&#167; 39608 <u>et seq.</u>; California Toxic Pits Cleanup Act, California Health &amp; Safety Code &#167;&#167; 25208 <u>et seq.</u>; California Pipeline Safety Act, California Government Code &#167;&#167; 51010 <u>et seq.</u>;
    California Toxic Air Contaminants Law, California Health &amp; Safe Code &#167;&#167; 39650 <u>et seq.</u>; California Porter-Cologne Water Quality Act, California Water Code &#167;&#167; 13000 <u>et seq.</u>; California Toxic Injection Well Control Act, California
    Health &amp; Safety Code &#167;&#167; 25159.10 <u>et seq.</u>; California Underground Storage Tank Act, California Health &amp; Safety Code &#167;&#167; 25280 <u>et seq.</u>; California Occupational Carcinogens Control Act, California Labor Code &#167;&#167; 9000 <u>et seq.</u>,
    and all other applicable federal, state and local laws, regulations, ordinances, rules and orders that are equivalent or similar to the laws recited above, or otherwise relate to human health, natural resources or the environment, in each case together
    with their implementing regulations, guidelines, rules or orders, and all state, regional, county, municipal and other local laws, regulations, ordinances, rules or orders that are equivalent or similar to the federal and state laws recited above.</p>
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    product or similar privilege, which constitute attorney communications, or which are subject to a confidentiality agreement or that Seller is legally required to not disclose, (b) all cash on hand or on deposit in any operating account or other account
    maintained in connection with the ownership, operation or management of the Real Property, (c) all Trade Fixtures, (d) furniture and equipment located on the Real Property (other than Fixtures), (e) all other personal property placed in the Real
    Property by Seller and used in connection with Seller&#8217;s trade or business and not otherwise necessary for the operation of the Real Property, (f) any licenses, permits and authorizations presently or hereafter issued to or for the benefit of Seller or
    its Affiliates in connection with Seller&#8217;s operation as a going concern and not otherwise necessary for the operation of the Real Property, (g) any intangible property whatsoever related to Seller or its Affiliates as a going concern, and (h) any
    Intellectual Property whatsoever owned or licensed by Seller or its Affiliates. The Excluded Property shall not include plans and specifications for the Improvements owned by Seller.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>&#8220;Grantee&#8221; </b>shall have the meaning set forth in <u>Section 10.16</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Governmental Entity</b>&#8221; means the various federal, state and local governmental and quasi-governmental bodies or
    agencies having jurisdiction over Seller, the Real Property or any portion thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Hazardous Materials</b>&#8221; means (a) any and all substances (whether solid, liquid or gas) defined, listed or otherwise
    classified or regulated as &#8220;hazardous wastes,&#8221; &#8220;hazardous materials,&#8221; &#8220;hazardous substances,&#8221; &#8220;toxic substances,&#8221; &#8220;pollutants,&#8221; &#8220;contaminants,&#8221; &#8220;radioactive materials&#8221;, &#8220;toxic pollutants&#8221;, &#8220;solid wastes,&#8221; or other similar designations in, or otherwise
    subject to regulation under the Environmental Laws, and (b) any other substances, constituents or wastes that are subject to Environmental Law, now or hereafter in effect, including but not limited to (A) petroleum, (B) refined petroleum products, (C)
    waste oil, (D) waste aviation or motor vehicle fuel and their byproducts, (E) asbestos, (F) lead in water, paint or elsewhere, (G) radon, (H) Polychlorinated Biphenyls (PCBs), (I) urea formaldehyde, (J) volatile organic compounds (VOC), (K) total
    petroleum hydrocarbons (TPH), (L) benzine derivative (BTEX), (M) poly- and perfluoroalkyl substances, and (N) petroleum byproducts.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Improvements</b>&#8221; means the buildings, structures, appurtenances, and other improvements located on the Land.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Indemnification Cap</b>&#8221; shall have the meaning set forth in <u>Section 6.2</u>.</p>
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    applications, copyright registrations and like protections in each work of authorship and derivative work thereof, whether published or unpublished and whether or not the same also constitutes a trade secret, (b) any trademark and service mark rights,
    whether registered or not, applications to register and registrations of the same and like protections, and all goodwill connected with and symbolized by such trademarks, (c) all patents, patent applications and like protections including without
    limitation improvements, divisions, continuations, renewals, reissues, extensions and continuations-in-part of the same, (d) any and all trade secrets and trade secret rights, including, without limitation, any rights to unpatented inventions, know-how
    and operating manuals, (e) any and all source code, (f) any and all design rights which may be available to such Person, (g) any and all claims for damages by way of past, present and future infringement of any of the foregoing, with the right, but not
    the obligation, to sue for and collect such damages for said use or infringement of the Intellectual Property rights identified herein, and (h) all amendments, renewals and extensions of any of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Known Environmental Condition</b>&#8221; means any Hazardous Materials at, on, under or migrating to or from, or have migrated
    to or from, the Property as of or prior to the Closing as described or referenced in the Due Diligence Items, Disclosure Items or in reports or other documents otherwise publicly available.</p>
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        A</u></b> and which are commonly known as 2850, 2855 and 2859 Gazelle Court, Carlsbad, California, and including but not limited to any easements, appurtenances, license, privileges, rights of way and other rights appurtenant thereto pursuant to
    the Title Commitment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Leases</b>&#8221; means all unexpired leases, subleases, licenses, occupancy agreements, and any other agreements, written or
    oral, for the use, possession, or occupancy of any portions of the Real Property or otherwise relating thereto, together with any renewals, extensions, amendments, modifications or supplements thereto and guarantees thereof and all prepaid rent, tenant
    security deposits and other deposits, if any, thereunder; provided, however, the Leases shall not include the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Licenses and Permits</b>&#8221; means, collectively, all licenses, permits approvals, density rights, development rights,
    certificates, consents, exemptions, decisions, actions, approvals, variances, entitlements, certificates of occupancy, dedications, sewer rights, subdivision maps and entitlements now or hereafter issued, approved or granted by any Governmental Entity
    in connection with the Real Property and operation at the Property, including, without limitation, all curb cut and street opening permits required for vehicular access to and from the Real Property, together with all renewals and modifications
    thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Lien</b>&#8221; means any lien, mortgage, pledge, encumbrance, charge, security interest, adverse claim, liability, interest,
    charge, priority, transfer restriction (other than restrictions under the Securities Act and state securities laws), encroachment, tax, order, equitable interest, option, warrant, right of first refusal, easement, license, servitude, right of way, or
    zoning restriction.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>OFAC</b>&#8221; means the U.S. Department of the Treasury&#8217;s Office of Foreign Assets Control.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>OFAC List</b>&#8221; means any list of prohibited countries, individuals, organizations and entities that is administered or
    maintained by OFAC, including: (i) Section 1(b), (c) or (d) of Executive Order No. 13224 (September 23, 2001) issued by the President of the United States (Executive Order Blocking Property and Prohibiting Transactions with Persons Who Commit, Threaten
    to Commit, or Support Terrorism), any related enabling legislation or any other similar executive orders; (ii) the List of Specially Designated Nationals and Blocked Persons maintained by OFAC, and/or on any other similar list maintained by OFAC
    pursuant to any authorizing statute, executive order or regulation; or (iii) a &#8220;Designated National&#8221; as defined in the Cuban Assets Control Regulations, 31 C.F.R. Part 515.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Owner&#8217;s Affidavit</b>&#8221; shall have the meaning set forth in <u>Section 9.3(g)</u>.</p>
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    Obstruct Terrorism Act (USA PATRIOT ACT) of 2001, as the same was restored and amended by Uniting and Strengthening America by Fulfilling Rights and Ensuring Effective Discipline Over Monitoring Act (USA FREEDOM Act) of 2015 and as the same may be
    further amended, extended, replaced or otherwise modified from time to time, and any corresponding provisions of future laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Permitted Exceptions</b>&#8221; shall have the meaning set forth in <u>Section 4.2</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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    trust, or other entity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Preliminary Report</b>&#8221; shall have the meaning set forth in <u>Section 4.1</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Property</b>&#8221; means all of the Real Property, and all of Seller&#8217;s right, title and interest in and to all tangible and
    intangible assets solely relating to the Real Property, including, without limitation, (a) all warranties, claims, and causes of action, (b) all claims and causes of action arising out of or in connection with the Real Property after the Closing Date
    (but excluding any claims or causes of action of Seller after the Closing arising from its rights under this Agreement or any documents to be delivered at the Closing), (c) the Licenses and Permits, (d) signage rights, utility and development rights
    and privileges, (e) site plans, surveys, environmental and other physical reports, plans and specifications pertaining to the foregoing, and (f) all licenses, covenants and other rights appurtenant to the Land, including, but not limited to, Seller&#8217;s
    right, title and interest in and to all development, density and similar rights, rights-of-way, open or proposed streets, alleys, easements, strips or gores of land adjacent to, in front of, abutting, or adjoining the Land; provided, however, that
    &#8220;Property&#8221; shall not include the Excluded Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Purchase Price</b>&#8221; shall have the meaning set forth in <u>Section 2.2(a)</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Real Property</b>&#8221; means the Land, the Improvements, and the Fixtures.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">&#8220;<b>Sanctions</b>&#8221; means the sanctions laws, regulations, embargoes or restrictive measures administered, enacted or
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Sanctions Authority</b>&#8221; means each of: (i) the United States; (ii) the United Nations; (iii) the European Union; (iv)
    the United Kingdom; (v) Singapore; (vi) Canada; (vii) the respective governmental institutions and agencies of any of the foregoing, including, without limitation, OFAC, the United States Department of State, and Her Majesty&#8217;s Treasury; and (viii) all
    other similar governmental bodies with regulatory authority over Buyer or its affiliates issuing, administering, enacting or enforcing economic sanctions laws, regulations, embargoes or restrictive measures of the nature set out above, from time to
    time.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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    territory which is the subject of country-wide or territory-wide Sanctions (including without limitation Cuba, Iran, North Korea, Sudan, Syria, or the Crimea region of the Ukraine), or (iii) directly or indirectly Controlled by or under common Control
    with any of the foregoing.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Seller Control Affiliate</b>&#8221; means any Person that directly or indirectly Controls, is Controlled by or is under common
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Seller Knowledge Party&#8221;</b> shall have the meaning set forth in <u>Section 6.3(a)</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Seller Parent</b>&#8221; shall have the meaning set forth in <u>Section 10.16</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Seller Significant Owner</b>&#8221; means any Person that directly or indirectly holds an interest of twenty percent (20%) or
    more in Seller.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Seller&#8217;s Required Removal Items</b>&#8221; shall have the meaning set forth in <u>Section 4.2</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Service Contracts</b>&#8221; shall have the meaning set forth in <u>Section 10.16</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>SRO</b>&#8221; means a self-regulatory organization.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Survey</b>&#8221; means a new ALTA survey of the Land and Improvements.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Surviving Obligations</b>&#8221; shall mean any obligations of Buyer or Seller hereunder that expressly state they will
    survive (a) termination of this Agreement and/or (b) Closing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Title Commitment</b>&#8221; shall have the meaning set forth in <u>Section 4.1</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Title Company</b>&#8221; means First American Title National Commercial Services</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Title Documents</b>&#8221; shall have the meaning set forth in <u>Section 4.1</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Title Policy</b>&#8221; shall have the meaning set forth in <u>Section 4.4</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Trade Fixture</b>&#8221; means a piece of equipment placed on the Real Property which is used in Seller&#8217;s trade or business.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Transferor</b>&#8221; shall have the meaning set forth in <u>Section 10.16</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#8220;<b>Unknown Environmental Condition</b>&#8221; means any Hazardous Materials at, on, under or migrating to or from, or having
    migrated to or from, the Property as of or prior to the Closing and not a Known Environmental Condition.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Warranties</b>&#8221; shall have the meaning set forth in <u>Section 6.1(s)</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Warrantor</b>&#8221; shall have the meaning set forth in <u>Section 8.2</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#8220;<b>Warranty Assignment Package</b>&#8221; shall have the meaning set forth in <u>Section 8.2</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 1.2&#160;&#160;&#160;Rules of Construction</b>. Article and section captions used in this Agreement are for convenience only and
    shall not affect the construction of this Agreement. All references to &#8220;Article&#8221; or &#8220;Section&#8221; without reference to a document other than this Agreement, are intended to designate articles and sections of this Agreement, and the words &#8220;herein,&#8221;
    &#8220;hereof,&#8221; &#8220;hereunder,&#8221; and other words of similar import refer to this Agreement as a whole and not to any particular article or section, unless specifically designated otherwise. The use of the term &#8220;including&#8221; means in all cases &#8220;including but not
    limited to,&#8221; unless specifically designated otherwise. No rules of construction against the drafter of this Agreement shall apply in any interpretation or enforcement of this Agreement, any documents or certificates executed pursuant hereto, or any
    provisions of any of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE II</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>PURCHASE AND SALE AGREEMENT; PURCHASE PRICE</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.1&#160;&#160;&#160;Purchase and Sale </b>Agreement. Seller agrees to sell, transfer, assign and convey to Buyer, and Buyer
    agrees to purchase, accept and assume, subject to the terms and conditions stated herein, all of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.2&#160;&#160;&#160;Purchase Price.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Initial Purchase Price</u>. Buyer shall pay Seller the purchase price (&#8220;<b>Purchase Price</b>&#8221;) in immediately
    available funds at Closing. The Purchase Price shall be equal to TWO HUNDRED FIFTY-EIGHT MILLION FOUR HUNDRED THOUSAND AND NO/100 DOLLARS ($258,400,000.00). The Purchase Price, together with such other funds as may be necessary to pay Buyer&#8217;s required
    payments hereunder, subject to closing adjustments, shall be deposited with the Escrow Holder on or before 10:00 a.m. Pacific Time on the Closing Date in accordance with this Agreement. The Purchase Price shall be paid to Seller upon satisfaction of
    all conditions precedent to the Closing as described herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Additional Purchase Price</u>. If the BTS Closing occurs pursuant to the BTS Purchase Agreement, then the
    Purchase Price shall be increased by $5,000,000 (the &#8220;<b>Additional Purchase Price</b>&#8221;), such that the total Purchase Price shall be $ $263,400,000. Provided that the BTS Purchase Agreement is not terminated, Buyer shall be obligated to deposit the
    Additional Purchase Price with the Escrow Holder on or before 2:30 p.m. Pacific Time on the Closing Date and the Additional Purchase Price shall be held and disbursed in accordance with the APP Escrow Agreement. If the Additional Purchase Price is
    released to Seller in accordance with the APP Escrow Agreement, Seller and Buyer shall, for all purposes, treat the Additional Purchase Price as an adjustment to the Purchase Price including for tax purposes and shall prepare and file all tax returns,
    reports, and any other filings consistent with such treatment to the extent permitted by law. This Section 2.2(b) shall survive the Closing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.3&#160;&#160;&#160;Indivisible Economic Package</b>. Buyer has no right to purchase, and Seller has no obligation to sell,
    less than all of the Property, it being the express agreement and understanding of Buyer and Seller that, as a material inducement to Seller and Buyer to enter into this Agreement, Buyer has agreed to purchase, and Seller has agreed to sell, all of the
    Property, subject to and in accordance with the terms and conditions hereof.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE III</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>DUE DILIGENCE ITEMS</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 3.1&#160;&#160;&#160;&#160;&#160;Due Diligence Items.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Prior to the Effective Date, Seller has delivered to Buyer, or made available to Buyer for inspection via an
    online due diligence data room relating to the Property (the &#8220;<b>Data Room</b>&#8221;), the items described on attached <b><u>Exhibit B</u></b> (the &#8220;<b>Due Diligence Items</b>&#8221;); provided, however, that Seller was and is not obligated to deliver any
    Excluded Property to Buyer or make any Excluded Property available for its review. Buyer acknowledges that any and all documents actually in such Data Room have been made available to Buyer. In addition to such items in the Data Room, Seller shall make
    available to Buyer (by electronic means) any such other documents in Seller&#8217;s possession or control which relate to the Property, other than the Excluded Property, which Buyer shall reasonably request; provided, however, if Buyer requests information
    regarding the Excluded Property, then Seller shall, in good faith, consider whether it can make such information available to Buyer and make the same available to Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;All documents, materials, and information furnished to or made available to Buyer pursuant to this Section 3.1 are
    being furnished or made available to Buyer for information purposes only and without any representation or warranty by Seller with respect thereto, express or implied, except that, to Seller&#8217;s knowledge, they are in all material respects true, correct
    and complete originals or copies of the version of such materials Seller has in its files, and except as may otherwise be expressly set forth in Article VI and elsewhere in this Agreement and any other document delivered at Closing by Seller to Buyer,
    and as limited by Section 6.2, and all such documents, materials, and information are expressly understood by Buyer to be subject to the confidentiality provisions of Section 3.2(e).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 3.2&#160;&#160;&#160;&#160;&#160;Due Diligence Inspection.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Due Diligence</u>. The parties acknowledge and agree that Buyer had the opportunity to analyze the feasibility
    of its ownership, operation, and use of the Property prior to the Effective Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Confidentiality</u>. Buyer and Seller previously agreed that prior to the Closing Buyer and Seller were each
    (and Buyer was obligated to cause the Buyer Parties to) maintain in confidence all non-public information concerning the Property which Seller or its representatives disclosed or delivered to Buyer and/or the Buyer Parties, including, but not limited
    to, (i) any Due Diligence Items and information provided by Seller to Buyer or the Buyer Parties in the conduct of its due diligence or that was posted to the diligence website, and (ii) the results of any inspections of the Property conducted by Buyer
    prior to the Closing Date (collectively, the &#8220;<b>Confidential Information</b>&#8221;), and, shall not, without Seller&#8217;s prior written consent, which may be withheld in Seller&#8217;s sole and absolute discretion, deliver or disclose the same, or any part thereof,
    to any other Person or entity except as may be required by applicable law, regulation or legal process; provided, however, Buyer and Seller were able to disclose any such confidential information to its agents, attorneys, advisors, consultants,
    prospective lenders or investors, and employees involved in the review and inspection of the Property or as may be required by law or by any court or administrative order. For the avoidance of doubt, &#8220;Confidential Information&#8221; shall not include: (i)
    information already in Buyer&#8217;s or any Buyer Parties&#8217; possession prior to its receipt thereof from Seller or its representative; (ii) information which is obtained by Buyer or any Buyer Parties from a third person who is not prohibited from disclosing
    such information to it by any contractual, legal or fiduciary obligation to Seller; (iii) information which is or becomes publicly disclosed through no fault of the Buyer or any Buyer Parties; or (iv) information which is required to be disclosed by a
    court of competent jurisdiction in connection with any litigation between the parties hereto. Notwithstanding the foregoing, Buyer was permitted to disclose and deliver Confidential Information to the Buyer Parties on a need to know basis. Buyer was
    neither allowed to use nor permit the Buyer Parties to use any of the Confidential Information for any purpose other than the evaluation of the Property and the transaction described herein. Notwithstanding anything to the contrary in this Agreement,
    neither Seller nor Buyer was permitted to release or permit to be released any press release or other similar communication relating to the transaction contemplated by this Agreement before the Effective Date without the prior written consent of the
    other party; provided that following the Effective Date and following the filing by Seller or its Affiliates of any filing required to be made by Seller or such Affiliate with the Securities and Exchange Commission with respect to the closing of the
    transaction, Buyer shall be permitted to issue a press release in the form attached hereto as Schedule 3.2(b). Nothing in this Section 3.2(b) shall be deemed to void, supersede, or modify any other confidentiality, nondisclosure or similar agreements
    entered into between Buyer and Seller prior to the Effective Date hereof. The provisions of this Section 3.2(b) shall survive the Closing.</p>
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    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">10</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>AS-IS</u>. Buyer hereby acknowledges that except as is otherwise expressly provided in this Agreement and
    subject to Seller&#8217;s representations and warranties expressly set forth herein, or in any other documents delivered to Buyer upon the Closing (each such document, a &#8220;<b>Closing Document</b>&#8221;), it is relying upon its own inspections, investigations and
    analyses of the Property in entering into this Agreement and, except as otherwise provided in this Agreement or in any Closing Document, and subject to Seller&#8217;s covenants, representations and warranties expressly set forth herein and in any Closing
    Document, is not relying in any way upon any representations, statements, agreements, warranties, studies, reports, descriptions, guidelines or other information or material furnished by Seller or its representatives, whether oral or written, express
    or implied, of any nature whatsoever regarding any such matters, including, without limitation, as to the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;The condition, value, nature, or quality of the Property, including any construction on the
    Property and any materials or systems incorporated into the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(ii)&#160;&#160;&#160;&#160;&#160;&#160;The soil, water or geology relating to the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(iii)&#160;&#160;&#160;&#160;&#160;Any income to be derived from the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(iv)&#160;&#160;&#160;&#160;&#160;The suitability of the Property for any activities or uses which Buyer may wish to conduct on
    or relating to the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(v)&#160;&#160;&#160;&#160;&#160;&#160;The zoning or developability of the Property.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(vi)&#160;&#160;&#160;&#160;&#160;Compliance of the Property or its operation with any law, ordinance, rule, regulation, or the
    status of any permits or approvals relating to or required in connection with the Property, including without limitation the Americans with Disabilities Act, 42 U.S.C. &#167;12101 et seq. (or any successor statute or similar state and local laws).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; margin-left: 0.5in; text-align: justify">(vii)&#160;&#160;&#160;&#160;The presence or absence of any Hazardous Materials on or about the Property or in the vicinity
    of the Property or the compliance of the Property with Environmental Laws; and Buyer expressly acknowledges that the Property Documents constitute written notice to Buyer as may be required by California Health and Safety Code Section 25359.7.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Buyer specifically acknowledges and agrees that, to the extent Seller has made or in the future makes any information (including without
    limitation the Due Diligence Items) regarding any aspect of the Property available to Buyer, Seller has done or will be doing so only as an accommodation to Buyer and that, except as expressly provided elsewhere in this Agreement and in any Closing
    Document, and subject to Seller&#8217;s express covenants, representations and warranties in this Agreement and the Closing Documents, Seller has not made, is not making, and shall make no representation or warranty of any nature concerning the accuracy or
    completeness of Seller&#8217;s files or concerning the authenticity, source, accuracy or completeness of any information contained in them or furnished or to be furnished by Seller to Buyer (including without limitation the Due Diligence Items). As to
    certain of the materials furnished to Buyer from Seller&#8217;s files, Buyer specifically acknowledges that they have been prepared by third parties with whom Seller has no privity and Buyer acknowledges and agrees that no warranty or representation, express
    or implied, has been made, nor shall any be deemed to have been made, to Buyer either by Seller or by any third parties that prepared the materials in question, except as otherwise provided in this Agreement and in any Closing Document and subject to
    Seller&#8217;s express representations and warranties in this Agreement and the Closing Documents. Except as otherwise provided in this Agreement, in any Closing Document and subject to the Excluded Claims, Buyer waives any claim of any nature against Seller
    if any information, conclusion, projection, or other statement of any nature contained in any of those materials should prove not to be true, complete, or accurate for any reason. By its execution of this Agreement, Buyer acknowledges and agrees that a
    material inducement to Seller&#8217;s decision to sell the Property to Buyer at the Purchase Price provided in this Agreement was Buyer&#8217;s agreement to conduct its own feasibility studies and purchase the Property in an &#8220;AS-IS&#8221; condition, subject to the
    express covenants, representations and warranties of Seller set forth in this Agreement or in any Closing Document. Subject to the express covenants, representations and warranties of Seller set forth in this Agreement or in any Closing Document, Buyer
    acknowledges and agrees that it shall accept the Property in its condition as of the Closing.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Liability for Information</u>. Buyer represents that it is a knowledgeable, experienced and sophisticated
    buyer of real estate, and that it is relying solely on the express representations and warranties of Seller made in this Agreement and any other Closing Document, its own expertise, and that of Buyer&#8217;s consultants in purchasing the Property. ANY
    INFORMATION PROVIDED OR TO BE PROVIDED WITH RESPECT TO THE PROPERTY IS SOLELY FOR BUYER&#8217;S CONVENIENCE AND WAS OR WILL BE OBTAINED FROM A VARIETY OF SOURCES. SELLER HAS NOT MADE ANY INDEPENDENT INVESTIGATION OR VERIFICATION OF SUCH INFORMATION AND MAKES
    NO (AND EXPRESSLY DISCLAIMS ALL) REPRESENTATIONS AS TO THE ACCURACY OR COMPLETENESS OF SUCH INFORMATION (EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS AGREEMENT AND THE CLOSING DOCUMENTS). EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS AGREEMENT
    AND THE CLOSING DOCUMENTS AND THE EXCLUDED CLAIMS, SELLER SHALL NOT BE LIABLE FOR ANY MISTAKES, OMISSIONS, MISREPRESENTATION OR ANY FAILURE TO INVESTIGATE THE PROPERTY NOR SHALL SELLER BE BOUND IN ANY MANNER BY ANY VERBAL OR WRITTEN STATEMENTS,
    REPRESENTATIONS, APPRAISALS, ENVIRONMENTAL ASSESSMENT REPORTS, OR OTHER INFORMATION PERTAINING TO THE PROPERTY OR THE OPERATION THEREOF, FURNISHED BY (A) SELLER, (B) ANY PARTNERSHIP, LIMITED LIABILITY COMPANY, CORPORATION, TRUST OR OTHER ENTITY THAT
    HAS OR ACQUIRES A DIRECT OR INDIRECT INTEREST IN SELLER, (C) ANY DIRECT OR INDIRECT MEMBER, MANAGER, MANAGING MEMBER, PARTNER, ADVISOR, TRUSTEE, BENEFICIARY, DIRECTOR, OFFICER, SHAREHOLDER, EMPLOYEE, PARTICIPANT, REPRESENTATIVE OR AGENT IN OR OF SELLER
    OR OF ANY ENTITY THAT HAS OR ACQUIRES A DIRECT OR INDIRECT INTEREST IN SELLER, OR (D) ANY REAL ESTATE BROKER, AGENT, OR OTHER PERSON OR ENTITY ACTING ON SELLER&#8217;S BEHALF. EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS AGREEMENT AND THE CLOSING
    DOCUMENTS, BUYER WILL ACQUIRE THE PROPERTY SOLELY ON THE BASIS OF ITS OWN PHYSICAL AND FINANCIAL EXAMINATIONS, REVIEWS AND INSPECTIONS AND THE TITLE INSURANCE PROTECTION AFFORDED BY THE TITLE POLICY. EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT OR
    THE CLOSING DOCUMENTS (INCLUDING, WITHOUT LIMITATION, SELLER&#8217;S REPRESENTATIONS AND WARRANTIES HEREIN AND THEREIN), SELLER SPECIFICALLY DISCLAIMS, AND NEITHER IT NOR ANY OTHER PERSON IS MAKING, ANY REPRESENTATION, WARRANTY OR ASSURANCE WHATSOEVER TO
    BUYER AND NO WARRANTIES OR REPRESENTATIONS OF ANY KIND OR CHARACTER, EITHER EXPRESS OR IMPLIED, ARE MADE BY SELLER OR RELIED UPON BY BUYER WITH RESPECT TO THE STATUS OF TITLE TO OR THE MAINTENANCE, REPAIR, CONDITION, DESIGN OR MARKETABILITY OF THE
    PROPERTY, OR ANY PORTION THEREOF, INCLUDING BUT NOT LIMITED TO (i) ANY IMPLIED OR EXPRESS WARRANTY OF MERCHANTABILITY, (ii) ANY IMPLIED OR EXPRESS WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE, (iii) ANY IMPLIED OR EXPRESS WARRANTY OF CONFORMITY TO
    MODELS OR SAMPLES OF MATERIALS, (iv) ANY RIGHTS OF BUYER UNDER APPROPRIATE STATUTES TO CLAIM DIMINUTION OF CONSIDERATION, (v) ANY CLAIM BY BUYER FOR DAMAGES BECAUSE OF DEFECTS, WHETHER KNOWN OR UNKNOWN, WITH RESPECT TO THE IMPROVEMENTS OR THE PERSONAL
    PROPERTY, AND (vi) THE FINANCIAL CONDITION OR PROSPECTS OF THE PROPERTY, IT BEING THE EXPRESS INTENTION OF SELLER AND BUYER THAT, EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, THE PROPERTY WILL BE CONVEYED AND TRANSFERRED TO BUYER IN ITS PRESENT
    CONDITION AND STATE OF REPAIR, &#8220;AS IS&#8221; AND &#8220;WHERE IS&#8221;, WITH ALL FAULTS. BUYER, WITH BUYER&#8217;S COUNSEL, HAS FULLY REVIEWED THE DISCLAIMERS, RELEASES AND WAIVERS SET FORTH IN THIS AGREEMENT, AND UNDERSTANDS THE SIGNIFICANCE AND EFFECT THEREOF. BUYER
    ACKNOWLEDGES AND AGREES THAT THE DISCLAIMERS, RELEASES, WAIVERS AND OTHER AGREEMENTS SET FORTH HEREIN ARE AN INTEGRAL PART OF THIS AGREEMENT, AND THAT SELLER WOULD NOT HAVE AGREED TO SELL THE PROPERTY TO BUYER FOR THE PURCHASE PRICE WITHOUT THE
    DISCLAIMERS, RELEASES, WAIVERS AND OTHER AGREEMENTS SET FORTH IN THIS AGREEMENT.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Release by Buyer</u>. Notwithstanding any other provisions contained herein, or in any Closing Document, to
    the contrary (including, without limitation, any language providing for survival of certain provisions hereof or thereof), Buyer hereby acknowledges and agrees that Seller shall, upon consummation of Closing, be deemed to have satisfied and fulfilled
    all of Seller&#8217;s covenants, indemnities, and obligations contained in this Agreement which do not expressly survive Closing and the documents delivered pursuant hereto, and Seller shall have no further liability to Buyer or otherwise with respect to
    this Agreement, the Property, the transfers contemplated hereby, or any documents delivered pursuant hereto, except to the extent of any obligation or liability Seller may expressly have under this Agreement, the Closing Documents or with respect to
    any Excluded Claim. Except for the Excluded Claims or as otherwise provided in this Agreement or any of the Closing Documents, Buyer hereby waives its right to recover from, and fully and irrevocably releases Seller and its Indemnified Parties from any
    and all Claims other than the Excluded Claims that it may now have or hereafter acquire against any Seller or any of the Indemnified Parties arising from or related to any defects, errors, omissions or other conditions, latent or otherwise, affecting
    the Property. With respect to the release set forth in this Section 3.2, Buyer specifically waives the provision of California Civil Code Section 1542. Section 1542 provides as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 1in; text-align: justify">&#8220;A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS WHICH THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR EXPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE
    RELEASE, WHICH IF KNOWN TO HIM OR HER WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY&#8221;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1.5in">BUYER&#8217;S INITIALS: /s/ <u>KB</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Excluded Claims</u>. Notwithstanding anything to the contrary contained in this Section 3.2 or elsewhere
    in this Agreement, the parties acknowledge and agree that the waivers and releases by Buyer set forth in this Section 3.2 or elsewhere in this Agreement or any Closing Document shall not apply to, limit or affect, and the released Claims shall
    expressly not include, any Claims resulting or arising from any of the following (each, an &#8220;<b>Excluded Claim</b>&#8221;) (i) a breach of any representation or warranty of Seller set forth in this Agreement or any of the Closing Documents, (ii) Seller&#8217;s
    fraud or intentional misrepresentation, (iii) third party tort claims arising prior to the Closing Date, (iv) the Surviving Obligations of Seller including all of Seller&#8217;s indemnity obligations set forth in this Agreement, or (v) obligations or matters
    under the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Survival</u>. The provisions of Sections 3.2(e)-(f) shall survive the Closing or any earlier termination of
    this Agreement and delivery of the Deed.</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE IV</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">TITLE AND SURVEY</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.1 &#160;&#160;&#160;&#160;&#160;&#160;Title to Real Property</b>. Buyer obtained (a) a commitment to issue an owner&#8217;s policy of title
    insurance with respect to the Property issued by the Title Company in favor of Buyer (the &#8220;<b>Title Commitment</b>&#8221;), and (b) copies of all documents referred to on Schedule B of the Title Commitment as exceptions to coverage (the &#8220;<b>Title Documents</b>&#8221;).









    Buyer hereby acknowledges that it has received a preliminary title report (&#8220;<b>Preliminary Report</b>&#8221;) with respect to the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.2 &#160;&#160;&#160;&#160;&#160;&#160;Objections and Certain Exceptions to Title</b>. Buyer agrees to accept title to the Real Property at
    Closing subject to the exceptions set forth on <b><u>Exhibit D</u></b> (the &#8220;<b>Permitted Exceptions</b>&#8221;). Notwithstanding anything to the contrary in this Agreement, Seller will be obligated to remove or cure on or before the Closing, in each case,
    exceptions to title to the Property which are (a) any mortgage liens or other monetary liens affecting the Property (except to the extent created by or arising from the acts or omissions of a Buyer Party), (b) mechanics&#8217; liens, materialmen&#8217;s liens and
    claims of liens for labor materials furnished or supplied to the Property or any portion thereof by or on behalf of Seller or its property manager (if applicable), affecting the Property (except to the extent created by or arising from the intentional
    acts or omissions of a Buyer Party), (c) code violations and other violations with respect to the Property that can be satisfied by payment of a liquidated amount or bonding, (d) encumbrances that have been placed against the Property by, through or
    under Seller after the date of this Agreement without Buyer&#8217;s prior written consent, (e) so called &#8220;standard&#8221; exceptions that can be removed from the Title Policy by Seller&#8217;s delivery of the Owner&#8217;s Affidavit, (f) tax liens for real property taxes and
    assessments which are due and payable or any judgment liens, and (g) any other voluntary or involuntary liens or utility liens created or suffered by Seller (not otherwise covered by clauses (a)-(f)) capable of being cleared from title by the payment
    of a sum certain (the liens described in clauses (a) through (g) are collectively referred to as, &#8220;<b>Seller&#8217;s Required Removal Items</b>&#8221;). Except with respect to Seller&#8217;s Required Removal Items, Seller shall have no obligation whatsoever to expend or
    agree to expend any funds, to undertake or agree to undertake any obligations or otherwise to cure or agree to cure any title objections.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.3 &#160;&#160;&#160;&#160;&#160;&#160;Natural Hazard Expert</b>. Buyer and Seller acknowledge that Seller is required to disclose if any
    portion of the Property lies within a natural hazard area or zone. Buyer and Seller agree that Seller may employ the services of Escrow Holder, a company recommended by Escrow Holder, or an affiliate of Escrow Holder (as so employed, the &#8220;<b>Natural
      Hazard Expert</b>&#8221;) to examine the maps and other information specifically made available to the public by government agencies for the purposes of enabling Seller to fulfill its disclosure obligations with respect to the natural hazards referred to
    above and to report the results of its examination to Buyer and Seller in writing. Prior to the Effective Date, Seller, at its sole cost and expense, provided Buyer with a Natural Hazard Disclosure Statement prepared by a Natural Hazard Expert.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.4 &#160;&#160;&#160;&#160;&#160;&#160;Title Insurance</b>. At Closing, and as a condition thereto for Buyer&#8217;s benefit, the Title Company
    shall issue to Buyer or be irrevocably committed to issue to Buyer a standard coverage ALTA owner&#8217;s form title policy in the form of the Pro Forma (the &#8220;<b>Title Policy</b>&#8221;), in the amount of the Purchase Price, insuring that fee simple title to the
    Real Property is vested in Buyer subject only to the Permitted Exceptions.</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE V</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ESCROW INSTRUCTIONS</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 5.1 &#160;&#160;&#160;&#160;&#160;&#160;Escrow Instructions</b>. The Escrow Holder joins in this Agreement to evidence its agreement to act in
    accordance with the terms and conditions of this Agreement. Further, the following provisions shall control with respect to the rights, duties, and liabilities of the Escrow Holder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Escrow Holder acts hereunder as a depository only and is not responsible or liable in any manner
    whatsoever for the (i) sufficiency, correctness, genuineness, or validity of any written instrument, notice or evidence of a party&#8217;s receipt of any instruction or notice which is received by the Escrow Holder, or (ii) identity or authority of any
    person executing such instruction notice or evidence.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Escrow Holder shall have no responsibility hereunder except for the performance by it in good faith of the
    acts to be performed by it hereunder, and the Escrow Holder shall have no liability except for its own willful misconduct or gross negligence.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Escrow Holder shall be reimbursed on an equal basis by Buyer and Seller for any reasonable expenses
    incurred by the Escrow Holder arising from a dispute with respect to the amount held in escrow, including the cost of any reasonable, out of pocket legal expenses and court costs incurred by the Escrow Holder, should the Escrow Holder deem it necessary
    to retain an attorney with respect to the disposition of the amount held in escrow.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In the event of a dispute between the parties hereto with respect to the disposition of the amount held in
    escrow, the Escrow Holder shall be entitled, at its own discretion, to deliver such amount to an appropriate court of law pending resolution of the dispute.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    are federally insured, or which invest solely in government securities and shall belong to Buyer. Interest earned thereon shall be added to the funds deposited by Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 5.2 &#160;&#160;&#160;&#160;&#160;&#160;Designation of Reporting Person</b>. In order to assure compliance with the requirements of Section
    6045 of the Internal Revenue Code of 1986, as amended (for purposes of this Section 5.2, the &#8220;<b>Code</b>&#8221;), and any related reporting requirements of the Code, the parties hereto agree as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Provided the Escrow Holder shall execute a statement in writing (in form and substance reasonably acceptable
    to the parties hereunder) pursuant to which it agrees to assume all responsibilities for information reporting required under Section 6045(e) of the Code, Seller and Buyer shall designate the Escrow Holder as the person to be responsible for all
    information reporting under Section 6045(e) of the Code (the &#8220;<b>Reporting Person</b>&#8221;). If the Escrow Holder refuses to execute a statement pursuant to which it agrees to be the Reporting Person, Seller and Buyer shall agree to appoint another third
    party as the Reporting Person.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Seller and Buyer hereby agree:</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">16</font></div>
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    requested by the Reporting Person or otherwise required to be provided by a party to the transaction described herein under Section 6045 of the Code; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;to provide to the Reporting Person such party&#8217;s taxpayer identification number and a statement (on Internal
    Revenue Service Form W-9 or an acceptable substitute form, or on any other form the applicable current or future Code sections and regulations might require and/or any form requested by the Reporting Person), signed under penalties of perjury, stating
    that the taxpayer identification number supplied by such party to the Reporting Person is correct.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Each party hereto agrees to retain this Agreement for not less than four (4) years from the end of the calendar year in which the Closing
    occurred, and to produce it to the Internal Revenue Service upon a valid request therefor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE VI</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">REPRESENTATIONS AND WARRANTIES OF SELLER</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><b>Section 6.1&#160;&#160;&#160;Representations and Warranties of Seller</b>. Subject to the provisions of Section 6.2, Seller makes the
    following representations and warranties with respect to the Property:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Status</u>. Seller is a limited liability company duly organized, validly existing and in good standing
    under the laws of the State of Delaware and is qualified to transact business in the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Authority</u>. The execution and delivery of this Agreement (and all ancillary documents delivered pursuant
    hereto including, without limitation, the Closing Documents) by Seller and the performance of its obligations hereunder and thereunder have been or will be duly authorized by all necessary action on the part of Seller, and this Agreement constitutes
    the legal, valid, and binding obligation of Seller, subject to equitable principles and principles governing creditors&#8217; rights generally.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Contravention</u>. The execution and delivery of this Agreement by Seller and the consummation of the
    transactions by Seller contemplated hereby or in the other Closing Documents will not (i) violate any judgment, order, injunction, decree, regulation or ruling of any court or Governmental Entity, or (ii) conflict with, result in a breach of, or
    constitute a default under the organizational documents (including any amendments thereto) of Seller, any note or other evidence of indebtedness, any mortgage, deed of trust or indenture, or any lease or other material agreement or instrument to which
    Seller is a party or by which Seller may be bound.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Suits and Proceedings</u>. Except as set forth on attached <b><u>Exhibit C</u></b>, there are no legal
    actions, suits or similar proceedings at law, in equity, or otherwise pending and served or threatened in writing against Seller (with respect to the Property, as opposed to actions against Seller as a going concern) or the Property which would be
    reasonably likely to adversely affect, individually or in the aggregate, (i) the ability of Seller to perform its obligations hereunder, or (ii) the ownership or operation of the Property.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">17</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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    defined in the Internal Revenue Code of 1986, as amended, and the regulations promulgated thereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Consents</u>. No consent, waiver, approval, or authorization is required from any Person (that has not
    already been obtained) in connection with the execution and delivery of this Agreement by Seller or the performance by Seller of the transactions contemplated hereby.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Condemnation</u>. Seller has no knowledge of and has not received any written notice of any pending or
    contemplated condemnation or action in eminent domain from a Governmental Entity with respect to all or part of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Bankruptcy</u>. Seller has not (i) commenced a voluntary case, or had entered against it a petition, for
    relief under any federal bankruptcy act or any similar petition, order or decree under any federal or state law or statute relative to bankruptcy, insolvency or other relief for debtors, (ii) caused, suffered or consented to the appointment of a
    receiver, trustee, administrator, conservator, liquidator or similar official in any federal, state or foreign judicial or non-judicial proceedings, to hold, administer and/or liquidate all or substantially all of its property, or (iii) made an
    assignment for the benefit of creditors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Governmental Notices</u>. Except as set forth on attached <b><u>Exhibit C</u></b> or included in the Due
    Diligence Items made available on or prior to the Effective Date, Seller has no knowledge of and has not received written notice from any Governmental Entity of (i) any pending or threatened zoning, building, fire, or health code violations or
    violations of other governmental requirements, laws, policies or regulations with respect to the Property that have not previously been corrected, (ii) violations with respect to the Title Documents that have not previously been corrected, or (iii)
    violation of any applicable laws, ordinances, rules, requirements, regulations or codes of any governmental agency, body or subdivision thereof bearing on the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(j)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Contracts</u>. Except as set forth on attached <b><u>Exhibit C</u></b> and any agreements expressly
    disclosed as exceptions on the Title Commitment (collectively, the &#8220;<b>Contracts</b>&#8221;), there are no property management contracts, real property service contracts, construction contracts, reciprocal easement agreements, or any other contracts related
    to the leasing, subleasing, ownership, operation, maintenance, construction or development of any part of the Real Property to which Seller is a party, or, to Seller&#8217;s knowledge, to which any other Person is a party, which would be binding on Buyer or
    otherwise will affect the Property after Closing. Seller has provided Buyer with true, correct, and complete copies (including all amendments thereto) of the Contracts. Seller is not in default under the Contracts or the other agreements disclosed in
    the Title Commitment, and, to Seller&#8217;s knowledge and except as set forth on attached <b><u>Exhibit C</u></b> or included in the Due Diligence Items made available prior to the Effective Date, no other party is in default under the Contracts or the
    other agreements disclosed in the Title Commitment, and no event has occurred which, with the giving of notice or passage of time or both, would constitute a default under the Contracts or the other agreements disclosed in the Title Commitment.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(k)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Leases</u>. Other than the Buyer-Seller Lease to be entered into at Closing, there are no Leases in effect
    granting any party the right to use or occupy any portion of the Property.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">18</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(l)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Environmental</u>. Except as set forth on attached <b><u>Exhibit C</u></b> or included in the Due
    Diligence Items made available on or prior to the Effective Date, Seller represents that Seller has not received written notice of nor is Seller actually aware of: (i) any actual or alleged violation of, or obligations or liability under, any
    applicable Environmental Laws with respect to the Property or operation at the Property; (ii) any existing, pending, anticipated, or threatened investigation of or pending, anticipated or threatened claims against Seller or the Property by any
    Governmental Entity or third party; (iii) the presence of Hazardous Materials on, under, above or emanating to or from, or having emanated to or from the Property or, to Seller&#8217;s knowledge, in the vicinity of the Property; (iv) any remedial obligations
    with respect to Seller or the Property under any Environmental Laws; (v) any Known Environmental Condition or Unknown Environmental Condition; (vi) any noncompliance, anticipated noncompliance, or threatened noncompliance of the Property or its
    operation with any Environmental Law, including any Permits or Licenses; or (vii) any Permits or Licenses required with respect to the Property or operation at the Property. Seller has delivered or otherwise made available all material and final
    reports and correspondence with Governmental Entities in Seller&#8217;s possession or control relating to the environmental condition of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(m)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Anti-Money Laundering, Anti-Terrorism and Sanctions Laws</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify; margin-left: 0.5in">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Seller is aware of, and acknowledges its obligations under, the Anti-Corruption Laws and
    Anti-Money Laundering, Anti-Terrorism and Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify; margin-left: 0.5in">(ii)&#160;&#160;&#160;&#160;&#160;&#160;At all times while this Agreement is in effect, Seller shall comply with all applicable
    Anti-Corruption, Anti-Terrorism, Anti-Money Laundering and Sanctions Laws. Without limiting the foregoing, Seller covenants that it shall not use any amounts paid pursuant to this Agreement to lend, contribute or otherwise make available such proceeds
    to any Sanctioned Person or for any use in violation of applicable Anti-Corruption, Anti-Terrorism, Anti-Money Laundering or any Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify; margin-left: 0.5in">(iii)&#160;&#160;&#160;&#160;&#160;Seller maintains, and covenants to continue to maintain during the term of this Agreement,
    compliance policies, procedures and internal controls designed to ensure compliance with applicable Anti-Corruption, Anti-Terrorism, Anti-Money Laundering and Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify; margin-left: 0.5in">(iv)&#160;&#160;&#160;&#160;&#160;Neither Seller, any Seller Control Affiliate or, to Seller&#8217;s knowledge, any Seller Significant
    Owner or Seller Representative: (i) is listed on any Government/Sanctions List; (ii) is a Sanctioned Person or otherwise the subject of any Sanctions; (iii) is or has been the subject of any investigation relating to Sanctions; (iv) has been found by a
    Sanctions Authority to have been engaged in sanctionable conduct under any Sanctions; (v) has directly or indirectly conducted, conducts or is otherwise involved with any business with or involving any sanctioned government (or any sub-division
    thereof), or any Person that is the subject of Sanctions or is located in any country that is the subject of Sanctions; (vi) directly or indirectly supports or facilitates, or plans to support or facilitate or otherwise become involved with, any such
    Person, government, entity or project; or (vii) has taken or failed to take any action that would cause it to be in non-compliance with any Anti-Corruption, Anti-Terrorism, Anti-Money Laundering or Sanctions Laws;</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">19</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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    Anti-Money Laundering, or Sanctions Laws involving Seller or any Seller Control Affiliate is pending or, to Seller&#8217;s knowledge, threatened. To Seller&#8217;s knowledge, no action, suit, investigation or proceeding relating to any Anti-Corruption,
    Anti-Terrorism, Anti-Money Laundering, or Sanctions Laws involving any Seller Significant Owner or any Seller Representative is pending or threatened;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(n)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Due Diligence Items</u>. The Due Diligence Items delivered to Buyer are in all material respects true,
    correct and complete originals or copies of the versions of the Due Diligence Items. Seller has not received written notice from any Person that any information in the Due Diligence Items is not true, accurate or complete. To Seller&#8217;s knowledge, Seller
    has delivered or made available to Buyer all of the Due Diligence Items in its possession or control that could be reasonably expected to have a material effect on the operations, use, condition, or value of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    Closing and all of the Fixtures are in good working condition and order.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(p)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tax Appeals</u>. Seller has not filed any tax certiorari or other appeals with respect to the Property
    which remain outstanding.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    negotiation period, purchase option, right of first refusal to purchase, right of first offer to purchase or similar right to purchase in connection with all or any portion of the Property (or any direct or indirect interests therein [other than with
    respect to indirect interests constituting publicly-traded securities]), except in favor of Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(r)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Defaults</u>. Seller is not in default and, to Seller&#8217;s knowledge, no other party is in default under any
    declaration or covenant recorded against title to the Property, and no event has occurred which, with the giving of notice or passage of time or both, would constitute a default thereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(s)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Warranties</u>. Attached hereto as <u>Exhibit E</u> is a true, complete, correct and complete list of all
    material warranties or guaranties issued in connection with the development, construction, operation, maintenance or repair of the Property, and all amendments and modifications thereto, which are currently in effect (collectively, the &#8220;<b>Warranties</b>&#8221;).








    True and correct copies of all of the Warranties have been delivered to Buyer. To Seller&#8217;s knowledge, the Warranties are in full force and effect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(t)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Seller Knowledge Party</u>. Seller represents and warrants that the Seller Knowledge Party is the most
    knowledgeable employee of Seller with respect to (i) the representations and warranties made by Seller under this Agreement, (ii) the Property, and (iii) the transaction contemplated by this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><b>Section 6.2&#160;&#160;&#160;Limited Liability</b>. The representations and warranties of Seller set forth in Section 6.1 of this
    Agreement will survive the Closing for a period expiring on the date that is nine (9) months after the Closing (unless Buyer has given written notice to Seller of a breach of any such representation or warranty (specifying the specific claim and
    breach) prior to the expiration of the nine (9) month period following Closing, in which event Buyer&#8217;s right to recover amounts from Seller for such noticed breach of a representation or warranty shall survive such period). Buyer will not have any
    right to bring any action against Seller as a result of any untruth or inaccuracy of such representations and warranties unless and until the aggregate amount of all liability and losses arising out of any such untruth or inaccuracy exceeds One Hundred
    Thousand and 00/100 Dollars $100,000.00 (the &#8220;<b>Basket</b>&#8221;) in which event Buyer may claim indemnification for the full amount of such claim(s) up to the Indemnification Cap (as defined below), and Seller&#8217;s liability for any untruth or inaccuracy of
    such representations and warranties shall not exceed, in the aggregate, one percent (1%) of the Purchase Price (the &#8220;<b>Indemnification Cap</b>&#8221;); it being understood and agreed, however, that such Basket and Indemnification Cap shall not apply to and
    shall expressly exclude Seller&#8217;s liabilities under Section 9.5 (Prorations and Closing Costs), Section 9.6 (Brokers) and Section 9.8 (Tax Protests; Tax Refunds and Credits). Seller shall have no liability with respect to any of Seller&#8217;s
    representations, warranties and covenants herein if, prior to the Closing, Buyer is &#8220;deemed to know&#8221; of such breach of a representation, warranty or covenant of Seller herein and Buyer nevertheless consummates the transaction contemplated by this
    Agreement. Buyer shall be &#8220;deemed to know&#8221; of such a breach if: (i) it is disclosed in this Agreement or any Exhibit or Schedule hereto; (ii) it is disclosed in the Due Diligence Items or other information that is in the Data Room not less than two (2)
    business days before the Closing; (iii) it is disclosed in any written reports obtained by Buyer before the Closing; or (iv) it is within the actual knowledge of the Buyer Designated Person (as hereinafter defined) before the Closing. The provisions of
    this Section 6.2 shall survive the Closing or any earlier termination of this Agreement and delivery of the Deed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"></p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">20</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><b>Section 6.3&#160;&#160;&#160;&#160;&#160;Knowledge Parties.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If a representation, warranty or other statement is made in this Agreement or in any document or instrument
    to be delivered at Closing pursuant to this Agreement, on the basis of the &#8220;knowledge,&#8221; &#8220;actual knowledge&#8221; or &#8220;best of knowledge&#8221; (or similar phrases) of Seller then such representation, warranty or other statement is made based on the actual, current,
    conscious express awareness of facts or other information of Elizabeth L. Hougen (&#8220;<b>Seller Knowledge Party</b>&#8221;), as distinguished from implied, imputed and/or constructive knowledge, as of the Effective Date, and without undertaking any special
    inquiry or investigation by such person(s). Seller is not under a duty of inquiry or investigation in order to make any such representation, warranty, or other statement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If a representation, warranty or other statement is made in this Agreement or in any document or instrument
    to be delivered at Closing pursuant to this Agreement, on the basis of the &#8220;knowledge,&#8221; &#8220;actual knowledge&#8221; or &#8220;best of knowledge&#8221; (or similar phrases) of Buyer then such representation, warranty or other statement is made based on the actual, current,
    conscious express awareness of facts or other information of Tycho Suter (&#8220;<b>Buyer Designated Person</b>&#8221;), as distinguished from implied, imputed and/or constructive knowledge, as of the Effective Date and as of any time thereafter up to and
    including the Closing, and without undertaking any special inquiry or investigation by such person(s). Buyer represents and warrants to Seller that such individuals are the persons most knowledgeable in connection with the representations and
    warranties made by Buyer under this Agreement. Buyer is not under a duty of inquiry or investigation in order to make any such representation, warranty, or other statement.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">21</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 6.4 &#160;&#160;&#160;&#160;Liability of Representations and Warranties</b>. The parties acknowledge that the individuals named above
    are named solely for the purpose of defining and narrowing the scope of Seller&#8217;s and Buyer&#8217;s knowledge, as applicable, and not for the purpose of imposing any liability on or creating any duties running from such individuals to the counterparty under
    this Agreement, as applicable. Each of Seller and Buyer covenants that it will bring no action of any kind against such individuals, as applicable, or related to or arising out of these representations and warranties.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE VII</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">REPRESENTATIONS AND WARRANTIES OF BUYER</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><b>Section 7.1&#160;&#160;&#160;&#160;&#160;Buyer&#8217;s Representations and Warranties</b>. Buyer represents and warrants to Seller the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Status</u>. Buyer is a limited liability company duly organized or formed, validly existing and in good
    standing under the laws of the State of Delaware and is qualified to transact business in the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Authority</u>. The execution and delivery of this Agreement and the performance of Buyer&#8217;s obligations
    hereunder have been or will be duly authorized by all necessary action on the part of Buyer and this Agreement constitutes the legal, valid, and binding obligation of Buyer, subject to equitable principles and principles governing creditors&#8217; rights
    generally.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Contravention</u>. The execution and delivery of this Agreement by Buyer and the consummation by Buyer
    of the transactions contemplated hereby will not violate any judgment, order, injunction, decree, regulation or ruling of any court or Governmental Entity or conflict with, result in a breach of, or constitute a default under the organizational
    documents (including any amendments thereto) of Buyer, any note or other evidence of indebtedness, any mortgage, deed of trust or indenture, or any lease or other material agreement or instrument to which Buyer is a party or by which it is bound.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Consents</u>. No consent, waiver, approval, or authorization is required from any Person (that has not
    already been obtained or, in the case of authorization by Buyer and its direct and indirect members, will be obtained prior to the Closing) in connection with the execution and delivery of this Agreement by Buyer or the performance by Buyer of the
    transactions contemplated hereby.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Bankruptcy</u>. Buyer has not (i) commenced a voluntary case, or had entered against it a petition, for
    relief under any federal bankruptcy act or any similar petition, order or decree under any federal or state law or statute relative to bankruptcy, insolvency or other relief for debtors, (ii) caused, suffered or consented to the appointment of a
    receiver, trustee, administrator, conservator, liquidator or similar official in any federal, state or foreign judicial or non-judicial proceeding, to hold, administer and/or liquidate all or substantially all of its property, or (iii) made an
    assignment for the benefit of creditors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Patriot Act</u>. Buyer is in compliance with all applicable anti-money laundering and anti-terrorist laws,
    regulations, rules, executive orders and government guidance, including the reporting, record keeping and compliance requirements of the Bank Secrecy Act, as amended by The International Money Laundering Abatement and Financial Anti-Terrorism Act of
    2001, Title III of the Patriot Act, and other authorizing statutes, executive orders and regulations administered by OFAC, and related Securities and Exchange Commission, SRO or other agency rules and regulations, and has policies, procedures, internal
    controls and systems that are reasonably designed to ensure such compliance. </p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">22</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>OFAC</u>. None of: (i) Buyer, any direct Affiliate of Buyer nor any Person controlled by Buyer; nor (ii)
    any Person who owns a controlling interest in or otherwise controls Buyer; nor (iii) to the best of knowledge of Buyer, after making due inquiry, if Buyer is a privately held entity, any Person otherwise having a direct or indirect beneficial interest
    (other than with respect to an interest in a publicly traded entity or beneficiaries of a pension plan that holds indirect interests in Buyer) in Buyer; nor (iv) any Person for whom Buyer is acting as agent or nominee in connection with this
    investment, is a country, territory, Person, organization, or entity named on an OFAC List, nor is a prohibited country, territory, Person, organization, or entity under any economic sanctions program administered or maintained by OFAC.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE VIII</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">OPERATING COVENANTS</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.1 Buyer-Seller Lease</b>. The parties acknowledge and agree that, pursuant and subject to the terms of the
    Buyer-Seller Lease, Seller, as tenant thereunder, shall occupy the Property from and after Closing without interruption. Seller shall have no obligation to remove any personal property or otherwise vacate or discontinue use of the Property upon or
    after Closing, or to make repairs or improvements to the Property before, upon or following Closing, except as expressly provided in this Agreement or in the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.2 Warranty Transfer</b>. With respect to any Warranties in effect on the Closing Date, Seller shall: (i)
    deliver written notice to any party (&#8220;<b>Warrantor</b>&#8221;) that is liable for each Warranty that is being assigned to Buyer pursuant to this Agreement that such Warranty is being assigned, (ii) use commercially reasonable efforts to cause the Warrantor
    to deliver to Seller all forms and other requirements for the assignment of the Warranty, if any (&#8220;<b>Warranty Assignment Package</b>&#8221;), and (iii) execute the necessary documents in the Warranty Assignment Package and take any other actions that are
    reasonably necessary to assign the respective Warranty in accordance with the procedures of the respective Warrantor. To the extent that any Warranty is not transferred to Buyer at the Closing as aforesaid, such failure shall not be deemed a default by
    Seller of this Agreement or otherwise entitle Buyer to terminate this Agreement, but Seller shall continue to use commercially reasonable efforts following the Closing to take actions reasonably necessary to assign the respective Warranty to Buyer and
    shall enforce any such Warranty on Buyer&#8217;s behalf at the direction of Buyer. This Section 8.2 shall survive the Closing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE IX</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">CLOSING</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.1 Escrow Instructions</b>. Upon execution of this Agreement, the parties hereto shall deposit an executed
    counterpart of this Agreement with the Escrow Holder, and this Agreement shall serve as escrow instructions to the Escrow Holder as the escrow holder for consummation of the purchase and sale contemplated hereby. Seller and Buyer agree to execute such
    reasonable additional and supplementary escrow instructions as may be appropriate to enable the Escrow Holder to comply with the terms of this Agreement; provided, however, that in the event of any conflict between the provisions of this Agreement and
    any supplementary escrow instructions, the terms of this Agreement shall control.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">23</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.2 Closing</b>. The closing hereunder (&#8220;<b>Closing</b>&#8221; or &#8220;<b>Close of Escrow</b>&#8221;) shall be held and delivery
    of all items to be made at the Closing under the terms of this Agreement shall be made through escrow at Escrow Holder&#8217;s office on the Closing Date. Prior to the Effective Date, Buyer requested that the Escrow Holder prepare and deliver to Buyer and
    Seller a preliminary closing statement (the &#8220;<b>Closing Statement</b>&#8221;). On the Closing Date, Buyer shall deposit in escrow with the Escrow Holder the Purchase Price (subject to adjustments described in Section 9.5), together with all other costs and
    amounts to be paid by Buyer at the Closing pursuant to the terms of this Agreement, by Federal Reserve wire transfer of immediately available funds to an account to be designated by the Escrow Holder. No later than 11:00 a.m. Pacific Time on the
    Closing Date and provided all conditions to Closing set forth in Section 9.2 have been satisfied, or waived or deemed waived by Buyer, (A) Buyer and Seller will authorize the Escrow Holder to (i) pay to Seller by Federal Reserve wire transfer of
    immediately available funds to an account designated by Seller, the Purchase Price (subject to adjustments described in Section 9.5, less any costs or other amounts to be paid by Seller at Closing pursuant to the terms of this Agreement and the Closing
    Statement, and (ii) pay all appropriate payees the other costs and amounts to be paid by Buyer at Closing pursuant to the terms of this Agreement, and (iii) record the Deed and distribute fully-executed copies of all Closing Documents to each of Buyer
    and Seller, and (B) to otherwise pay to the appropriate payees out of the proceeds of Closing payable to Seller all costs and amounts to be paid by Seller at Closing pursuant to the terms of this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.3 Seller&#8217;s Closing Documents and Other Items</b>. At or before Closing, Seller shall deposit into escrow the
    following items:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a duly executed and acknowledged Grant Deed in the form of attached <b><u>Exhibit F</u></b> (the &#8220;<b>Deed</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;two (2) duly executed counterparts of the Buyer-Seller Lease, one (1) duly executed and acknowledged
    counterpart of a memorandum of the Buyer-Seller Lease and at least one (1) original of any other agreements, documents or instruments contemplated by the Buyer-Seller Lease to be executed and delivered by Seller, as tenant, in connection therewith;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;an executed California Form 593 Real Estate Withholding Certificate;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;two (2) duly executed counterparts of a Bill of Sale and Assignment and Assumption Agreement in the form of
    attached <b><u>Exhibit H</u></b> (the &#8220;<b>Assignment</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;an affidavit pursuant to Section 1445(b)(2) of the Code, on which Buyer is entitled to rely, that Seller (or,
    if Seller is a disregarded entity for federal income tax purposes, the person treated as the owner of the Property for such purposes) is not a &#8220;foreign person&#8221; within the meaning of Section 1445(f)(3) of the Code in the form attached as <b><u>Exhibit
        L</u></b> (&#8220;<b>FIRPTA Certificate</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;documentation to establish to the Title Company&#8217;s satisfaction the due authority of Seller&#8217;s disposition of
    the Property and Seller&#8217;s delivery of the documents required to be delivered by Seller pursuant to this Agreement (including, but not limited to, the organizational documents of Seller, as they may have been amended from time to time, resolutions of
    Seller and incumbency certificates of Seller);</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;any consents then-obtained by Seller in order to transfer the Warranties to Buyer, subject to Section 8.2
    above;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(j)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;such other documents as may be reasonably required by the Title Company or as may be agreed upon by Seller
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;two (2) duly executed counterparts of the Buyer-Seller Lease, one (1) duly executed and acknowledged
    counterpart of a memorandum of the Buyer-Seller Lease and at least one (1) original of any other agreements, documents or instruments contemplated by the Buyer-Seller Lease to be executed and delivered by Buyer, as landlord, in connection therewith;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;documentation to establish to Title Company&#8217;s reasonable satisfaction the due authority of Buyer&#8217;s acquisition
    of the Property and Buyer&#8217;s delivery of the documents required to be delivered by Buyer pursuant to this Agreement (including, but not limited to, the organizational documents of Buyer, as they may have been amended from time to time, resolutions of
    Buyer and incumbency certificates of Buyer);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a counterpart signature to the Closing Statement executed by Buyer;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a duly completed and signed Preliminary Change of Ownership Report (pursuant to California Revenue &amp;
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;such other documents as may be reasonably required by the Title Company or as may be agreed upon by Seller and
    Buyer to consummate the purchase of the Property as contemplated by this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><b>Section 9.5&#160;&#160;&#160;Prorations and Closing Costs.</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Real estate and personal property taxes, utilities and all other proratable items shall remain the
    responsibility of Seller pursuant to the Buyer-Seller Lease and all payments of the same that may be due and payable as of Closing shall remain Seller&#8217;s responsibility; provided, however, that solely for accounting purposes, all such proratable items
    paid by Seller upon Closing but attributable to amounts accruing on and after of 12:01 a.m. Pacific Time on the Closing Date shall be credited to Seller&#8217;s obligation to pay such expenses as the &#8220;tenant&#8221; under the Buyer-Seller Lease.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">25</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Seller shall pay (a) one-half (1/2) of Escrow Holder&#8217;s escrow fee, (b) the document-drafting and recording
    charges for the Deed, (c) all city and county documentary transfer taxes required by law, (d) the costs for all title insurance search fees and commitment fees, and all premiums for the Title Policy and costs of any curative endorsements to remove
    certain disapproved title matters thereto, and (e) the cost of any Seller&#8217;s Required Removal Items. Buyer shall pay (i) one-half (1/2) of Escrow Holder&#8217;s escrow fee, (ii) all document-drafting and recording charges for any loan documents for Buyer,
    (iii) the cost of all third party studies and reports obtained by Buyer in connection with Buyer&#8217;s inspections and investigation, (iv) the cost for any Title Policy endorsements requested by Buyer, and (v) any other costs customarily charged Buyers in
    the City of Carlsbad. All other closing costs shall be allocated as is customary in the City of Carlsbad. Except as expressly set forth otherwise in this Agreement, each Party shall pay its own legal fees.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.6 Brokers</b>. Buyer and Seller covenant and represent to each other that, to their knowledge, there is no
    party entitled to a real estate commission, finder&#8217;s fee, cooperation fee, or other brokerage-type fee or similar compensation in connection with this Agreement and the transactions contemplated hereby other than CBRE, Inc. Each party agrees to defend,
    indemnify, and hold the other party, its employees, representatives and agents safe and harmless from and against any and all such Claims from any other broker, agent, individual or entity claiming by or though the indemnifying party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.7 Expenses</b>. Except as provided in Section 9.5 and Section 9.6, each party hereto shall pay its own expenses
    incurred in connection with this Agreement and the transactions contemplated hereby, including, without limitation in the case of Buyer, all third-party engineering and environmental review costs and all other due diligence costs.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.8 Tax Protests; Tax Refunds and Credits</b>. Seller shall have the right to control the progress of and to make
    all decisions with respect to any contest of the real estate taxes and personal property taxes for the Real Property due and payable during all tax years through and including the tax year in which the Closing occurs (the &#8220;<b>Closing Tax Year</b>&#8221;);
    provided Seller shall keep Buyer fully informed regarding the status of any contest with respect to the taxes attributable to such period. To the extent any real estate or personal property tax refunds or credits are received after Closing with respect
    to the Property and such refunds or credits are attributable to real estate and personal property taxes paid for any tax year prior to and including the Closing Tax Year, Seller shall be entitled to the entirety of such refunds and credits. Any contest
    of the real estate taxes and personal property taxes for the Property due and payable for all years subsequent to the Closing Tax Year, and any real estate or personal property tax refunds or credits attributable to such period, shall be governed by
    the terms of the Buyer-Seller Lease.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">26</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE X</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">MISCELLANEOUS</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<b>Amendment and Modification</b>. Subject to applicable law, this Agreement may be amended, modified, or
    supplemented only by a written agreement signed by the party against whom enforcement is sought.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<b>Notices</b>. All notices required or permitted hereunder shall be in writing and shall be served on the
    parties at the following address(es):</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; width: 100%; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: bottom">
        <td style="width: 44%; text-align: right; vertical-align: top">If to Seller:</td>
        <td style="width: 2%">&#160;</td>
        <td style="width: 54%; text-align: justify">
          <p style="margin-top: 0; margin-bottom: 0">Ionis Pharmaceuticals, Inc.</p>
          <p style="margin-top: 0; margin-bottom: 0">2855 Gazelle Ct. <br>
            Attention: General Counsel <br>
            Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">with a copy to:</td>
        <td>&#160;</td>
        <td style="text-align: justify">
          <p style="margin-top: 0; margin-bottom: 0">Cooley LLP <br>
            4401 Eastgate Mall</p>
          <p style="margin-top: 0; margin-bottom: 0">San Diego, CA 92121 <br>
            Attention: David Crawford</p>
          <p style="margin-top: 0; margin-bottom: 0">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">If to Buyer:</td>
        <td>&#160;</td>
        <td style="text-align: justify">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">c/o Oxford Properties Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Boston, MA 02110</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Attn: Kristen Binck</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">With a copy to:</td>
        <td>&#160;</td>
        <td style="text-align: justify">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">c/o Oxford Properties Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">450 Park Avenue, 9<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">New York, NY 10022</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Attn: Legal Department</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Email:</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">[***]</p>
        </td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">With a copy to:</td>
        <td>&#160;</td>
        <td style="text-align: justify">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">DLA Piper LLP (US)</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">33 Arch Street, 26<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Boston, MA 02110</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Attn: John L. Sullivan, Esq.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="text-align: right; vertical-align: top">If to Escrow <br>
          Holder:</td>
        <td>&#160;</td>
        <td style="text-align: justify">
          <p style="margin-top: 0; margin-bottom: 0">First American Title Insurance Company</p>
          <p style="margin-top: 0; margin-bottom: 0">4380 La Jolla Drive <br>
            Suite 110 <br>
            San Diego, CA 92122 <br>
            Attn: [***]</p>
        </td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Any such notices may be sent by (a) certified mail, return receipt requested, in which case notice shall be deemed delivered upon actual or
    attempted but refused delivery, (b) a nationally recognized overnight courier, in which case notice shall be deemed delivered upon actual or attempted but refused delivery, (c) personal delivery, in which case notice shall be deemed delivered upon
    actual or attempted but refused delivery, or (d) Email transmission. The above addresses and Email addresses may be changed by written notice to the other party; provided that no notice of a change of address or Email address shall be effective until
    actual receipt of such notice.</p>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; text-align: justify" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">27</font></div>
    <div style="page-break-after: always; text-align: justify" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.2 Successors and Assigns</b>. This Agreement will be binding upon and inure to the benefit of Seller and Buyer
    and their respective successors and assigns, and no other party will be conferred any rights by virtue of this Agreement or be entitled to enforce any of the provisions hereof. Whenever a reference is made in this Agreement to Seller or Buyer, such
    reference will include the successors and permitted assigns of such party under this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">Section 10.3 Governing Law and Consent to Jurisdiction<font style="font-weight: normal">.</font> THIS AGREEMENT SHALL
    BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF CALIFORNIA, WITHOUT REGARD TO ANY OTHERWISE APPLICABLE PRINCIPLES OF CONFLICTS OF LAWS. ANY ACTION ARISING OUT OF THIS AGREEMENT MUST BE COMMENCED BY BUYER OR SELLER IN THE
    STATE COURTS OF THE STATE OF CALIFORNIA OR IN U.S. FEDERAL COURTS HAVING JURISDICTION OVER THE STATE OF CALIFORNIA AND EACH PARTY HEREBY CONSENTS TO THE JURISDICTION OF THE ABOVE COURTS IN ANY SUCH ACTION AND TO THE LAYING OF VENUE IN THE STATE OF
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.4 Counterparts; Electronic Signatures</b>. This Agreement may be executed in counterparts, each of which shall
    be deemed an original, but such counterparts, when taken together, shall constitute one agreement. This Agreement may be executed by a Party&#8217;s signature transmitted by email, and copies of this Agreement executed and delivered by means of emailed
    signatures shall have the same force and effect as copies hereof executed and delivered with original signatures. All parties hereto may rely upon emailed signatures (including signatures in Portable Document Format) as if such signatures were
    originals. All parties hereto agree that an emailed signature page may be introduced into evidence in any proceeding arising out of or related to this Agreement as if it were an original signature page.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    agreements executed by Buyer and/or its Affiliates, investors, and other related parties with respect to the transactions contemplated by this Agreement) to be furnished pursuant to the provisions hereof embody the entire agreement and understanding of
    the parties hereto as to the subject matter contained herein. There are no restrictions, promises, representations, warranties, covenants, or undertakings other than those expressly set forth or referred to in such documents. This Agreement and such
    documents (including, without limitation, non-disclosure agreements executed by Buyer and/or its Affiliates, investors, and other related parties with respect to the transactions contemplated by this Agreement) supersede all prior agreements and
    understandings among the parties with respect to the subject matter hereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.6 Severability</b>. Any term or provision of this Agreement that is invalid or unenforceable in any
    jurisdiction will, as to such jurisdiction, be ineffective to the extent of such invalidity or unenforceability without rendering invalid or unenforceable the remaining terms and provisions of this Agreement or affecting the validity or enforceability
    of any of the terms or provisions of this Agreement.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.7 Attorney Fees</b>. If any action is brought by any party to this Agreement to enforce or interpret its terms
    or provisions, the prevailing party (whether by final judgment or out of court settlement) will be entitled to reasonable out of pocket third-party attorney fees and costs and expenses of suit incurred in connection with such action prior to and at
    trial and on any appeal therefrom. Any judgment or order entered in any final judgment shall contain a specific provision providing for the recovery of all costs and expenses of suit, including reasonable out of pocket third-party attorneys&#8217; fees
    (collectively &#8220;<b>Costs</b>&#8221;) incurred in enforcing, perfecting and executing such judgment. For the purposes of this paragraph, Costs shall include, without limitation, reasonable out of pocket third-party attorneys&#8217; fees, costs and expenses incurred
    in (i) post-judgment motions, (ii) contempt proceeding, (iii) garnishment, levy, and debtor and third party examination, (iv) discovery, and (v) bankruptcy litigation.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    its own fees and expenses, including those of its counsel and accountants, incurred in the negotiation, preparation, and consummation of this Agreement and the transaction contemplated hereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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    between Buyer and Seller.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.10 <u>JUDICIAL REFERENCE</u></b>. IT IS THE DESIRE AND INTENTION OF THE PARTIES TO AGREE UPON A MECHANISM AND
    PROCEDURE UNDER WHICH CONTROVERSIES AND DISPUTES ARISING OUT OF THE AGREEMENT, AS AMENDED, OR RELATED TO THE PROPERTY WILL BE RESOLVED IN A PROMPT AND EXPEDITIOUS MANNER. ACCORDINGLY, ANY ACTION, PROCEEDING OR COUNTERCLAIM BROUGHT BY EITHER PARTY
    HERETO AGAINST THE OTHER (AND/OR AGAINST ITS OFFICERS, DIRECTORS, EMPLOYEES, AGENTS OR SUBSIDIARIES OR AFFILIATED ENTITIES) ON ANY MATTERS WHATSOEVER ARISING OUT OF OR IN ANY WAY CONNECTED WITH THIS AGREEMENT, AS AMENDED, ANY CLAIM OF INJURY OR DAMAGE,
    WHETHER SOUNDING IN CONTRACT, TORT, OR OTHERWISE, SHALL BE HEARD AND RESOLVED BY A REFEREE UNDER THE PROVISIONS OF THE CALIFORNIA CODE OF CIVIL PROCEDURE, SECTIONS 638 &#8212; 645.1, INCLUSIVE (AS SAME MAY BE AMENDED, OR ANY SUCCESSOR STATUTE(S) THERETO)
    (THE &#8220;<b>REFEREE SECTIONS</b>&#8221;). ANY FEE TO INITIATE THE JUDICIAL REFERENCE PROCEEDINGS AND ALL FEES CHARGED AND COSTS INCURRED BY THE REFEREE SHALL BE PAID BY THE PARTY INITIATING SUCH PROCEDURE (EXCEPT THAT IF A REPORTER IS REQUESTED BY EITHER PARTY,
    THEN A REPORTER SHALL BE PRESENT AT ALL PROCEEDINGS WHERE REQUESTED AND THE FEES OF SUCH REPORTER &#8211; EXCEPT FOR COPIES ORDERED BY THE OTHER PARTIES &#8211; SHALL BE BORNE BY THE PARTY REQUESTING THE REPORTER); PROVIDED HOWEVER, THAT ALLOCATION OF THE COSTS
    AND FEES, INCLUDING ANY INITIATION FEE, OF SUCH PROCEEDING SHALL BE ULTIMATELY DETERMINED IN ACCORDANCE WITH THIS SECTION. THE VENUE OF THE PROCEEDINGS SHALL BE IN THE COUNTY IN WHICH THE PROPERTY IS LOCATED. WITHIN TEN (10) DAYS OF RECEIPT BY ANY
    PARTY OF A WRITTEN REQUEST TO RESOLVE ANY DISPUTE OR CONTROVERSY PURSUANT TO THIS SECTION 10, THE PARTIES SHALL AGREE UPON A SINGLE REFEREE WHO SHALL TRY ALL ISSUES, WHETHER OF FACT OR LAW, AND REPORT A FINDING AND JUDGMENT ON SUCH ISSUES AS REQUIRED
    BY THE REFEREE SECTIONS. IF THE PARTIES ARE UNABLE TO AGREE UPON A REFEREE WITHIN SUCH TEN (10) DAY PERIOD, THEN ANY PARTY MAY THEREAFTER FILE A LAWSUIT IN THE COUNTY IN WHICH THE PROPERTY IS LOCATED FOR THE PURPOSE OF APPOINTMENT OF A REFEREE UNDER
    THE REFEREE SECTIONS. IF THE REFEREE IS APPOINTED BY THE COURT, THE REFEREE SHALL BE A NEUTRAL AND IMPARTIAL RETIRED JUDGE WITH SUBSTANTIAL EXPERIENCE IN THE RELEVANT MATTERS TO BE DETERMINED, FROM JAMS, THE AMERICAN ARBITRATION ASSOCIATION OR SIMILAR
    MEDIATION/ARBITRATION ENTITY. THE PROPOSED REFEREE MAY BE CHALLENGED BY ANY PARTY FOR ANY OF THE GROUNDS LISTED IN THE REFEREE SECTIONS. THE REFEREE SHALL HAVE THE POWER TO DECIDE ALL ISSUES OF FACT AND LAW AND REPORT HIS OR HER DECISION ON SUCH
    ISSUES, AND TO ISSUE ALL RECOGNIZED REMEDIES AVAILABLE AT LAW OR IN EQUITY FOR ANY CAUSE OF ACTION THAT IS BEFORE THE REFEREE, INCLUDING AN AWARD OF ATTORNEYS&#8217; FEES AND COSTS IN ACCORDANCE WITH THIS AGREEMENT, AS AMENDED. THE REFEREE SHALL NOT,
    HOWEVER, HAVE THE POWER TO AWARD PUNITIVE DAMAGES, NOR ANY OTHER DAMAGES WHICH ARE NOT PERMITTED BY THE EXPRESS PROVISIONS OF THE AGREEMENT, AS AMENDED, AND THE PARTIES HEREBY WAIVE ANY RIGHT TO RECOVER ANY SUCH DAMAGES. THE PARTIES SHALL BE ENTITLED
    TO CONDUCT ALL DISCOVERY AS PROVIDED IN THE CALIFORNIA CODE OF CIVIL PROCEDURE, AND THE REFEREE SHALL OVERSEE DISCOVERY AND MAY ENFORCE ALL DISCOVERY ORDERS IN THE SAME MANNER AS ANY TRIAL COURT JUDGE, WITH RIGHTS TO REGULATE DISCOVERY AND TO ISSUE AND
    ENFORCE SUBPOENAS, PROTECTIVE ORDERS AND OTHER LIMITATIONS ON DISCOVERY AVAILABLE UNDER CALIFORNIA LAW. THE REFERENCE PROCEEDING SHALL BE CONDUCTED IN ACCORDANCE WITH CALIFORNIA LAW (INCLUDING THE RULES OF EVIDENCE), AND IN ALL REGARDS, THE REFEREE
    SHALL FOLLOW CALIFORNIA LAW APPLICABLE AT THE TIME OF THE REFERENCE PROCEEDING. THE PARTIES SHALL PROMPTLY AND DILIGENTLY COOPERATE WITH ONE ANOTHER AND THE REFEREE AND SHALL PERFORM SUCH ACTS AS MAY BE NECESSARY TO OBTAIN A PROMPT AND EXPEDITIOUS
    RESOLUTION OF THE DISPUTE OR CONTROVERSY IN ACCORDANCE WITH THE TERMS OF THIS SECTION. IN THIS REGARD, THE PARTIES AGREE THAT THE PARTIES AND THE REFEREE SHALL USE BEST EFFORTS TO ENSURE THAT (A) DISCOVERY BE CONDUCTED FOR A PERIOD NO LONGER THAN SIX
    (6) MONTHS FROM THE DATE THE REFEREE IS APPOINTED, EXCLUDING MOTIONS REGARDING DISCOVERY, AND (B) A TRIAL DATE BE SET WITHIN NINE (9) MONTHS OF THE DATE THE REFEREE IS APPOINTED. IN ACCORDANCE WITH SECTION 644 OF THE CALIFORNIA CODE OF CIVIL PROCEDURE,
    THE DECISION OF THE REFEREE UPON THE WHOLE ISSUE MUST STAND AS THE DECISION OF THE COURT, AND UPON THE FILING OF THE STATEMENT OF DECISION WITH THE CLERK OF THE COURT, OR WITH THE JUDGE IF THERE IS NO CLERK, JUDGMENT MAY BE ENTERED THEREON IN THE SAME
    MANNER AS IF THE ACTION HAD BEEN TRIED BY THE COURT. ANY DECISION OF THE REFEREE AND/OR JUDGMENT OR OTHER ORDER ENTERED THEREON SHALL BE APPEALABLE TO THE SAME EXTENT AND IN THE SAME MANNER THAT SUCH DECISION, JUDGMENT, OR ORDER WOULD BE APPEALABLE IF
    RENDERED BY A JUDGE OF THE SUPERIOR COURT IN WHICH VENUE IS PROPER HEREUNDER. THE REFEREE SHALL IN HIS/HER STATEMENT OF DECISION SET FORTH HIS/HER FINDINGS OF FACT AND CONCLUSIONS OF LAW. THE PARTIES INTEND THIS GENERAL REFERENCE AGREEMENT TO BE
    SPECIFICALLY ENFORCEABLE IN ACCORDANCE WITH THE CODE OF CIVIL PROCEDURE. NOTHING IN THIS SECTION SHALL PREJUDICE THE RIGHT OF ANY PARTY TO OBTAIN PROVISIONAL RELIEF OR OTHER EQUITABLE REMEDIES FROM A COURT OF COMPETENT JURISDICTION AS SHALL OTHERWISE
    BE AVAILABLE UNDER THE CODE OF CIVIL PROCEDURE AND/OR APPLICABLE COURT RULES.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
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    hereunder shall fall on a day that is not a Business Day, the deadline for such performance shall be deemed to be the next Business Day following such day.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.12 No Waiver</b>. No waiver of any of the provisions of this Agreement shall be deemed, or shall constitute, a
    waiver of any other provision, whether or not similar, nor shall any waiver constitute a continuing waiver, nor shall a waiver in any instance constitute a waiver in any subsequent instance. No waiver shall be binding unless executed in writing by the
    Party making the waiver.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.14 No Third Party Beneficiaries</b>. Nothing in this Agreement is intended to benefit any third party, or
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.15 Exculpation</b>. Except as expressly set forth in this Agreement or in the Joinder by Seller Parent
    attached hereto, (a) Seller&#8217;s shareholders, partners, members, the partners or members of such partners or members, the shareholders of such partners or members, and the trustees, officers, directors, employees, agents and security holders of Seller
    and the partners or members of Seller assume no personal liability for any obligations entered into on behalf of Seller and its individual assets shall not be subject to any claims of any person relating to such obligations, (b) Buyer&#8217;s shareholders,
    partners, members, the partners or members of such partners or members, the shareholders of such partners or members, and the trustees, officers, directors, employees, agents and security holders of Buyer and the partners or members of Buyer assume no
    personal liability for any obligations entered into on behalf of Buyer and their individual assets shall not be subject to any claims of any person relating to such obligations. The foregoing shall govern any direct and indirect obligations of Seller
    under this Agreement. The provisions of this Section 10.16 shall survive the Closing or any termination of this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly executed as of the day and year first above
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        <td style="text-align: left"><b>&#160;</b></td>
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        <td colspan="4" style="text-align: left"><b>IONIS GAZELLE, LLC</b>, a Delaware limited liability company</td>
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        <td style="text-align: left">&#160;</td>
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        <td style="text-align: left">&#160;</td>
        <td style="text-align: left">&#160;</td>
        <td style="text-align: left">&#160;</td>
        <td style="text-align: left">&#160;</td>
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        <td style="text-align: left"><b>&#160;</b></td>
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        <td style="text-align: left">&#160;</td>
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        <td style="text-align: left">&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">[<i>Signature Page - Oxford Ionis Campus Purchase and Sale Agreement</i>]</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><i>&#160;</i></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>JOINDER BY ESCROW HOLDER:</b><i>&#160;</i></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">The Escrow Holder is executing this Agreement to evidence its agreement to act as escrow agent in accordance with the terms
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        <td style="font-weight: bold">&#160;</td>
        <td style="font-weight: bold">&#160;</td>
        <td style="font-weight: bold">&#160;</td>
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        <td style="font-weight: bold; width: 2%">&#160;</td>
        <td style="font-weight: bold; width: 1%">&#160;</td>
        <td style="font-weight: bold; width: 2%">&#160;</td>
        <td style="font-weight: bold; width: 45%">&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>JOINDER BY SELLER PARENT</b></p>
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    defense available to a surety under applicable law. In the event of any failure on the part of Seller to fulfill the Obligations, a separate action or actions may be brought and prosecuted against Seller Parent whether or not Seller is joined therein
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    by Seller Parent, or otherwise concerning this Joinder by Seller Parent or the transactions contemplated hereby, the prevailing party (regardless of whether such party prevails on substantive or procedural grounds) shall be entitled to recover from the
    other party all costs and expenses of any such action, including, but not limited to, attorneys&#8217; fees and expenses, including all such costs and expenses incurred in any trial, on any appeal, in any bankruptcy proceeding (including the adjudication of
    issues peculiar to bankruptcy law) and in any petition for review. Each party also shall have the right to recover its costs and attorneys&#8217; fees incurred in collecting any sum or debt owed to it by the other party, with or without litigation, if such
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">[<i>Joinder &#8211; Parent &#8211; Oxford Ionis Campus Purchase and Sale Agreement</i>]</p>
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    ARISING OUT OF OR RELATING TO THIS JOINDER BY SELLER PARENT. THIS WAIVER IS A MATERIAL INDUCEMENT FOR SELLER PARENT AND BUYER TO ENTER INTO AND ACCEPT THIS JOINDER BY SELLER PARENT. Any action brought hereunder shall be brought in a court of law
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  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; width: 100%; font: 10pt Times New Roman, Times, Serif">

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        <td>&#160;</td>
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        <td>&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>SCHEDULE 3.2(B)</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">Oxford Properties Expands its San Diego Life Science Presence with Purchase and Lease Back of Ionis Campus</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">The transaction follows on from Oxford&#8217;s entrance into the San Diego life science market in February this year via a US$464 million acquisition
    of a 13-building portfolio. It builds on Oxford&#8217;s already robust global life sciences portfolio and growing West Coast presence with high quality assets in the Bay Area and Seattle. The acquisition grows Oxford&#8217;s existing San Diego life science
    portfolio to 900,000 square feet of income-producing properties, which will increase to over 1.2 million square feet upon completion of its development pipeline in the local market.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Founded in 1989, Ionis is a publicly traded biotech company and a leader in discovering and developing RNA-targeted therapeutics. Ionis
    currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. It has a long history of R&amp;D successes and has delivered multiple breakthroughs in antisense
    technology.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#8220;Our team continues to create sustained yet highly-targeted growth against one of our highest conviction global investment strategies, to build
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    growing portfolio plus complements our development pipeline in San Diego. The transaction perfectly encapsulates the purpose of our life science business; by investing Oxford&#8217;s capital and capabilities to own, build and manage this highly technical
    real estate infrastructure we are able to free up the resources of life science firms to better focus on what they do best &#8211; research and create the life changing therapeutics of tomorrow. We look forward to working with Ionis as they continue to
    advance their science for the benefit of society at large.&#8221;</p>
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    near-term capital needs to scale our organization to deliver on our growth initiatives. This transaction will provide us with significant cash proceeds while allowing us to conduct our day-to-day operations as we normally do. We have worked closely
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    are all modern vintage, with the oldest completed in 2011 and the most recent in 2021. They feature chemistry labs, biology labs and R&amp;D support systems as well as modern office space. The campus is located in Carlsbad, part of the prominent San
    Diego North County life science cluster and home to leading firms such as Novartis, Thermo Fisher and Genentech. The North County has become highly sought after by life science firms in recent years, which has dropped the vacancy rate to 3.6%<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup>.</p>
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    or higher, rapidly outpacing the national average of 28%, and its universities graduate more STEM talent than any other region in the US. Its ecosystem is anchored by renowned research institutions and non-profits including San Diego State University,
    UC San Diego, Scripps Research and the Sandford Burnham Prebys Medical Discovery Institute. San Diego&#8217;s life science market has witnessed record demand over recent years, leading to significant and sustained rental growth with asking rents growing by
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#8220;Our purchase of the Ionis campus adds to Oxford&#8217;s significant presence in a top three global life science market that is characterized by high
    barriers to entry,&#8221; <b>said Tycho Suter, Vice President of Investments at Oxford. </b>&#8220;We have long-term conviction in the San Diego life sciences market, which is supported by its strong STEM presence and a highly-skilled labour force as well as
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Oxford has invested in the life science industry since 2017. It has built substantial expertise in the sector while deploying capital through a
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    development opportunities. Oxford&#8217;s life science business now operates across the top 10 North American life science markets and in leading European markets through holdings in Cambridge, London and Paris.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">- Ends -</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <!-- Field: Rule-Page -->
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> From <i>Q2 2022 San Diego Life Science Marketbeat</i>, Cushman &amp; Wakefield<i>,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>About Oxford Properties Group</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Oxford Properties Group (&#8220;Oxford&#8221;) is a leading global real estate investor, asset manager and business builder. It builds, buys, and grows defined real estate
    operating business with world-class management teams. Established in 1960, Oxford and its portfolio companies manage approximately C$80 billion of assets across four continents on behalf of their investment partners. Oxford&#8217;s owned portfolio
    encompasses office, logistics, retail, multifamily residential, life sciences, hotels and credit in global gateway cities and high-growth hubs. A thematic investor with a committed source of capital, Oxford invests in properties, portfolios,
    development sites, debt, securities and real estate businesses across the risk-reward spectrum. Together with its portfolio companies, Oxford is one of the world&#8217;s most active developers with over 100 projects currently underway globally across all
    major asset classes. Oxford is owned by OMERS, the Canadian defined benefit pension plan for Ontario's municipal employees.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">For more information on Oxford, visit <u>www.oxfordproperties.com</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>Press Contact</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Daniel O&#8217;Donnell, Vice President of Communications, Oxford Properties: <u>Dodonnell@oxfordproperties.com</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Chris Sarpong, Senior Specialist, Communications, Oxford Properties: <u>csarpong@oxfordproperties.com</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -1-</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>EXHIBIT B</u></font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>List of Due Diligence Items</u></b></font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">[***]</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b><u>EXHIBIT C</u></b></font></p>
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      <b><u>Exhibit C</u></b> will be deemed to be disclosed with respect to any other section and paragraph of Article VI of the Agreement to the extent its relevance or appropriateness is reasonably apparent from the context in which it is presented and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b><u>EXHIBIT D</u></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Permitted Exceptions</u></font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">General and special taxes and assessments for the fiscal year 2022-2023, a lien not yet due or payable.</font></td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 18pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">APNs: 209-120-20-00 and 209-120-27-00</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The lien of special tax for the following community facilities district, which tax is collected with the county taxes, a
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 18pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">District: &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Carlsbad CFD #3 IMP 2</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The lien of special tax assessed pursuant to Chapter 2.5 commencing with Section 53311 of the California Government Code
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.</font></td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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      </tr>

  </table>
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        -1-</font></div>
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      </tr>

  </table>
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  </table>
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        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">An easement shown or dedicated on the map filed or recorded January 23, 2007 as Map No. 15505 of
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      </tr>

  </table>
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      </tr>

  </table>
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      </tr>

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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 17.9pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">23.</font></td>
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        -2-</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">24.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">An easement shown or dedicated on the map filed or recorded October 13, 2016 as Map No. 16145 of
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 18pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">For sight distance corridor and access roads and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">25.</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">26.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Permanent Stormwater Quality Best Management Practice Maintenance Agreement recorded April 4, 2017
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">27.</font></td>
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            Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">28.</font></td>
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            Official Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">29.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Encroachment Agreement recorded June 6, 2018 as Instrument No. 2018-0228575 of Official Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">30.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Notice of Restriction on Real Property recorded April 9, 2019 as Instrument No. 2019-0126632 of
            Official Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Landscape Maintenance Agreement recorded August 06, 2019 as Instrument No. 2019-0326652 of Official
            Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hold Harmless Agreement Drainage recorded August 06, 2019 as Instrument No. 2019-0326663 of Official
            Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">33.</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">34.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Permanent Stormwater Quality Best Management Practice Maintenance Agreement recorded August 06, 2019
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">35.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Notice of Restriction on Real Property recorded August 06, 2019 as Instrument No. 2019-0326666 of
            Official Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">36.</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">37.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hold Harmless Agreement Geological Failure recorded March 04, 2020 as Instrument No. 2020-0112317 of
            Official Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">38.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hold Harmless Agreement Drainage recorded March 04, 2020 as Instrument No. 2020-0112318 of Official
            Records.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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        -3-</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <!--PROfilePageNumberReset%Num%1%EXHIBIT E&lt;br&gt;-%-%-->
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>EXHIBIT E</u></b></font></p>
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        -1-</font></div>
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  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">[SIGNATURES ON FOLLOWING PAGE]</font></p>
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  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -1-</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>EXHIBIT J</u></b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b><u>Intentionally Omitted</u></b></font></p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT K</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b><u>Form of Title Affidavit</u></b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>STATEMENT REQUIRED FOR THE ISSUANCE OF ALTA OWNERS AND/OR LOAN
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Commitment No. NCS-1113647-SD</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Date: <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">To the best knowledge and belief of the undersigned, the following is hereby certified with
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        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That, except as noted at the end of this paragraph, within the last six (6) months (a) no labor,
            service or materials have been furnished to improve the land, or to rehabilitate, repair, refurbish, or remodel the building(s) situated on the land; (b) nor have any goods, chattels, machinery, apparatus or equipment been attached to the
            building(s) thereon, as fixtures; (c) nor have any contracts been let for the furnishing of labor, service, materials, machinery, apparatus or equipment which are to be completed subsequent to the date hereof; (d) nor have any notices of lien
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        <td style="font: 10pt Times New Roman, Times, Serif">&#160;</td>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="font: 10pt Times New Roman, Times, Serif">&#160;</td>
        <td style="font: 10pt Times New Roman, Times, Serif">&#160;</td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify">&#160;</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></p>
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        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That there are no unrecorded contracts or options to purchase the land, except the following, if
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify">&#160;</td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify">&#160;</td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify; border-bottom: Black 1pt solid">&#160;</td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="width: 20pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></td>
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        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That there are no unrecorded leases, easements or other servitudes to which the land or building, or
            portions thereof, are subject, except the following, if any:<u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </u></font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 20pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></td>
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      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That there are no unpaid real estate taxes or assessments except as shown on the current tax roll.
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 20pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></td>
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That the undersigned is authorized to execute this affidavit, has the ability to execute all
            instruments necessary to mortgage or convey the Land pursuant to authority, and that the owner was properly created and is in good standing in its state of origin and is properly authorized to do business in the state where the Land is located.</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 20pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></td>
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">That the undersigned has not received any written notice of violation of any covenants, conditions
            or restrictions, if any, affecting the Land.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 20pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"></td>
        <td style="width: 18pt; font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">In order to induce First American Title Insurance Company (the &#8220;Company&#8221;) to issue its policy(ies)
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -1-</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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        <td style="width: 77.1pt; font: 10pt Times New Roman, Times, Serif"></td>
        <td style="width: 17.9pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">a.</font></td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="width: 77.1pt; font: 10pt Times New Roman, Times, Serif"></td>
        <td style="width: 17.9pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">b.</font></td>
        <td style="font: 10pt Times New Roman, Times, Serif; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The undersigned does hereby agree to indemnify and hold the Company harmless during the gap period
            between the last title examination of the Land that was conducted by, for and/or on behalf of the Company, and the time when the deed, assignments and any other documents creating priority of title are recorded in connection with the sale
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      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Seller / Owner:</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Ionis Gazelle, LLC, a Delaware corporation</font></p>
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        <td style="text-align: justify; width: 3%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">By:</font></td>
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        <td style="text-align: justify; width: 50%">&#160;</td>
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  </table>
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          <p style="margin-top: 0; margin-bottom: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Name: .</font></p>
          <p style="margin-top: 0; margin-bottom: 0"><font style="font: 10pt Times New Roman, Times, Serif">Title:</font></p>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif"><u>CALIFORNIA ALL-PURPOSE ACKNOWLEDGEMENT CIVIL CODE &#167;1189</u></font></p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="text-align: justify; border: Black 1pt solid"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">A notary public or other officer completing this certificate verifies only the identity of the individual who signed
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        -3-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>&#160;</b></font></p>
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      (which has legal title to a United States real property interest under local law) will be the transferor of the property and not the disregarded entity. To inform the transferee that withholding of tax is not required upon the disposition of a United
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Under penalties of perjury, I declare that I have examined this
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -2-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b><u>EXHIBIT M</u></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Form of APP Escrow Agreement</u></font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>POST-CLOSING ESCROW AGREEMENT</u></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>THIS POST-CLOSING ESCROW AGREEMENT</b> (this &#8220;<b>Agreement</b>&#8221;)








      is being entered into as of this ___ day of <u> </u> ______, 2022 (the &#8220;<b>Closing Date</b>&#8221;), by and among <b>IONIS GAZELLE, LLC</b>, a Delaware limited liability company (&#8220;<b>Seller</b>&#8221;), <b>2850 2855 &amp; 2859 GAZELLE OWNER (DE) LLC</b>, a
      Delaware limited liability company (&#8220;<b>Buyer</b>&#8221;) and <b>FIRST AMERICAN TITLE INSURANCE COMPANY </b>(&#8220;<b>Escrow Holder</b>&#8221;) and may be relied upon by Seller, Buyer, and Escrow Holder.</font></p>
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      certain Purchase and Sale Agreement dated as of <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>, 2022 (the &#8220;<b>Purchase Agreement</b>&#8221;), whereby Seller agreed to sell and Buyer agreed to buy that certain real property and improvements, as more particularly described
      therein. Capitalized terms not otherwise defined herein are as defined in the Purchase Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 85.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Buyer&#8217;s Affiliate and Seller&#8217;s
      Affiliate are parties to that Purchase and Sale Agreement dated as of <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>&#160;<u>&#160;&#160;&#160;&#160;&#160;</u>, 2022 (the &#8220;<b>BTS Purchase Agreement</b>&#8221;) for the purchase and sale of Lots 21 and 22, Carlsbad, California (the &#8220;<b>BTS Parcel</b>&#8221;),








      as more particularly described therein.</font></p>
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      Purchase Agreement, (i) Buyer is obligated to deposit $5,000,000 (the &#8220;<b>Additional Purchase Price</b>&#8221;) into an escrow account with Escrow Holder at Closing; and (ii) the Additional Purchase Price shall be disbursed to Seller if the &#8220;Closing&#8221; as
      defined in the BTS Purchase Agreement (the &#8220;<b>BTS Closing</b>&#8221;) occurs pursuant to the BTS Purchase Agreement.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">D.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Buyer and Seller desire to set forth
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Agreement</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      consideration of the mutual promises contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, Seller, Buyer and Escrow Holder hereby agree as follows:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Additional Purchase Price.</u>
      At Closing, Buyer shall deposit the Additional Purchase Price in escrow with Escrow Holder in accordance with Section 2.2(b) of the Purchase Agreement. The Additional Purchase Price shall be held by Escrow Holder in an interest-bearing account of the
      type customarily used to hold escrow funds and all interest and earnings shall be paid to the party whom the Additional Purchase Price is released to pursuant to Section 2 below.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Release of Additional Purchase
        Price</u>. If the BTS Closing occurs on the &#8220;Closing Date&#8221; under the BTS Purchase Agreement, then the Additional Purchase Price shall be promptly disbursed to Seller by Escrow Holder. If, however, the sale of the BTS Parcel is not consummated on
      the &#8220;Closing Date&#8221; under the BTS Purchase Agreement for any reason or if the BTS Purchase Agreement terminates prior to the Closing thereunder, then the Additional Purchase Price shall be promptly disbursed to Buyer.</font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Escrow Procedures.</u></font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">a.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Escrow Holder has the right to enforce the
      terms and conditions of this Agreement. Buyer and Seller do hereby jointly and severally agree that Escrow Holder shall incur no liability whatsoever in connection with its good faith performance under this Agreement, including without limitation,
      loss or damage resulting from the following:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">i.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The financial status or insolvency
      of any other party, or any misrepresentation made by any other party;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 101.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">ii.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any legal effect, insufficiency, or
      undesirability of any instrument deposited with or delivered by or to Escrow Holder or exchanged by the parties hereunder, whether or not Escrow Holder prepared such instrument;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 98.25pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">iii. &#160;&#160;&#160;&#160;&#160;&#160;&#160;The default, error, action or
      omission or any other party to the escrow;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 98.25pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">iv.&#160;&#160;&#160;&#160;&#160;&#160;&#160; Any loss or impairment of funds that
      have been deposited in escrow while those funds are in the course of collection or while those funds are on deposit in a financial institution if such loss or impairment results from the failure, insolvency or suspension of a financial institution,
      or any loss or impairment of funds due to the invalidity of any draft, check, document or other negotiable instrument delivered to Escrow Holder;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">v.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The expiration of any time limit or
      other consequence of delay unless a properly executed settlement instruction, executed by Escrow Holder has instructed Escrow Holder to comply with said time limit;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">vi.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Escrow Holder&#8217;s compliance with any
      legal process, subpoena, writ, order, judgment or decree of any court, whether issued with or without jurisdiction and whether or not subsequently vacated, modified, set aside or reversed;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">vii.&#160;&#160;&#160;&#160;&#160;&#160;&#160;Upon completion of the disbursement
      of the funds and delivery of the instruments, if any, Escrow Holder shall be automatically released and discharged of its escrow obligations hereunder; and</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 98.25pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">viii.&#160;&#160;&#160;&#160;&#160;&#160;The obligations of Buyer and Seller
      shall apply to and be for the benefit of agents of Escrow Holder employed by it for services in connection with this escrow, as well as for the benefit of Escrow Holder.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 89pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">b.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Buyer and Seller do hereby jointly and
      severally release and waive any claims they may have against Escrow Holder, which may result from its performance in good faith of its function under this Agreement, including, but not limited to, a delay in the electronic wire transfer of funds.
      Notwithstanding the foregoing, Escrow Holder shall be liable only for loss or damage caused directly by its negligence or willful misconduct while performing as Escrow Holder under this Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">EXHIBIT M<br>
        -2-</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">c.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Escrow Holder shall be entitled to rely
      upon the authenticity of any signature and the genuineness and validity of any writing received by Escrow Holder relating to this Agreement. Escrow Holder may rely upon any oral identification of a party notifying Escrow Holder orally as to matters
      relating to this Agreement if such oral notification is permitted hereunder. Escrow Holder is not responsible for the nature, content, validity, or enforceability of any of the escrow documents except for those documents prepared by Escrow Holder.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">d.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In the event of any disagreement between
      the parties hereto resulting in conflicting instructions to, or adverse claims or demands upon Escrow Holder with respect to the release of any escrow funds, Escrow Holder may refuse to comply with any such instruction, claim, or demand so long as
      such disagreement shall continue and in so refusing, Escrow Holder shall not release such escrow funds. Escrow Holder shall not be or become liable in any way for its failure or refusal to comply with any such conflicting instructions or adverse
      claims or demands and it shall be entitled to continue to refrain from acting until such conflicting instructions or adverse claims or demands (a) shall have been adjusted by agreement and it shall have been notified in writing thereof by the parties
      hereto, or (b) shall have finally been determined in a court of competent jurisdiction. Escrow Holder may bring an interpleader action when it, in good faith, believes that conflicting demands have been made or such instructions are unclear or
      ambiguous. Once any funds are interpleaded, Escrow Holder shall be released from all further liability of any nature in connection therewith or with the Additional Purchase Price. Such action shall not be deemed to be the &#8220;fault&#8221; of Escrow Holder,
      and Escrow Holder may lay claims to or against the funds for its reasonable costs and attorneys&#8217; fees in connection with the same, through final appellate review. To that end, the parties hereto, other than Escrow Holder, agree to indemnify Escrow
      Holder from all such attorneys&#8217; fees, court costs and expenses.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">e.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Escrow Holder may, at its sole discretion,
      resign by giving thirty (30) days written notice thereof to the parties hereto. The parties shall furnish to Escrow Holder written instructions for the release of any escrow funds. If Escrow Holder shall not have received such written instructions
      within the thirty (30) days, Escrow Holder may petition any court of competent jurisdiction for the appointment of a successor Escrow Holder and, upon such appointment, deliver the escrow funds to such successor.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">f.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The parties hereto do hereby certify that
      they are aware that the Federal Deposit Insurance Corporation (&#8220;<b>FDIC</b>&#8221;) coverages apply only to a cumulative maximum amount of $250,000 for each individual deposit for all of the depositor&#8217;s accounts at the same or related institution. The
      parties hereto further understand that certain banking instruments such as, but not limited to, repurchase agreements and letters of credit are not covered at all by FDIC insurance. All amounts held under this Agreement shall be in an interest
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        -3-</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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      assumes no responsibility for, nor will the parties hereto hold Escrow Holder liable for, a loss occurring which arises from the fact that the amount of the above account may cause the aggregate amount of any individual depositor&#8217;s accounts to exceed
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      email, provided that a confirmation copy is delivered within one (1) business day by the method set forth in clause (a) or (b) of this Section 7. All such notices, demands, requests or other communications shall be deemed to have been given for all
      purposes of this Agreement upon the earlier to occur of the date of receipt or the date of first refusal, except that whenever under this Agreement a notice is either received on a day which is not a business day or is required to be delivered on or
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      <tr style="vertical-align: top; text-align: justify">
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  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 2in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></p>
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      Email: [***]</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

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            <font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th </sup>Floor</font></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -4-</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">First American Title Insurance Company <br>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">[Signatures on Next Page]</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        -5-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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            and other improvements thereon, located at 2850, 2855 &amp; 2859 Gazelle Court, Carlsbad, 92010 California consisting of approximately 246,699 gross square feet, and the appurtenances thereto. The square footage of the Premises set forth above
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        <td style="font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The period commencing on the Commencement Date and ending on the Expiration Date.</font></td>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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        <td style="font: 10pt Times New Roman, Times, Serif">&#160;</td>
      </tr>
      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
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        <td style="font: 10pt Times New Roman, Times, Serif">&#160;</td>
      </tr>
      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="font: 10pt Times New Roman, Times, Serif">
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Boston, MA 02110&#160;</font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">Attn: Abby Mondani</font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">and</font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">DLA Piper LLP (US)&#160;</font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attn: John L. Sullivan, Esq.&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">and all legal notices shall also be sent to:&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">[***]</font></p>
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      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>TABLE OF CONTENTS</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr>
        <td colspan="3" style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">ARTICLE 1 LEASE OF PREMISES; TERM</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
      </tr>
      <tr>
        <td colspan="3" style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
      </tr>
      <tr>
        <td style="vertical-align: top; width: 5%">&#160;</td>
        <td style="vertical-align: top; width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.1</font></td>
        <td style="vertical-align: top; width: 85%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lease</font></td>
        <td style="vertical-align: bottom; width: 5%; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
      </tr>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.2</font></td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">As Is; No Representations</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.3</font></td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Holdover</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4</font></td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Extension Option</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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      <tr>
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      </tr>
      <tr>
        <td colspan="2" style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1</font></td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Base Rent and Additional Rent</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4</font></td>
      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
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        <td style="vertical-align: top">&#160;</td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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      <tr>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">48</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">49</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">49</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">49</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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      <tr>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">50</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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      <tr>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">50</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">51</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">52</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">52</font></td>
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        <td style="vertical-align: top">&#160;</td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">53</font></td>
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        <td style="vertical-align: bottom; width: 5%; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">53</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.2</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
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        <td style="width: 85%"><font style="font-size: 10pt">Legal Description of the Premises</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit C</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Form of Tenant Estoppel Certificate</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Form of Memorandum of Lease</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit E</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Form of SNDA</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit F</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Form of Non-Disclosure and Confidentiality Agreement</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit G</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Landlord Signage</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit H</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Plans and Specifications for Conference Center Alterations</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Commencement and Termination Date Agreement</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit K</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Tenant Construction Manual</font></td>
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        <td style="padding-top: 10pt"><font style="font-size: 10pt">Exhibit L</font></td>
        <td style="padding-top: 10pt"><font style="font-size: 10pt">Tenant Standard Operating Procedures</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">This Lease Agreement (this &#8220;<b>Lease</b>&#8221;), dated _____________, 2022 (the &#8220;<b>Effective Date</b>&#8221;), is made between 2850
    2855 &amp; 2859 Gazelle Owner (DE) LLC, a Delaware limited liability company (&#8220;<b>Landlord</b>&#8221;), and Ionis Pharmaceuticals, Inc., a Delaware corporation (&#8220;<b>Tenant</b>&#8221;).</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 1&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>LEASE OF PREMISES; TERM</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Lease</u>. Landlord hereby leases to
    Tenant, and Tenant hereby leases from Landlord, the Premises for the Term. Landlord and Tenant acknowledge that Tenant is in possession of the Premises as of the Commencement Date and accepts the Premises in its &#8220;as is&#8221; condition with all faults. All
    of the terms and covenants of this Lease shall be effective as of the Effective Date. After the Commencement Date, Tenant and Landlord shall execute, acknowledge and deliver a written agreement in the form attached hereto as <u>Exhibit J</u>
    memorializing the Commencement Date, the Expiration Date, the original Term, and the commencement and termination dates of the Extension Terms if such are exercised.</p>
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    utilities serving the Premises, any structural components of the improvements or the condition of any Building system), (b) the restrictions that may affect the conduct of Tenant&#8217;s business in, or Tenant&#8217;s use of, the Premises, or any other rights or
    benefits under this Lease, (c) the suitability of the Premises for Tenant&#8217;s intended Permitted Use, or (d) compliance with Environmental Laws at the Premises or any environmental conditions at, or Hazardous Materials on, under, above, emanating to or
    from, or having emanated to or from, the Premises. TENANT EXPRESSLY WAIVES ANY WARRANTY OF CONDITION OR OF HABITABILITY OR SUITABILITY FOR OCCUPANCY, USE, HABITATION, FITNESS FOR A PARTICULAR PURPOSE OR MERCHANTABILITY, EXPRESS OR IMPLIED, RELATING TO
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    codes, ordinances, rules and regulations of governmental authorities, committees, associations, or other regulatory committees, agencies or governing bodies having jurisdiction over the Premises or any portion thereof, Landlord or Tenant, including
    both statutory and common law and Environmental Laws. &#8220;<b>Environmental Laws</b>&#8221; means any applicable present and future federal, state and local laws, statutes, ordinances, rules, and regulations, as well as common law, relating to protection of
    human health, natural resources or the environment or governing the use, transport, or disposal of biological, bio-hazardous wastes, or radiological elements. The term &#8220;Environmental Laws&#8221; includes, but is not limited to, the Comprehensive
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    Health and Safety Code &#167;25249.5, et seq., and all other applicable federal, state and local laws, regulations, ordinances, rules, and orders that are equivalent or similar to the laws recited above, or otherwise relate to human health, natural
    resources or the environment, in each case together with their implementing regulations, guidelines, rules, or orders, and all state, regional, county, municipal, and other local laws, regulations, ordinances, rules, and orders that are equivalent or
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    shall (a) be a tenant at sufferance only, (b) be liable to perform all of the obligations of Tenant set forth in this Lease, and (c) (i) for the first ninety (90) days following the Termination Date, pay Base Rent at a rate of one hundred twenty-five
    percent (125%) of the monthly Base Rent in effect immediately prior to the Termination Date, and (ii) for each month thereafter, pay Base Rent at a rate of one hundred fifty percent (150%) of the monthly Base Rent in effect immediately prior to the
    Termination Date, prorated on a daily basis. If Tenant retains possession of any portion of the Premises for more than thirty (30) days following the Termination Date without Landlord&#8217;s written consent, Tenant shall also pay to Landlord all damages,
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      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">1.4</td>
        <td style="text-align: justify"><u>Extension Option</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">1.4.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Exercise of Extension Option</u>. Tenant
    shall have two (2) successive options (each, an &#8220;<b>Extension Option</b>&#8221;) to extend the Term of this Lease for a period of five (5) years each (each, an &#8220;<b>Extension Period</b>&#8221;), on the same terms and conditions in effect under this Lease
    immediately prior to the Extension Period, except that Base Rent shall be determined as set forth below and Tenant shall have no further right to extend the Term of this Lease after the end of the second (2<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup>) Extension Period; provided, however, it shall be a condition of Tenant&#8217;s exercise of the Extension Option that Tenant also exercise the corresponding &#8220;Extension Option&#8221; as defined in the Companion Lease.
    If Tenant exercises an Extension Option, such extension shall apply to the entire Premises. Tenant may exercise an Extension Option only by giving Landlord irrevocable and unconditional written notice thereof (the &#8220;<b>Extension Notice</b>&#8221;) on or
    before the date which is twelve (12) months prior to the commencement date of each applicable Extension Period and such Extension Period shall commence on the day immediately succeeding the expiration date of the preceding Term or the preceding
    Extension Period, as the case may be, and shall end at midnight Eastern Time on the last day of the applicable Extension Period. Such exercise shall, at Landlord&#8217;s election, be null and void if any Event of Default shall have occurred and is continuing
    at the date of such notice. Upon delivery of the Extension Notice, Tenant shall be irrevocably bound to lease the Premises for the Extension Period. If Tenant shall fail to timely exercise the Extension Option in accordance with the provisions of this
    <u>Section 1.4</u>, then the Extension Option shall terminate, and shall be null and void and of no further force and effect. If this Lease or Tenant&#8217;s right to possession of the Premises shall terminate in any manner whatsoever before Tenant shall
    exercise the Extension Option, then immediately upon such termination the Extension Option shall simultaneously terminate and become null and void. Time is of the essence with regard to this <u>Section 1.4</u>.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">1.4.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Base Rent Determination</u>. The Base Rent
    starting on the Commencement Date of each Extension Period and continuing for sixty (60) months thereafter will be ninety-five percent (95%) of the then-prevailing market rate for new leases for comparable life sciences office and lab space to the
    Premises in comparable buildings to the Buildings in the Market Area (defined below) that a willing, comparable, non-equity tenant (excluding sublease and assignment transactions) would pay, and a willing, comparable landlord would accept, at arm's
    length, for a similar life sciences laboratory and research space in a first-class or &#8220;Class A&#8221; property ("<u>Fair Market Rent</u>"); provided, however, in no event shall the Fair Market Rent rate per month for the first year of each Extension Period
    be less than 103% of the Base Rent rate for the last month of the immediately preceding portion of the Term. Thereafter, escalations in the Base Rent shall be established using standard market escalations in the determination of Fair Market Rent, but
    in no event shall escalations in Base Rent be increased by less than three percent (3%) on each annual anniversary of the Commencement Date of the Extension Term. Fair Market Rent will reflect all monetary and non-monetary considerations and other
    relevant factors taken into account for comparable transactions, including, without limitation, the location of the Premises, age, quality and layout of the existing improvements in the Premises, brokerage commissions, improvements paid for by tenant
    improvement allowances, moving allowances, and all other relevant tenant concessions. Fair Market Rent will be adjusted to take into account the size of the Premises, the length of the Extension Period, and the credit of Tenant. The term &#8220;<b>Market
      Area</b>&#8221; means the real estate market area that includes Carlsbad, Sorrento Valley, Sorrento Mesa, University Town Center, and Delmar Heights.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">1.4.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Fair Market Rent</u>. Landlord will notify
    Tenant of its determination of the Fair Market Rent (consistent with the methodology reflected above) for the applicable Extension Period no later than ninety (90) days prior to the commencement date of the applicable Extension Period. If Tenant
    delivers written notice to Landlord within ten (10) business days after its receipt of Landlord's determination of Fair Market Rent whereby Tenant disagrees with Landlord's determination of the Fair Market Rent, Tenant shall include in its notice
    Tenant&#8217;s determination of the Fair Market Rent, and Landlord and Tenant will diligently and in good-faith confer for a period of thirty (30) days thereafter (the &#8220;<b>Negotiation Period</b>&#8221;) in an attempt to agree on the Fair Market Rent. If Landlord
    and Tenant are unable to agree on the Fair Market Rent during the Negotiation Period, then, within five (5) business days after the expiration of such period, Landlord and Tenant shall jointly appoint an independent arbitrator (the &#8220;<b>Arbitrator</b>&#8221;)
    who shall not have previously been employed by or otherwise worked with either Landlord or Tenant with experience in real estate activities, including at least ten (10) years&#8217; experience serving as a broker, appraiser and/or attorney in leasing
    transactions involving commercial life sciences laboratory and research space of comparable size and Class A quality to the Premises (collectively, the &#8220;Qualifications&#8221;), which Arbitrator shall, within twenty (20) days following the Arbitrator&#8217;s
    appointment, determine and report in writing to Landlord and Tenant the by selecting either Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent for the Extension Period, according to whichever of the applicable determinations is closer to the
    Fair Market Rent, as determined by the Arbitrator. If Landlord and Tenant cannot agree on the Arbitrator in accordance with the foregoing, Landlord or Tenant may apply to the American Arbitration Association to appoint the Arbitrator in accordance with
    the aforementioned criteria. The Arbitrator shall have no discretion other than to select Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent as aforesaid. The costs of the Arbitrator shall be shared equally by Landlord and Tenant, and each of
    Landlord and Tenant shall reasonably cooperate with the Arbitrator in providing documentation and any other reasonable evidence regarding how Landlord or Tenant, as applicable, arrived at its determination of the Fair Market Rent. If the Renewal Period
    commences prior to the final determination of the Fair Market Rent, Tenant shall pay to Landlord the monthly rate in effect immediately prior to the commencement of the applicable Renewal Period, subject to adjustment upon resolution of such dispute.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">1.4.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>General</u>. Notwithstanding any provision of
    this Section to the contrary, the Extension Option shall be void, at Landlord's election, if (i) Tenant is in default hereunder, after any applicable notice and cure periods have expired, at the time Tenant elects to extend the Term or at the time the
    Term would expire but for such extension, or (ii) any Transfer has occurred under Article 5 of the Lease (other than a Permitted Transfer, or a sublease(s) comprising less than twenty-five percent (25%) of the Premises).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 2<br>
    RENT</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">2.1</td>
        <td style="text-align: justify"><u>Base Rent and Additional Rent</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall pay to Landlord, without notice or
    demand and without deduction or set-off of any amount for any reason whatsoever, the annual Base Rent in equal monthly payments on or before the first day of each full calendar month during the Term. Base Rent as well as any other amounts payable by
    Tenant to Landlord under the terms of this Lease shall be paid by wire or electronic transfer of funds pursuant to directions provided to Tenant by Landlord. In addition to Base Rent, Tenant shall pay to Landlord a property management fee (&#8220;<b>Management








      Fee</b>&#8221;) of one percent 1%) of the gross annual revenue form the Premises, which amount shall be paid in equal monthly payments on the same date and in the same manner as Base Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>If the Commencement Date is not the first day of
    a calendar month, Tenant shall pay to Landlord on the Commencement Date the prorated Base Rent for period from the Commencement Date until the end of the calendar month in which the Commencement Date occurs. Base Rent due for any partial calendar month
    at the end of the Term shall also be prorated and paid on the first day of such calendar month. Tenant shall pay to Landlord all items of Rent (as defined below), without deduction or offset and without notice or demand (except as specifically provided
    in this Lease in respect of Additional Rent (as defined below)), and Tenant shall deliver such payments to the payment address set forth in the Basic Lease Information, or to such other person, at such other place, or in such other manner as Landlord
    may designate by giving to Tenant Notice (as defined below) thereof. &#8220;<b>Additional Rent</b>&#8221; means all other amounts payable by Tenant to Landlord in accordance with this Lease, other than Base Rent. &#8220;<b>Rent</b>&#8221; means all amounts payable by Tenant
    to Landlord in accordance with this Lease, including, but not limited to Base Rent and Additional Rent.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord shall, on or within thirty (30) days
    prior to each Adjustment Date, calculate the Escalation after the United States Department of Labor publishes the Index on which the amount of the increase will be based. Landlord&#8217;s determination of the Escalation shall be binding absent manifest
    error. Landlord shall give written notice of the Escalation, multiplied by the number of installments of rent due under this Lease since the Adjustment Date. Tenant shall pay this amount, together with the monthly rent next becoming due under this
    Lease, and shall thereafter pay the monthly rent due under this Lease at this increased rate, which shall constitute Base Rent. Landlord's failure to make the required calculations promptly shall not be considered a waiver of Landlord's rights to
    adjust the monthly Base Rent due, nor shall it affect Tenant's obligations to pay the increased Base Rent, subject to this Section 2.1.3. If Landlord does not deliver its calculation of the Escalation within twelve (12) months after the applicable
    Adjustment Date, Tenant may provide Landlord with a written request for the calculation of the Escalation, and, if Landlord fails to provide the calculation of Escalation (which request shall include, in bold and prominent print on the first page, a
    notation that &#8220;<b>FAILURE TO RESPOND TO THIS REQUEST WITHIN 30 DAYS MAY RESULT IN THE LOSS OF RIGHTS PURSUANT TO SECTION 2.1.3 OF THE LEASE</b>&#8221;) within thirty (30) days after Tenant&#8217;s written request, Tenant shall not be required to so pay the
    increased Base Rent in arrearage for the applicable period based on an Escalation; provided, however, the foregoing waiver of Tenant&#8217;s obligation to pay arrearage amounts for the applicable period shall not affect Landlord&#8217;s calculation of any future
    Escalations. If the Index is changed so that the base year differs from that in effect on the Commencement Date, the Index shall be converted in accordance with the conversion factor published by the United States Department of Labor, Bureau of Labor
    Statistics. If the Index is discontinued or revised during the Term, the government index or computation with which it is replaced shall be used to obtain substantially the same result as if the Index had not been discontinued or revised. The &#8220;<b>Adjustment









      Date</b>&#8221; means the first anniversary of the Commencement Date and on each successive anniversary thereafter during the Term, including any exercised Extension Period.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">2.2</td>
        <td style="text-align: justify"><u>Expenses; Taxes; Insurance Expenses</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Expenses</u>. Tenant shall perform all
    obligations with respect to the maintenance, operation, repair and replacement of the Premises and shall pay directly for all costs and expenses incurred in connection therewith, including, but not limited to: all insurance, maintenance, repair and
    replacement of any improvements (including, without limitation, the Buildings, the structural and nonstructural components of the Buildings, the Building systems, equipment (owned and maintained), the foundation, roof, walls, heating, ventilation, air
    conditioning, plumbing, electrical, mechanical, utility (owned and maintained) and safety systems, paving and parking areas, roads and driveways); maintenance of exterior areas such as gardening and landscaping, snow removal and signage; maintenance
    and repair of roof membrane, flashings, gutters, downspouts, roof drains, skylights and waterproofing; painting; lighting; cleaning; refuse removal; security; utilities for, or the maintenance of, outside areas; Premises personnel costs; rentals or
    lease payments paid by Tenant for rented or leased personal property used in the operation or maintenance of the Premises; and fees for required licenses and permits, including in order to operate for the Permitted Use. In addition to the foregoing,
    Tenant shall perform the work described in <u>Exhibit I</u>, at Tenant&#8217;s sole cost and expense, within the following time periods: (i) items identified as a Repair Type &#8220;Immediate&#8221; on <u>Exhibit I</u> shall be completed within six (6) months after
    the Commencement Date and (ii) items identified as a Repair Type &#8220;Short Term&#8221; on <u>Exhibit I</u> shall be completed within twelve (12) months after the Commencement Date (with &#8220;replacement reserve items&#8221; to be monitored and addressed as noted).</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Taxes</u>. Subject to Tenant&#8217;s right to
    contest Taxes as set forth below, Tenant will pay directly all Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable. Landlord and Tenant shall cooperate to place all Taxes in the name of Tenant,
    however, if and to the extent any Taxes are billed to Landlord, then Tenant shall pay the same upon receipt of such bill from Landlord and provide Landlord with evidence of such payment promptly thereafter. In any event, Tenant shall pay all Taxes
    prior to the date due. &#8220;<b>Taxes</b>&#8221; means all real property taxes and other assessments on the Premises, including, but not limited to, real estate taxes, personal property taxes, transfer taxes, documentary stamps or taxes, fees, assessments and
    other charges of any kind or nature, whether general, special, ordinary, or extraordinary (without regard to any different fiscal year used by such governmental authority) that are levied in respect of this Lease or the Premises (or Landlord&#8217;s interest
    therein), or in respect of any improvement, fixture, equipment, or other property of Landlord, real or personal, located at the Premises, and used in connection with operation of the Premises. Tenant and Landlord acknowledge that Proposition 13 was
    adopted by the voters of the State of California in the June 1978 election (&#8220;<b>Proposition 13</b>&#8221;) and that assessments, taxes, fees, levies and charges may be imposed by governmental agencies for such services as fire protection, street, sidewalk
    and road maintenance, refuse removal and for other governmental services formerly provided without charge to property owners or occupants, and, in further recognition of the decrease in the level and quality of governmental services and amenities as a
    result of Proposition 13, Taxes shall also include any governmental or private assessments or contribution towards a governmental or private cost-sharing agreement charged to the Premises for the purpose of augmenting or improving the quality of
    services and amenities normally provided by governmental agencies. Taxes shall not include (i) Landlord&#8217;s corporate franchise taxes, estate taxes, inheritance taxes or net income taxes, or (ii) transfer taxes or other taxes incurred in connection with
    Landlord&#8217;s sale of the Premises or any interest therein, other than taxes resulting from Proposition 13 reassessment. Tenant shall furnish to Landlord, within thirty (30) days after the last day when any Tax must be paid by Tenant as provided in this
    Section 2.2.2, official receipt of the appropriate taxing authority or other proof satisfactory to Landlord, evidencing the payment thereof. Tenant shall have the right, at Tenant&#8217;s sole cost and upon reasonable prior notice to Landlord, to initiate
    and prosecute any proceeding for the purpose of contesting the assessed valuation of the Premises or any personal property for tax purposes in good faith; provided, that this right to contest shall not be deemed or construed to relieve, modify or
    extend Tenant&#8217;s obligation to pay any Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable and that prior to any such contest, Tenant (a) pays the Tax under protest, (b) obtains and maintains a stay of
    all proceedings for enforcement and collection by posting a bond or other security required by law, or (c) if Tenant lawfully withholds payments of any contested amounts of Taxes during the contest, Tenant has or establishes unrestricted cash reserves
    to be held by Landlord in an amount equal to 125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contest; provided, however, that Landlord shall (1) promptly release such
    reserve upon resolution of such contest, and/or (2) use such reserve to pay Taxes directly to the applicable taxing authority following resolution of such contest. Tenant shall provide Landlord with all notices received or sent to the taxing
    authorities, as well as regular updates relating to any such contest and afford Landlord an opportunity to participate in all such proceedings. Tenant shall indemnify and defend Landlord and save Landlord harmless from all losses, judgments, costs
    (including without limitation, attorneys&#8217; fees), liabilities and expenses incurred in connection with such proceedings and shall, promptly after the final determination of such contest, fully pay and discharge the amounts which shall be levied,
    assessed, charged or imposed or be determined to be payable therein or in connection therewith, together with all penalties, fines, costs and expenses thereof or in connection therewith). Landlord shall have the right to (a) contest or dispute any
    Taxes (or file an appeal related thereto), without Tenant&#8217;s prior written consent, at Landlord&#8217;s sole cost and expense, or (b) request that Tenant contest or dispute such Taxes (or file an appeal related thereto), in which event, Tenant, in Tenant&#8217;s
    sole discretion, may agree to contest or dispute such Taxes, at Tenant&#8217;s sole cost and expense. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord, Landlord, at its option, may require Tenant to make monthly
    estimated payments to Landlord on account of Taxes. The monthly payments shall be one twelfth (1/12th) of the amount of Taxes due for the applicable year as reasonably estimated by Landlord and shall be payable as Additional Rent on or before the first
    day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. So long as no Event of Default is then continuing, any amounts received by Landlord pursuant to the immediately
    preceding sentence shall be disbursed to Tenant by Landlord for payment to the applicable taxing authority (or paid to the applicable taxing authority directly by Landlord) when directed by Tenant, accompanied by evidence of the amount due. Upon
    Tenant&#8217;s request, Landlord shall provide Tenant with evidence of any such payments of Taxes made directly by Landlord.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.2.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Insurance</u>. Tenant shall
    reimburse or, at Landlord&#8217;s request, pay directly, all premiums, deductibles, and other costs incurred by Landlord in connection with obtaining and maintaining the insurance coverage described in <u>Section 6.2.1</u> below (collectively, the &#8220;<b>Insurance








      Expenses</b>&#8221;). Tenant shall pay the Insurance Expenses no later than fifteen (15) days after demand. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord, Landlord, at its option, may require Tenant to make
    monthly estimated payments to Landlord on account of Insurance Expenses. The monthly payments shall be one twelfth (1/12th) of the amount of Insurance Expenses due for the applicable year as reasonably estimated by Landlord and shall be payable as
    Additional Rent on or before the first day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. If Landlord requires monthly payments of the Insurance Expenses, Landlord
    will use reasonable efforts to provide a statement reconciling such payments within ninety (90) days after the end of each calendar year, and any underpayments shall paid by Tenant within fifteen (15) days after Tenant&#8217;s receipt of the statement, and
    any overpayments shall be credited to the next payment of Rent that becomes due under the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">2.3</td>
        <td style="text-align: justify"><u>Net Lease.</u></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Absolute Triple Net Lease</u>. It is intended
    by the parties that this Lease be an absolute &#8220;triple net lease,&#8221; imposing upon Tenant the obligation to pay all charges of every kind and nature in connection with the use, operation, management, maintenance, repair, and occupancy of the Premises,
    whether or not recited herein and whether foreseeable or unforeseeable, including, but not limited to, utilities, fees, costs, real estate taxes, sales and use taxes, all operation, management, maintenance and repair costs associated with the Premises
    and the improvements located thereon and costs of compliance with Environmental Laws, except as expressly provided in this Lease. Tenant shall pay to Landlord, net throughout the Term, the Rent due hereunder free of any offset, abatement, or other
    deduction whatsoever, without notice or demand. Except to the extent due to the gross negligence or willful misconduct of, or breach of contract by, Landlord or any of Landlord&#8217;s assignees, agents, servants, employees, invitees and contractors (or any
    of Landlord&#8217;s assignees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Landlord Parties</b>&#8221;; any of them, a &#8220;<b>Landlord Party</b>&#8221;), Tenant assumes the sole responsibility for the condition, use, operation,
    maintenance, management and compliance with Environmental Laws of the Premises, and Landlord shall have no responsibility in respect thereof and shall have no liability for damage to Tenant&#8217;s personalty on any account or for any reason whatsoever.
    Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant shall not be required to pay, or reimburse Landlord for: (i) depreciation charges, penalties, premiums, interest and principal payments on mortgages and other debt costs,
    ground rental payments and real estate brokerage and leasing commissions incurred by Landlord; (ii) costs incurred for Landlord&#8217;s general overhead and any property or asset management fee other than as expressly set forth in this Lease; (iii) costs of
    selling or financing any of Landlord&#8217;s interest in the Premises; (iv) costs incurred by Landlord which are reimbursed by property insurance proceeds actually received by Landlord where such proceeds result from a claim subject to the provisions of
    Section 6.2.3. below; and (v) reserves in excess of commercially reasonable amounts for comparable properties (and such reserves shall only be payable by Tenant if required by Landlord&#8217;s lender or in accordance with commercially reasonable business
    practices for comparable properties).</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Payments to Third Parties</u>. Subject to <u>Section








      2.2.3(c)</u> below, Landlord and Tenant recognize that there may be recurring payments to third parties, including governmental entities, for various items including inspections of storm water retention areas, inspections of pump stations, fees for
    storm water runoff, and assessments for maintenance and repairs under a Title Instrument (as defined below). Tenant is solely responsible for paying any fees or expenses imposed by governmental regulations or third parties, including those that may be
    required to obtain, modify and maintain compliance with any permits, licenses and approvals required by Applicable Laws, including for the use of and operation at the Premises by Tenant for the Permitted Use, or allocated to the Premises under any such
    Title Instrument. Tenant acknowledges that matters of the type contemplated by this Section may not be known to Landlord until after this Lease has been signed by Landlord and Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Title Instruments</u>. In addition to the
    foregoing, during the term of this Lease, Tenant shall timely perform all obligations of the owner of the Premises under, and pay all expenses which the owner of the Premises may be required to pay in accordance with any declarations, covenants,
    conditions and restrictions or reciprocal easement agreements or any other documents or instruments that are of record now and affect the Premises (or of record in the future if created or filed by or with the consent of Tenant), including, without
    limitation, any documents or instruments recorded in connection with any Future Development (referred to collectively herein as the &#8220;<b>Title Instruments</b>&#8221;); provided, however, Tenant need not pay any debt service on loans that encumber the fee
    estate and that do not encumber Tenant&#8217;s leasehold estate and Tenant need not pay any rent on any lease that is senior in priority to this Lease. Tenant promptly shall comply with all of the terms and provisions of all Title Instruments, including all
    insurance requirements, regardless of whether any such requirements exceed the requirements otherwise set forth in this Lease. Notwithstanding the foregoing, except as provided in Section 10.5, Landlord shall not enter into new Title Instruments or
    modify existing Title Instruments during the Term without Tenant&#8217;s prior written consent, which may be withheld in Tenant&#8217;s reasonable discretion; provided, however, that Tenant&#8217;s prior written consent shall not be required with respect to (i) any
    financing obtained by Landlord secured by Landlord&#8217;s interest in the Premises, (ii) Title Instruments necessary to effectuate transfers to third-party purchasers of the Premises, or (iii) any new Title Instruments or the modification of existing Title
    Instruments that do not (x) materially and adversely affect Tenant&#8217;s use or occupancy of the Premises or (y) impose any fees or costs that would be payable by Tenant unless Landlord agrees to pay such fees.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">8</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">2.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Interest and Late Charge</u>. If Tenant
    fails to pay Rent as and when due and such failure continues for three (3) business days following written notice from Landlord, then, together with each payment of Rent that Tenant pays to Landlord after such payment is due, Tenant shall pay to
    Landlord the Late Charge (as defined below) and interest calculated on the amount of such payment over the period commencing on the day immediately following the day on which such payment was due and ending on the day on which Tenant pays to Landlord
    such payment at the rate of the lesser of six percent (6%) over the &#8220;Prime Rate&#8221; announced from time to time by Bank of America or its successor or the maximum lawful rate of interest. Notwithstanding the foregoing, Landlord shall not be required to
    provide prior notice of Tenant&#8217;s failure to pay Base Rent or any recurring obligation to pay Rent more than once during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be subject to the Late Charge and default
    interest provided above if Tenant fails to pay the amount when due and such failure continues for three (3) business days after the due date. &#8220;<b>Late Charge</b>&#8221; means, in respect of any such payment, five percent (5%) of such payment. In addition,
    Tenant shall pay to Landlord a reasonable fee for any checks returned by Tenant&#8217;s bank for any reason.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">2.5</td>
        <td style="text-align: justify"><u>Security Deposit/Letter of Credit</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Concurrently with Tenant&#8217;s execution of this
    Lease, and in lieu of a cash security deposit, Tenant shall provide a letter of credit (the &#8220;<b>Letter of Credit</b>&#8221;) in the amount set forth as the &#8220;Security Deposit/Letter of Credit&#8221; in the Basic Lease Information. Any cash security deposit drawn
    from the Letter of Credit may be mingled with other funds of Landlord and no fiduciary relationship shall be created with respect to such deposit, nor shall Landlord be liable to pay Tenant interest thereon.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Letter of Credit (i) shall be irrevocable
    and shall be issued by a commercial bank that has a financial condition reasonably acceptable to Landlord and that is otherwise an Eligible Bank (as defined below) and has an office in San Francisco, California that accepts requests for draws on the
    Letter of Credit; provided, Silicon Valley Bank shall be deemed an approved issuer of the Letter of Credit so long as Silicon Valley Bank remains an Eligible Bank, (ii) shall require only the presentation to the issuer (which may be in a location other
    than San Francisco if permitted on the basis of a fax or electronic submittal only) a certificate of the holder of the Letter of Credit stating that Landlord is entitled to draw on the Letter of Credit pursuant to the terms of the Lease, (iii) shall be
    payable to Landlord or its successors in interest as the Landlord and shall be freely transferable without cost to any such successor or any lender holding a collateral assignment of Landlord&#8217;s interest in the Lease, (iv) shall be for an initial term
    of not less than one year and contain a provision that such term shall be automatically renewed for successive one-year periods unless the issuer shall, at least forty five (45) days prior to the scheduled expiration date, give Landlord notice of such
    nonrenewal, (v) shall be transferrable by Landlord without any cost to Landlord or the transferee (or, if there is a transfer fee, Tenant shall pay such fee and such transfer shall not be conditioned upon payment of such fee), and (vi) shall otherwise
    be in form and substance reasonably acceptable to Landlord. Notwithstanding the foregoing, the term of the Letter of Credit for the final period shall be for a term ending not earlier than the date forty-five (45) days after the last day of the Term.
    In the event that the issuer ceases to be reasonably acceptable to Landlord, due to a deterioration in its financial condition or change in status that threatens to compromise Landlord&#8217;s ability to draw on the Letter of Credit as determined in good
    faith by Landlord or otherwise by its failure to be an Eligible Bank, then Tenant shall provide a replacement Letter of Credit from an issuer satisfying the terms of this <u>Section 2.5.2</u> within thirty (30) days after Landlord&#8217;s notice of such
    event. &#8220;<b>Eligible Bank</b>&#8221; shall mean shall mean a commercial or savings bank organized under the laws of the United States or any state thereof or the District of Columbia and having total assets in excess of $1,000,000,000.00 that shall be a
    financial institution having a rating of not less than BBB or its equivalent by Standard and Poors Corporation and subject to a Thompson Watch Rating of C or better.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Letter of Credit shall be held by, or for
    the benefit of Landlord, as security for the performance of the provisions hereof by Tenant, and if the Letter of Credit or portion thereof is applied by Landlord for the payment of any Rent or any other sum in default, then Tenant shall, upon demand
    therefor, restore the Letter of Credit to its original amount as provided in <u>Section 2.5.1</u> above. Tenant hereby irrevocably waives and relinquishes any and all rights, benefits, or protections, if any, Tenant now has, or in the future may have
    under any provision of law which (i) establishes the time frame by which a landlord must refund a security deposit under a lease, or (ii) provides that a landlord may claim from a security deposit only those sums reasonably necessary to remedy defaults
    in the payment of rent, or to repair damage caused by a tenant or to clean the subject premises, as required and subject to the provisions of this Lease. Tenant acknowledges and agrees that (A) any statutory time frames for the return of a security
    deposit are superseded by the express period identified in this <u>Section 2.5</u>, and (B) rather than be so limited, Landlord may claim from the security deposit (i) any and all sums expressly identified in this <u>Section 2.4</u>, above, and (ii)
    any additional sums reasonably necessary to compensate Landlord for any and all losses or damages caused by Tenant&#8217;s default of this Lease, including, but not limited to, all damages or rent due upon termination of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord shall be entitled to draw upon the
    Letter of Credit for its full amount or any portion thereof if (a) Tenant shall fail to perform any of its obligations under the Lease after the expiration of any applicable notice and cure period, or fail to perform any of its obligations under the
    Lease and transmittal of a default notice or the running of any cure period is barred or tolled by Applicable Law, or fail to perform any of its obligations under the Lease and any applicable notice and cure period would expire after the expiration of
    the Letter of Credit, or (b) not less than thirty (30) days before the scheduled expiration of the Letter of Credit, Tenant has not delivered to Landlord a new Letter of Credit in accordance with this Section; provided no such delivery shall be
    required if the Letter of Credit provides for automatic renewals in compliance with <u>Section 2.5.2</u>, and the issuer of the Letter of Credit has not sent a notice of non-renewal. Without limiting the generality of the foregoing, Landlord may, but
    shall not be obligated to, draw on the Letter of Credit from time to time in the event of a bankruptcy filing by or against Tenant and/or to compensate Landlord, in such order as Landlord may determine, for all or any part of any unpaid rent, any
    damages arising from any termination of the Lease in accordance with the terms of the Lease, and/or any damages arising from any rejection of the Lease in a bankruptcy proceeding commenced by or against Tenant. Landlord may, but shall not be obligated
    to, apply the amount so drawn to the extent necessary to cure Tenant&#8217;s failure.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Any amount of the Letter of Credit drawn in
    excess of the amount applied by Landlord to cure any such failure shall be held by Landlord as a cash security deposit for the performance by Tenant of its obligations under the Lease. If Tenant shall fail to perform any of its obligations under the
    Lease, Landlord may, but shall not be obliged to, apply the cash security deposit to the extent necessary to cure Tenant&#8217;s failure. After any such application by Landlord of the Letter of Credit or cash security deposit, as the case may be, Tenant
    shall reinstate the Letter of Credit to the amount originally required to be maintained under the Lease, within ten (10) business days of Landlord&#8217;s demand. Provided that Tenant is not then in default under the Lease, and no condition exists or event
    has occurred that after the expiration of any applicable notice or cure period would constitute such a default, within forty five (45) days after the later to occur of (i) the payment of the final Rent due from Tenant or (ii) the later to occur of the
    Term Expiration Date or the date on which Tenant surrenders the Premises to Landlord in compliance with Section 20 of the Lease, the Letter of Credit and any cash security deposit, to the extent not applied, shall be returned to the Tenant, without
    interest, and Landlord, upon request, shall confirm termination of the Letter of Credit with the issuer thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>In the event of a sale of the Buildings or
    lease, conveyance or transfer of the Buildings, Landlord shall transfer the Letter of Credit or cash security deposit to the transferee. Upon such transfer, the transferring Landlord shall be released by Tenant from all liability for the return of such
    security, and Tenant agrees to look to the transferee solely for the return of said security. The provisions hereof shall apply to every transfer or assignment made of the security to such a transferee. Tenant further covenants that it will not assign
    or encumber or attempt to assign or encumber the Letter of Credit or the monies deposited herein as security, and that neither Landlord nor its successors or assigns shall be bound by any assignment, encumbrance, attempted assignment or attempted
    encumbrance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">2.5.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord and Tenant acknowledge and agree that
    in no event or circumstance shall the Letter of Credit, any renewal thereof or substitute therefor or the proceeds thereof be (i) deemed to be or treated as a security deposit within the meaning of California Civil Code Section 1950.7, (ii) subject to
    the terms of such Section 1950.7, or (iii) intended to serve as a security deposit within the meaning of such Section 1950.7. The parties hereto (A) recite that the Letter of Credit is not intended to serve as a security deposit and such Section 1950.7
    and any and all other laws, rules and regulations applicable to security deposits in the commercial context (&#8220;<b>Security Deposit Laws</b>&#8221;) shall have no applicability or relevancy thereto, and (B) waive any and all rights, duties and obligations
    either party may now or, in the future, will have relating to or arising from the Security Deposit Laws. Notwithstanding the foregoing, to the extent California Civil Code 1950.7 in any way: (a) is determined to be applicable to this Lease or the
    Letter of Credit (or any proceeds thereof); or (b) controls Landlord&#8217;s rights to draw on the Letter of Credit or apply the proceeds of the Letter of Credit to any amounts due under this Lease or any damages Landlord may suffer following termination of
    this Lease, then Tenant fully and irrevocably waives the benefits and protections of Section 1950.7 of the California Civil Code, it being agreed that Landlord may recover from the Letter of Credit (or its proceeds) all of Landlord&#8217;s damages under this
    Lease and California law including, but not limited to, any damages accruing upon the termination of this Lease in accordance with this Lease and Section 1951.2 of the California Civil Code.</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 3</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>USE, COMPLIANCE WITH LAWS, HAZARDOUS MATERIALS, DOGS</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Use</u>. Tenant shall use the Premises
    solely for the Permitted Use, in a manner consistent with first-class life science buildings, and shall comply (and ensure that the Premises at all times comply) with all Applicable Laws. Tenant shall be solely responsible for the securing, modifying,
    maintaining, and compliance with any and all permits, licenses and approvals required or that may be required or otherwise in effect for the Permitted Use and under Environmental Laws in connection with Tenant&#8217;s use and operation of the Premises.
    Tenant shall not commit, or allow to commit, any waste of or injury to the Premises or create, maintain or exacerbate any nuisance thereon or therefrom. Landlord agrees to reasonably cooperate with Tenant, at Tenant&#8217;s sole cost and expense, in
    obtaining any permits, licenses and approvals required by Applicable Laws for the use of and operation at the Premises by Tenant for the Permitted Use, including, without limitation, by executing or joining in the execution of such applications and
    other documentation (the form and content of which shall be subject to Landlord&#8217;s reasonable approval) in Landlord&#8217;s name, solely as and because Landlord is the fee simple owner of the Premises, as may be necessary for obtaining such permits, licenses
    and approvals, all without cost or liability to Landlord. Tenant shall operate in a first-class manner and shall not exceed the density limit for the Buildings under Applicable Laws. Tenant shall not commit waste or cause a public nuisance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Compliance with Applicable Laws</u>.
    Tenant shall comply with all Applicable Laws and any agreements between Tenant and third parties with respect to the Premises and Tenant&#8217;s operation at the Premises. It is intended that the Tenant bear the sole risk of all present or future Applicable
    Laws, regulations and orders affecting the Premises, and the Landlord shall not be liable for their enforcement. Should there be any material noncompliance or alleged material noncompliance by Tenant with Applicable Laws or agreements between Tenant
    and third parties with respect to the Premises and Tenant&#8217;s operation at the Premises, Tenant shall promptly notify Landlord in writing of such actual or alleged noncompliance, which notice shall include (i) documentation that such actual or alleged
    noncompliance has been fully addressed and eliminated or, (ii) if such actual or alleged noncompliance has not been fully addressed and eliminated, a schedule to fully and expeditiously address and eliminate such actual or alleged noncompliance. The
    giving of such notice shall not relieve Tenant of any liability to Landlord or others for such actual or alleged noncompliance. To ensure Tenant&#8217;s compliance with Applicable Laws and Tenant&#8217;s performance of Tenant&#8217;s management, repair, maintenance, and
    compliance obligations hereunder, upon reasonable notice to Tenant and subject to and in accordance with Applicable Laws and reasonable confidentiality requirements pertaining to Tenant&#8217;s operations (provided such requirements do not impair or delay
    Landlord&#8217;s rights under this Section), Landlord may inspect or cause non-invasive independent third party inspections of the facility and Tenant&#8217;s operation to confirm compliance with Applicable Laws and Tenant&#8217;s management, repair, maintenance, and
    compliance obligations hereunder, at Landlord&#8217;s expense, except as otherwise provided in Section 3.3.7.</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">3.3</td>
        <td style="text-align: justify"><u>Hazardous Materials</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant, and any of Tenant&#8217;s assignees,
    sublessees, licensees, agents, servants, employees, invitees and contractors (or any of Tenant&#8217;s assignees, sublessees and/or licensees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Tenant Parties</b>&#8221;; any of
    them, a &#8220;<b>Tenant Party</b>&#8221;) (a) shall not, and shall not permit at any time, the handling, use, manufacture, release, storage, or disposal of Hazardous Materials in or about any portion of the Premises in violation of Applicable Laws, (b) shall
    always manage, handle, use, store, and dispose of such Hazardous Materials in a safe manner, according to prudent industry practice, and in compliance with Applicable Laws, and (c) shall at all times have any and all required permits, licenses and
    approvals required for or in connection with, the use and handling of Hazardous Materials at the Premises and at all times be in compliance with such required permits, licenses and approvals. &#8220;<b>Hazardous Materials</b>&#8221; means (a) any and all
    substances (whether solid, liquid or gas) defined, listed or otherwise classified or regulated as &#8220;biological compounds&#8221;, &#8220;bio-hazardous wastes&#8221;, &#8220;radiological elements&#8221;, &#8220;hazardous wastes,&#8221; &#8220;hazardous materials,&#8221; &#8220;hazardous substances,&#8221; &#8220;toxic
    substances,&#8221; &#8220;pollutants,&#8221; &#8220;contaminants,&#8221; &#8220;radioactive materials&#8221;, &#8220;toxic pollutants&#8221;, &#8220;solid wastes,&#8221; or other similar designations in, or otherwise subject to regulation under Environmental Laws, and (b) any other substances, constituents or wastes
    that are deemed to have a negative impact on human health or the environment, whether or not naturally occurring, or that are subject to Environmental Law, now or hereafter in effect, including but not limited to (A) petroleum, (B) refined petroleum
    products, (C) waste oil, (D) waste aviation or motor vehicle fuel and their byproducts, (E) asbestos, (F) lead in water, paint or elsewhere, (G) radon, (H) Polychlorinated Biphenyls (PCBs), (I) urea formaldehyde, (J) volatile organic compounds (VOC),
    (K) total petroleum hydrocarbons (TPH), (L) benzene derivative (BTEX), (M) poly- and perfluoroalkyl substances and other emerging contaminants, and (N) petroleum byproducts. Hazardous Materials further includes flammables, explosives, corrosive
    materials, radioactive materials, materials capable of emitting toxic fumes, hazardous wastes, toxic wastes or materials, and other similar substances, petroleum products and derivatives, and any substance subject to regulation by or under any
    Environmental Law. As between Landlord and Tenant, Tenant is deemed to be the operator of the Premises, the generator of any Hazardous Materials waste present at or generated at the Premises or as part of Tenant&#8217;s operations, and the owner of all
    Hazardous Materials at the Premises at any and all times during the Term. On or before the expiration or earlier termination of this Lease, Tenant shall remove from the Premises all Hazardous Materials introduced to the Premises by Tenant, any other
    Party or any other party other than Landlord during the Term of the Lease, regardless of whether such Hazardous Materials are included on the Hazardous Materials List or present at the Premises in concentrations which require removal under Applicable
    Laws. As used herein, the term &#8220;<b>Contamination</b>&#8221; means the presence of Hazardous Materials in the air, soil, surface and/or ground water in, on or under the Premises and/or any adjacent property at levels above those permitted by applicable
    Environmental Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord acknowledges that it is not the
    intent of this <u>Section 3.3</u> to prohibit Tenant from using the Premises for the Permitted Use. Tenant may operate its business according to best industry practices so long as the use or presence of Hazardous Materials is strictly and properly
    monitored according to all then applicable Environmental Laws, all Hazardous Materials at the Premises are used in the operation of Tenant&#8217;s business, and such use is consistent with similar first-class facilities engaged in the Permitted Use in the
    greater San Diego County area. Notwithstanding the foregoing, Tenant shall have no right to install any underground storage tanks at the Premises unless Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s
    sole and absolute discretion. In conducting its research activities using Hazardous Materials, Tenant shall not perform work at or above the risk category Biosafety Level 3 as established by the Department of Health and Human Services publication
    Biosafety in Microbiological and Biomedical Laboratories (5th Edition) (as it may be or may have been further revised, the &#8220;<b>BMBL</b>&#8221;) or such nationally recognized new or replacement standards as Landlord may reasonable designate, without the prior
    written approval of Landlord, which approval shall not be unreasonably withheld, conditioned, or delayed (and if such change in Tenant&#8217;s operation requires the approval of Landlord&#8217;s lender, the lender&#8217;s denial of approval shall be deemed a reasonable
    basis for Landlord to deny its approval); provided, however, Landlord&#8217;s approval of any operation above the risk category Biosafety Level 3 shall be in Landlord&#8217;s sole discretion. Tenant shall comply with all applicable provisions of the standards of
    the BMBL to the extent applicable to Tenant&#8217;s operations in the Premises.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>As a material inducement to Landlord to allow
    Tenant to use Hazardous Materials in connection with its business, Tenant agrees to deliver to Landlord prior to the Commencement Date a list identifying each type of Hazardous Materials (other than ordinary office and cleaning supplies used in
    cleaning of the office spaces within the Building) to be brought upon, kept, used, stored, handled, treated, generated on, or released or disposed of from, the Premises and setting forth any and all governmental approvals or permits required in
    connection with the presence, use, storage, handling, treatment, generation, release or disposal of such Hazardous Materials on or from the Premises (&#8220;<b>Hazardous Materials List</b>&#8221;). Upon Landlord&#8217;s request (not more than once per year, unless
    Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>, a release or threatened release of Hazardous Materials has occurred, or in connection with a sale, financing, refinancing, or recapitalization of
    Landlord&#8217;s interest in the Premises), or any time that Tenant is required to deliver a Hazardous Materials List to any governmental authority (e.g., the fire department) or an insurer in connection with Tenant&#8217;s use or occupancy of the Premises, Tenant
    shall deliver to Landlord a copy of such Hazardous Materials List. Tenant shall deliver to Landlord true and correct copies of the following documents (the &#8220;<b>Haz Mat Documents</b>&#8221;) relating to the use, storage, handling, treatment, generation,
    release or disposal of Hazardous Materials prior to the Commencement Date, or if unavailable at that time, concurrent with the receipt from or submission to a governmental authority: permits; licenses, approvals; reports and correspondence; storage and
    management plans; notice of violations of any Applicable Laws; fire safety plans; spill response plans; plans relating to the installation of any storage tanks to be installed in or under the Premises (provided, said installation of tanks shall only be
    permitted after Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s sole and absolute discretion with respect to underground storage tanks); all closure plans or any other documents required by any and
    all governmental authorities for any storage tanks installed in, on or under the Premises for the closure of any such tanks; and a Surrender Plan (to the extent surrender in accordance with Section 3.3.9 cannot be accomplished in three (3) months).
    Tenant is not required, however, to provide Landlord with any portion(s) of the Haz Mat Documents containing proprietary information of a proprietary nature that, in and of themselves, do not contain a reference to any Hazardous Materials or hazardous
    activities. It is not the intent of this Section to provide Landlord with information that could be detrimental to Tenant&#8217;s business should such information become possessed by Tenant&#8217;s competitors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except to the extent caused by the gross
    negligence or willful misconduct of, or breach of contract by, Landlord or Landlord Parties, Tenant releases Landlord and Landlord Parties from and agrees to indemnify, defend and hold Landlord and Landlord Parties harmless for, from and against any
    and all actions (including, without limitation, remedial or enforcement actions of any kind, administrative or judicial proceedings, and orders or judgments arising out of or resulting therefrom), costs, claims, damages (including, without limitation,
    punitive damages and damages based upon diminution in value of the Premises, or the loss of, or restriction on, use of the Premises), expenses (including, without limitation, legal, consultants&#8217; and experts&#8217; fees, court costs and amounts paid in
    settlement of any claims or actions), fines, forfeitures or other civil, administrative or criminal penalties, injunctive or other relief (whether or not based upon personal injury, property damage, or Contamination of, or adverse effects upon, the
    environment, water tables or natural resources), liabilities or losses (i) that arise prior to, during, or after the Term, as a result of the presence, suspected presence, release, or suspected release of any Hazardous Materials in or into the
    environment, including the air, soil, surface water, or groundwater at, on, about, under, emanating to or from, having emanated to or from, or within the Premises, or any portion thereof caused or exacerbated by, or otherwise attributable to, Tenant or
    any other party (other than Landlord or Landlord Parties) prior to the date that Tenant vacates the Premises in the condition required following the termination or earlier expiration of the Term, or (ii) that arise prior to, during, or after the Term,
    as a result of the breach by Tenant of any of its obligations under this Section 3.3, including in each case, without limitation, the cost of assessment, containment and/or removal of any such Hazardous Materials, the reasonable and necessary cost of
    any actions taken in response to a release of any such Hazardous Materials so that it does not migrate or otherwise cause or threaten danger to present or future public health, safety, welfare or the environment, and costs incurred to comply with
    Environmental Laws in connection with all or any portion of the Premises or the operation thereof (or any surrounding areas for which Tenant or Landlord has any legal liability or obligation) during the Term.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>EXCEPT AS OTHERWISE PROVIDED FOR HEREIN,
    LANDLORD LEASES AND WILL LEASE, AND TENANT TAKES AND WILL TAKE, THE PREMISES IN AN ENVIRONMENTALLY &#8220;AS IS&#8221; CONDITION, AND TENANT ACKNOWLEDGES THAT LANDLORD HAS NOT MADE AND WILL NOT MAKE, NOR SHALL LANDLORD BE DEEMED TO HAVE MADE, ANY WARRANTY OR
    REPRESENTATION, EXPRESS OR IMPLIED, WITH RESPECT TO THE ENVIRONMENTAL CONDITION OF THE PREMISES, INCLUDING ANY WARRANTY OR REPRESENTATION AS TO FITNESS OF THE PREMISES FOR ANY PARTICULAR USE OR PURPOSE, AS TO THE PRESENCE OR ABSENCE OF ANY HAZARDOUS
    MATERIALS, LATENT OR PATENT, ANY ENVIRONMENTAL CONDITION, KNOWN OR UNKNOWN, OR ANY AIR, SOIL, SOIL GAS, OR GROUNDWATER CONDITION, IT BEING AGREED THAT ALL RISKS AND LIABILITY INCIDENT TO ANY OF THE FOREGOING ARE TO BE BORNE BY TENANT</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant hereby represents and warrants to
    Landlord that (i) neither Tenant nor any of its legal predecessors has been required by any prior landlord, lender or governmental authority at any time to take remedial action in connection with Hazardous Materials contaminating the natural
    environment, which contamination was caused or permitted by Tenant or such predecessor or resulted from Tenant&#8217;s or such predecessor&#8217;s acts, omissions, or use or occupation of the property in question, and (ii) Tenant is not subject to any enforcement
    order issued, or regulatory proceedings or prosecution commenced, by any governmental authority in connection with the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials (including, without limitation, any order
    related to the failure to make a required reporting to any governmental authority).</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Upon prior notice and using reasonable efforts
    to coordinate with Tenant, Landlord shall have the right but not the obligation to conduct annual tests (or at any time Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>) of the Premises including, without
    limitation, intrusive tests of the subsurface soil and/or ground water, to determine whether any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation. Landlord shall pay the cost of such test of the Premises; provided,
    however, that if such tests show any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation, Tenant shall pay the cost of such test. In connection with such testing, upon the request of Landlord, Tenant shall deliver to
    Landlord or its consultant such non-proprietary information concerning the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials in or about the Premises by Tenant or any Tenant Party as Landlord may reasonably
    request. If Contamination has occurred for which Tenant is liable under this Section 3.3, Tenant shall pay all costs to conduct such tests. Tenant shall, at its sole cost and expense, promptly and satisfactorily remediate any Contamination identified
    by such testing in accordance with all Environmental Laws. Landlord&#8217;s receipt of or satisfaction with any environmental assessment in no way waives any rights that Landlord may have against Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Furthermore, upon the expiration of the Term
    or earlier termination of Tenant&#8217;s right of possession, Tenant shall surrender the Premises to Landlord free of Hazardous Materials brought upon, kept, used, stored, handled, treated, generated in, or released or disposed of from, the Premises by any
    person other than Landlord (collectively, &#8220;<b>Tenant&#8217;s Hazardous Materials</b>&#8221;) and released of any license, clearance or other authorization or requirement of any kind required to enter into and restore the Premises issued by any governmental
    authority having jurisdiction over the use, storage, handling, treatment, generation, release, disposal, removal or remediation of Hazardous Materials in, on or about the Premises (collectively referred to herein as &#8220;<b>Hazardous Materials Clearances</b>&#8221;).








    At least three (3) months prior to the surrender of the Premises or such earlier date as Tenant may elect to cease operations at the Premises, Tenant shall deliver to Landlord a narrative description of the actions proposed (or required by any
    governmental authority) to be taken by Tenant in order to surrender the Premises (including any Alterations permitted by Landlord to remain in the Premises) at the expiration or earlier termination of the Term, free from any residual impact from
    Tenant&#8217;s Hazardous Materials and otherwise released for unrestricted use and occupancy (the &#8220;<b>Surrender Plan</b>"). Such Surrender Plan shall be accompanied by a current listing of (i) all Hazardous Materials licenses and permits held by or on behalf
    of any Tenant Party with respect to the Premises, and (ii) all Hazardous Materials used, stored, handled, treated, generated, released or disposed of from the Premises, and shall be subject to the review and reasonable approval of Landlord&#8217;s
    environmental consultant. In connection with the review and approval of the Surrender Plan, upon the request of Landlord, Tenant shall deliver to Landlord or its consultant such additional non-proprietary information concerning Tenant&#8217;s Hazardous
    Materials as Landlord shall reasonably request. On or before such surrender, Tenant shall deliver to Landlord evidence that the approved Surrender Plan shall have been satisfactorily completed and Landlord shall have the right, subject to reimbursement
    at Tenant&#8217;s expense as set forth below, to cause Landlord&#8217;s environmental consultant to inspect the Premises and perform such additional procedures, including without limitation intrusive subsurface testing of soil and/or ground water, as may
    reasonably be deemed necessary to confirm that the Premises are, as of the effective date of such surrender or early termination of the Lease, free from any Tenant&#8217;s Hazardous Materials. Tenant shall reimburse Landlord, as Additional Rent, for the
    actual out-of-pocket expense incurred by Landlord for Landlord&#8217;s environmental consultant to review the Surrender Plan and to visit the Premises and verify satisfactory completion of the same, which cost shall not exceed $5,000 (which amount shall be
    increased by the same percentage as the Index as of each Adjustment Date). Landlord shall have the unrestricted right to deliver such Surrender Plan and any report by Landlord&#8217;s environmental consultant with respect to the surrender of the Premises to
    third parties on a need-to-know basis.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>If Tenant shall fail to prepare or submit a
    Surrender Plan approved by Landlord, or if Tenant shall fail to complete the approved Surrender Plan, or if such Surrender Plan, whether or not approved by Landlord, shall fail to adequately address any Tenant&#8217;s Hazardous Materials in, on or about the
    Premises, Landlord shall have the right to take such actions as Landlord may reasonably deem appropriate to assure that the Premises are surrendered free from any Tenant&#8217;s Hazardous Materials, the cost of which actions shall be reimbursed by Tenant as
    Additional Rent.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.10<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>Tenant&#8217;s obligations under this Section 3.3 shall
    survive the expiration or earlier termination of the Lease. During any period of time after the expiration or earlier termination of this Lease required by Tenant or Landlord to complete the removal from the Premises of any Hazardous Materials
    (including, without limitation, the release and termination of any licenses or permits restricting the use of the Premises and the completion of the approved Surrender Plan), Tenant shall continue to pay the full Rent in accordance with this Lease for
    any portion of the Premises not relet by Landlord in Landlord&#8217;s sole discretion, which Rent shall be prorated daily.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">3.4</td>
        <td style="text-align: justify"><u>Alterations</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Consent</u>. Tenant may make any alterations,
    improvements, additions or changes to the Premises (collectively &#8220;Alterations&#8221;) that meet all of the following criteria without first obtaining Landlord&#8217;s Consent: (a) the Alterations are cosmetic, (b) the Alterations are non-structural and do not
    affect the mechanical systems of the Building, (c) the Alterations cost less than $1,000,000.00 per project (which amount shall be increased by the same percentage as the Index as of each Adjustment Date); and (d) after the Alterations, the Premises
    will continue to be used for the Permitted Use (collectively, Alterations meeting the criteria of (a)-(d), &#8220;Minor Alterations&#8221;). Any Alterations that are not Minor Alterations shall be subject to Landlord&#8217;s approval, such approval not to be
    unreasonably withheld, conditioned or delayed. Tenant shall reimburse Landlord for any third-party expenses reasonably incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s plans for Alterations and Tenant&#8217;s
    performance thereof. Notwithstanding the foregoing, Tenant shall have the right to construct the renovation of the conference center located at 2850 Gazelle Court (the &#8220;Conference Center Alterations&#8221;), at Tenant&#8217;s sole cost and expense, in accordance
    with the plans and specifications identified on <u>Exhibit H</u> attached hereto (the &#8220;CCA Plans&#8221;) and in accordance with all Applicable Laws, provided any modifications to the plans for the Conference Center Alterations that are not Minor
    Alterations, minor field work changes not requiring Tenant&#8217;s approval under the applicable construction contract for such Alterations, or changes that are required to comply with applicable law, shall require, in each case, Landlord&#8217;s approval, not to
    be unreasonably withheld, conditioned or delayed, and the Conference Center Alterations shall otherwise comply with this Section 3.4. Tenant hereby agrees to provide copies of all plans of such Alterations, regardless of whether Landlord&#8217;s consent is
    required. Tenant shall diligently and expeditiously complete any Alterations commenced. All Alterations shall become part of the realty constituting the Premises and shall belong to Landlord and shall not be removed by Tenant. If any Alteration (other
    than the Conference Center Alterations) is anticipated to cost more than $1,500,000, Landlord shall have the right to require Tenant to post a performance or payment bond in connection with any work or service done or purportedly done by or for the
    benefit of Tenant. Tenant acknowledges and agrees that all such work or service is being performed for the sole benefit of Tenant and not for the benefit of Landlord. Landlord shall, at the time it provides its approval for a proposed Alteration,
    advise Tenant whether the Alteration, or any portion thereof, is a Required Removable, as defined in Section 4.2.2.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.2 &#160;&#160;&#160;&#160;&#160;&#160;<u>Liens</u>. With respect to any Alterations, Tenant hereby agrees as follows: (a) Tenant shall not cause or
    permit any construction, mechanics&#8217; or other liens or encumbrances to be placed upon the Premises, or Tenant&#8217;s leasehold interest hereunder, whether in connection with any work or service done or purportedly done by or for the benefit of Tenant, its
    subtenants, or any other party acting under or through Tenant, or otherwise, (b) Tenant shall cause all Alterations to be constructed free of all liens, in accordance with all Applicable Laws and shall, upon Landlord&#8217;s request, deliver lien waivers to
    Landlord in the form required by Applicable Law, (c) Tenant shall pay the costs of the Alterations and so that Landlord, the Premises will be protected against any loss from any mechanic&#8217;s, materialmen&#8217;s, or other liens, and (d) prior to the
    commencement of the construction of any Alterations, Tenant shall give to Landlord evidence of the insurance required by <u>Section 6.2.4</u>. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant may contest any lien if (i)
    such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord of such dispute, and (iii) such lien is fully bonded by Tenant to the reasonable satisfaction of Landlord and
    any Mortgagee. Tenant shall give Landlord notice at least fifteen (15) days prior to the commencement of any work in the Premises, other than any Alterations that are purely cosmetic.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requirements</u>. Prior to starting work on
    any Alterations, Tenant shall furnish Landlord with two (2) complete sets of professionally prepared working drawings (which shall include any architectural, structural, electrical, mechanical, computer system wiring, and telecommunication plans, which
    shall all be in CAD or other electronic format if requested by Landlord), and will be consistent with the construction methods and procedures manual attached hereto as Exhibit K, as amended from time to time for the Premises (the &#8220;<b>Tenant
      Construction Manual</b>&#8221;); names of contractors reasonably acceptable to Landlord; required permits and approvals; and evidence of contractor&#8217;s and subcontractor&#8217;s insurance in amounts reasonably required by Landlord and naming as additional insureds
    the Landlord, the managing agent for the Premises, and such other Additional Insured Parties (as defined in Section 13) as Landlord may designate for such purposes. All Cable shall be clearly marked with adhesive plastic labels (or plastic tags
    attached to such Cable with wire) to show the purpose of such Cable (i) every six (6) feet in locations behind walls, beneath floors, and above ceilings (specifically including, but not limited to, the electrical room risers), and (ii) at the
    termination point(s) of such Cable. &#8220;<b>Cable</b>&#8221; shall mean and refer to any electronic, fiber, phone and data cabling and related equipment that is installed by or for the exclusive benefit of Tenant or any party acting under or through Tenant. Any
    changes to the plans and specifications, other than di minimus changes that are purely cosmetic, do not affect the Building structure or mechanical systems, and do not cause the cost of the Alterations to exceed $1,000,000 (which amount shall be
    increased by the same percentage as the Index as of each Adjustment Date), must also be submitted to Landlord for its approval. Prior to commencing Alterations, Tenant shall provide Landlord with a copy of the contract for the Alterations and evidence
    satisfactory to Landlord as to the existence of all necessary permits (to the extent not previously provided). Alterations shall be (a) constructed in a good and workmanlike manner, (b) consistent with first class standards, (c) consist of materials of
    a quality reasonably approved by Landlord, and Tenant shall ensure that no Alteration impairs any Building system, (d) performed by contractors or mechanics whose labor union affiliations are not incompatible with those of any workers, contractors or
    subcontractors who may be employed, retained or engaged by the Landlord for the development and making of any alterations at the Premises, and who are otherwise reasonably approved by Landlord, (e) in accordance with the Tenant Construction Manual, if
    any, and (f) designed and performed in accordance with all applicable Laws. It shall be deemed reasonable for Landlord to withhold its consent to any Alteration that adversely affects a Building&#8217;s roof, structure, or systems, that is inconsistent with
    a first-class life science building, that results in an increase in gross floor area at the Premises or alteration of any Building footprint, that would violate any certificate of occupancy for the Buildings or any other permits or licenses relating to
    the Buildings, that would reduce the utility of the Premises for life sciences laboratory, research, and manufacturing purposes, or that is otherwise inconsistent with the requirements of this Section. Tenant shall reimburse Landlord for any
    third-party expenses incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s plans for Alterations and Tenant&#8217;s performance thereof. Upon completion, Tenant shall furnish &#8220;as-built&#8221; plans (in CAD or other electronic
    format, if requested by Landlord) for Alterations, customary American Institute of Architects completion affidavits, full and final waivers of lien, any applicable certificate of occupancy for the space affected by such Alterations and other applicable
    municipal or local sign-offs and inspection reports, and any other items reasonably required by Landlord for closing out the particular work in question. Landlord&#8217;s approval of an Alteration shall not be deemed to be a representation by Landlord that
    the Alteration complies with Law or will not adversely affect any Building system.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Construction Oversight Fee</u>. With respect
    to any Alterations requiring Landlord&#8217;s consent under Section 3.4.1, Tenant shall pay Landlord a construction oversight fee (&#8220;<b>Construction Oversight Fee</b>&#8221;) equal to the sum of one percent (1%) of total hard and soft project costs, provided that
    Landlord&#8217;s obligations in connection with the Alterations are limited to oversight only and not direct management of the project. The Construction Oversight Fee shall be calculated based on hard and soft project costs for the Alterations that were
    approved by Landlord for the portion of work that has been performed and invoiced and shall be payable monthly in arrears concurrent with the approved hard and soft project costs for the Alterations during the applicable month.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Completion</u>. Upon the completion of any
    Alterations, Tenant shall, to the extent applicable, promptly give to Landlord (a) a reproducible copy of the &#8220;as-built&#8221; drawings of such Alterations, (b) a certificate of completion executed on behalf of Tenant&#8217;s architect and/or engineering
    certifying completion of such Alterations in accordance with the respective plans and specifications, (c) a copy of the certificate of occupancy issued by the applicable governmental authorities with respect to such Alterations, and (d) copies of any
    warranties or guarantees with respect to such Alterations (and ensure that such warranties or guarantees are assignable to Landlord and/or run to both Landlord and Tenant&#8217;s benefit).</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">3.4.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Ownership of Alterations</u>. Any Alterations
    shall belong to Tenant until the Termination Date, at which time the Alterations (other than Tenant&#8217;s Trade Fixtures (as hereinafter defined)) shall belong to Landlord; provided, however, in no event shall the Alterations be removed by Tenant prior to
    the Termination Date, except as expressly provided herein. For purposes of this Lease, &#8220;<b>Trade Fixtures</b>&#8221; shall mean a piece of equipment placed on the Premises owned by Tenant and used in Tenant&#8217;s trade or business. For the avoidance of doubt,
    Trade Fixtures shall not include, without limitation, Building systems and machinery, built-in cabinet work and/or lab benches, purpose-built mezzanine space, all HVAC, air handling, electrical, mechanical and plumbing equipment and related ducts,
    shafts, and conduits, all exterior venting fume hoods, walk-in freezers and refrigerators, clean-rooms, climatized rooms, electrical panels and power back-up distribution systems. The parties agree that Landlord will be treated for all purposes,
    including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other cost recovery deductions for federal tax purposes with respect to) any improvements, equipment, or personal property that were paid for, or
    reimbursed by, Landlord, including any allowance provided by Landlord, and Tenant will be treated for all purposes, including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other cost recovery deductions for
    federal tax purposes with respect to) any improvements to the extent that the cost for such improvements were paid for by Tenant and to the extent any such costs exceed any allowance provided by Landlord. Unless required to adopt a contrary position as
    a result of an administrative or judicial proceeding, the parties shall take no action inconsistent with, the intentions set forth in this paragraph. The parties will provide each other with such cooperation as is reasonably necessary to implement the
    intentions of this paragraph.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Jeopardy of Insurance</u>. Tenant shall
    neither do nor omit to do anything that might result in the actual or threatened reduction or cancellation of or material adverse change in insurance carried by Landlord or Tenant on the Premises. If any such insurance is actually, or threatened to be,
    cancelled, reduced or materially adversely changed by an insurer as a result of the use or occupancy of the Premises or any article kept in or about the Premises or any act or omission of Tenant or any person for whom Tenant is in law responsible or
    any occupant of the Premises, and if Tenant fails to remedy the condition or the use or occupancy giving rise to such actual or threatened cancellation, reduction or change within three (3) business days after notice thereof, Landlord may, without
    limiting its other remedies for the default, enter upon the Premises and remedy the condition, use or occupancy giving rise to such actual or threatened cancellation, reduction or change, and Tenant shall pay to Landlord its cost of doing so within ten
    (10) days following invoice, plus an administrative fee equal to ten percent (10%) of such cost. Landlord shall not be liable for any damage to either the Premises or any property located on the Premises as a result of such entry.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Dogs</u>. Tenant shall be permitted to
    bring a reasonable number of non-aggressive, fully domesticated, properly licensed, fully vaccinated, and well behaved dogs, kept by Tenant&#8217;s employees as pets, into the Premises, provided and upon condition that: (a) all dogs shall be strictly
    controlled at all times, (b) dogs shall not be permitted to foul, damage or otherwise mar any part of the Buildings or Premises; and (c) while entering and exiting the Premises, all dogs shall be kept on leashes. Landlord may limit the number, weight,
    and breed of dogs that may be permitted in the Premises, and Landlord may implement other rules and regulations not inconsistent with this Section 3.6 that Landlord, in its sole discretion, deems reasonable or prudent. Tenant shall be responsible for
    any damage and additional cleaning costs and all other costs which may arise from the dogs' presence in the Buildings and on the Premises. Tenant shall be liable for, and hereby agrees to indemnify, defend and hold Landlord harmless from any and all
    claims arising from any and all acts (including but not limited to biting and causing bodily injury to, or damage to the property of, another lessee, sublessee, occupant, licensee, invitee, Landlord or an employee of Landlord) of, or the presence of,
    any dog in or about the Premises or the Buildings. Tenant shall promptly remove any dog waste and excrement from the Premises and Buildings. Dogs shall be strictly controlled and supervised at all times (including, without limitation, by being on
    leashes) by Tenant&#8217;s employees, with no less than one (1) such employee responsible for so controlling and supervising no more than two (2) dogs apiece. Within three (3) business days following Landlord&#8217;s request therefor, Tenant shall provide Landlord
    with reasonably satisfactory evidence showing that all current vaccinations have been received by any dogs permitted on the Premises. No dog shall be brought to the Premises if such dog is ill or contracts a disease that could potentially threaten the
    health or wellbeing of any person on the Premises (which diseases may include, without limitation, rabies, leptospirosis and lyme disease). Tenant shall not permit any objectionable dog related noises or odors to emanate from the Premises (as
    determined by Landlord in its sole discretion), and in no event shall any dog be at the Premises overnight or for any extended period of time. Tenant shall install and maintain dog waste bag dispensers in outdoor areas of the Premises, and all waste
    generated by any dogs in or about the Premises shall be promptly removed and disposed of (on no less than a daily basis) in trash receptacles. Any areas of the Premises affected by such waste shall be immediately cleaned and otherwise sanitized.
    Landlord may require Tenant to permanently ban any dog from the Premises if (i) any such dog exhibits aggressive behavior, damages or destroys property in the Premises, violates specific provisions of this Section, defecates or urinates in any
    non-outdoor area of the Project, or defecates in any outdoor area of the Project and Tenant fails to remove such waste in accordance with the terms of this Section, and (ii) any such dog is found by Landlord in its sole but good faith discretion to be
    a substantial, repeated nuisance to the Premises, and, in any such event, such substantial, repeated nuisance persists after at least two (2) written notices to Tenant from Landlord in any twelve (12) month period), then Landlord may terminate Tenant&#8217;s
    rights under this Section. Tenant shall promptly pay to Landlord, within thirty (30) days after demand, all costs incurred by Landlord that directly result from the presence of any of dogs in the Premises. Tenant&#8217;s right provided in this Section is
    personal only to the original named Tenant and/or any Permitted Transferee, shall not be exercisable by any other assignee, subtenant or other transferee of or successor to any portion of Tenant&#8217;s interest under the Lease or to the Premises.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>LEED Standards</u>. Tenant shall ensure
    that the Buildings meet at least the standard for a &#8220;Gold&#8221; rating under the U.S. Green Building Council&#8217;s Leadership in Energy and Environmental Design (&#8220;<b>LEED</b>&#8221;) rating system for a campus consisting of multiple buildings. In connection with the
    foregoing, Tenant shall reasonably cooperate with Landlord in its submission of all filings to obtain and maintain Gold or better LEED rating for the Buildings as a campus. Tenant shall reimburse Landlord for the costs to obtain and maintain such Gold
    or better LEED rating for the Buildings as a campus in an amount not to exceed in the aggregate more than $40,000.00 annually, including any discounts and credit that may be applied to reduce such costs. Tenant shall not be responsible for any costs to
    obtain LEED Gold or better certification for the Conference Center, individually, in connection with the campus designation of the Buildings (it being acknowledged that Tenant&#8217;s sole obligation with respect to the Conference Center Alterations, as
    shown in the CCA Plans, will be to meet the applicable California State and local standards for energy efficiency and environmental design). All Alterations, and any lighting installed by Tenant in the Premises, shall be designed, maintained, and
    installed in accordance with the requirements for LEED Gold or better campus certification, as the same may change from time to time If necessary to ensure compliance with the applicable LEED standards, Tenant further agrees to engage a qualified third
    party LEED or Green Globe Accredited Professional or similarly qualified professional during the design phase of any Alterations, in order to review all plans, material procurement, demolition, construction and waste management procedures to ensure
    they are in full conformance with the requirements to maintain the applicable LEED rating.</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 4</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>REPAIR AND MAINTENANCE; SERVICES</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">4.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant Repair and Maintenance Obligations</u>.
    The parties intend for this Lease to be absolutely triple net. Tenant shall be responsible for all repairs, replacements and maintenance of the Premises. Landlord shall have no obligation whatsoever to repair or maintain the Premises. Tenant shall
    repair and maintain the Premises in substantially the condition as exists as of the Effective Date of this Lease (and as it may be improved or altered thereafter), keep same in good order, condition and repair, and in compliance with Applicable Laws,
    ordinary wear and tear and casualty excepted, to the extent Tenant is not otherwise obligated to restore the same.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">4.2</td>
        <td style="text-align: justify"><u>Condition of Premises on Surrender</u></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">4.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except as otherwise provided in this <u>Section
      4.2</u>, upon the Termination Date, all Alterations (other than Tenant&#8217;s Trade Fixtures) shall belong to Landlord without compensation, and title shall pass to Landlord under this Lease. On the Termination Date, Tenant shall give Landlord possession
    of the Premises, together with all such Alterations (other than Tenant&#8217;s Trade Fixtures), in the good, broom clean condition, free of all debris, excepting only ordinary wear and tear and damage that Tenant is not required to repair or restore under
    this Lease. On or prior to the Termination Date, Tenant shall also (a) remove all of Tenant&#8217;s furniture, Trade Fixtures, furnishings, equipment belonging to the Tenant, and other personal property (collectively, the &#8220;<b>Personalty</b>&#8221;), and (b) repair
    any damage caused by the removal of such Personalty. All of Tenant&#8217;s Personalty not so removed by Tenant, may be removed from the Premises by Landlord and stored, at Tenant&#8217;s sole risk and expense, and in any event, Landlord shall not be responsible
    for the value, preservation, or safekeeping thereof. Tenant shall pay to Landlord, upon demand, all reasonable expenses so incurred by Landlord, including the cost of repairing any damage caused by removal and storing such Personalty (collectively, &#8220;<b>Tenant&#8217;s








      Property</b>&#8221;). Any such Tenant&#8217;s Property not claimed by Tenant within sixty (60) days after Tenant&#8217;s surrender of the Premises shall, at Landlord&#8217;s option, be deemed either abandoned or conveyed by Tenant to Landlord under this Lease without
    further payment or credit by Landlord to Tenant. On the Termination Date, Tenant shall assign to Landlord all manufacturers&#8217; and contractors&#8217; warranties with respect to the Premises and the Alterations (including all fixtures therein or thereon but
    excluding Tenant&#8217;s Trade Fixtures) and Tenant shall use commercially reasonable efforts obtain the consent of the issuers of such warranties (which may include, without limitation, the payment of an assignment fee), to the extent that such consent is
    required for the assignment to Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">4.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord, at the time required by <u>Section
      3.4.1</u>, by written notice to Tenant may require Tenant, at Tenant&#8217;s expense, to remove any Alterations or other affixed installations that, in Landlord&#8217;s reasonable judgment, are of a nature that are not customary office or life science
    improvements and would require removal and repair costs that are materially in excess of the removal and repair costs associated with standard improvements for the Permitted Use (&#8220;<b>Required Removables</b>&#8221;). Required Removables shall include, without
    limitation, internal stairways, raised floors, vaults, rolling file systems, structural alterations and modifications (including any slab penetrations) other than de minimis alterations and modifications associated with connection of other improvements
    to the structure of the Building or relocation of demising walls provided that the same are otherwise consistent with first class life science buildings, Tenant&#8217;s signage, supplemental systems (including HVAC), vivariums, and any Cable installed by or
    on behalf of Tenant that is not necessary for the proper functioning of any Alterations remaining in the Premises in accordance with this Lease. Notwithstanding the foregoing, any fixtures or improvements existing within the Premises on the Effective
    Date, or as shown on the CCA Plans, shall not be deemed Required Removables. The Required Removables shall be removed by Tenant before the expiration or earlier termination of this Lease in accordance with Section this Section 4.2, unless otherwise
    directed by Landlord. Landlord shall be treated as the owner of all Alterations (but, subject to Section 4.2.1, not any of Tenant&#8217;s Property, including any trade fixtures and equipment that are installed in a manner that will not damage the Premises
    when removed) during the term of the Lease, including for tax and depreciation purposes, but Tenant shall have the exclusive right to use the same subject to the terms of this Lease.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">4.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Services and Utilities</u>. Landlord
    shall not be obligated to furnish to the Premises any services or utilities (including, without limitation, janitorial services), and Tenant shall contract directly with the providers of all services and utilities Tenant desires to receive at the
    Premises, at Tenant&#8217;s sole cost and expense. Tenant shall have the right to add alternative electricity sources such as additional solar panels, the installation of which shall be subject to Section 3.4. Landlord is not responsible for the furnishing
    of, or any interruption, diminishment or termination of, services or utilities, whether due to the application of Laws, the failure of any equipment, the performance of maintenance, repairs, improvements or alterations, or utility interruptions, and no
    such interruption, diminishment, or termination shall render Landlord liable to Tenant, give rise to an abatement of Rent, or relieve Tenant from the obligation to fulfill any covenant or agreement. Except as expressly set forth in Article 9, below,
    Landlord shall in no event be required under any provision of this Lease or applicable Law to maintain or repair or to make any alterations, rebuildings, replacements, changes, additions or improvements on or off the Premises during the Term of this
    Lease. Tenant acknowledges that it shall be responsible for providing and procuring all other services necessary to its operations in and on the Premises. If Tenant (or any party claiming by, through or under Tenant) pays directly to the provider for
    any energy consumed at the Buildings, Tenant, promptly upon request, shall deliver to Landlord (or, at Landlord&#8217;s option, execute and deliver to Landlord an instrument enabling Landlord to obtain from such provider) any data about consumption that
    Landlord, in its reasonable judgment, is required to disclose to a prospective buyer, tenant or mortgage lender under California Public Resources Code &#167;25402.10 or any similar law. Further, Tenant hereby waives and releases its right to make repairs at
    Landlord&#8217;s expense under Sections 1932(1), 1933(4), 1941 and 1942 of the California Civil Code or any similar or successor laws now or hereinafter in effect. At Landlord&#8217;s request, Tenant shall provide Landlord information regarding Tenant&#8217;s energy
    usage at the Premises from time to time (provided that Landlord shall hold such information confidential to the extent Landlord is not required to disclose such information pursuant to Applicable Law, nothing in this sentence being deemed to prohibit
    Landlord from utilizing such information to make public statements about the sustainability profile or &#8220;green&#8221; nature of Landlord, or Landlord&#8217;s affiliates, properties).</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 5<br>
    ASSIGNMENT AND SUBLETTING</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 63.45pt">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">5.1</td>
        <td style="text-align: justify"><u>General Prohibition on Transfers</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Transfers Generally</u>. Tenant shall not,
    directly or indirectly, make a Transfer (as defined below), without Landlord&#8217;s consent, except as expressly set forth in this <u>Article 5</u>, and any purported Transfer that does not comply with the provisions of this <u>Article 5</u> shall, at
    Landlord&#8217;s option, be deemed an Event of Default by Tenant and shall be voidable by Landlord. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or successor laws, now or hereinafter in effect, and all
    other remedies, including any right at law or equity to terminate this Lease in connection with Landlord&#8217;s withholding its consent to any Transfer, on its own behalf and on behalf of the proposed transferee. Landlord shall not unreasonably withhold,
    condition, or delay its consent to an assignment of this Lease or any sublet of the Premises, subject to the terms and conditions of this Article 5. Without limitation, it is agreed that Landlord&#8217;s consent shall not be considered unreasonably withheld
    if the proposed Transferee (defined below) (a) is a governmental entity, (b) is incompatible with the character of occupancy of a first class life sciences buildings, (c) is an entity with which the payment for the sublease or assignment is determined
    in whole or in part based upon its net income or profits, (d) would subject the Premises to a use that would: (i) involve increased personnel or wear upon the Buildings in a manner inconsistent with first-class life science buildings; (ii) require any
    addition to or material modification of the Premises or the Buildings in order to comply with building code or other governmental requirements; or (iii) involve a violation of the Permitted Use clauses of this Lease, or (e) if there is any other
    reasonable ground not stated above for withholding consent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Clients and Business
      Partners</b>&#8221; means persons or entities who are not employees or agents of Tenant or its Affiliates but are occupying or using portions of the Premises and are either (i) performing services for Tenant as subcontractors under Tenant's contracts, (ii)
    personnel employed by persons or entities for whom Tenant is performing services on a contractual basis, or (iii) personnel employed by persons or entities with whom Tenant is engaged in a joint venture or joint teaming effort.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Office Sharing</b>&#8221;
    means the use of portions of the Premises by Clients and Business Partners, if, with respect to such Clients and Business Partners, such use is in connection with the services being provided to Tenant by the applicable Clients and Business Partners,
    the services being provided to the applicable Clients and Business Partners by Tenant, or the services being jointly provided by Tenant and the applicable Clients and Business Partners.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Transfer</b>&#8221; means any
    assignment, pledge, mortgage, charge, debenture (floating or otherwise), hypothecation, encumbrance, lien attaching to, collateral assignment, or other transfer of this Lease or the leasehold created hereby, or any sublet or other transfer of any
    portion of the Premises, or any Interest Transfer (as defined below), in any case whether voluntarily, by operation of law, or otherwise, or permitting the Premises to be used or occupied by anyone other than Tenant.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Transferee</b>&#8221; means the party to which a Transfer is made.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Interest Transfer</b>&#8221;
    means if Tenant is a corporation, trust, partnership, limited liability company or other entity, (i) the transfer of a Controlling Interest or a majority of the voting stock, beneficial interest, partnership interests, membership interests or other
    ownership interests therein (whether at one time or in the aggregate) or (ii) the sale, mortgage, hypothecation, or pledge of more than 50% of Tenant&#8217;s net assets. A &#8220;<b>Controlling Interest</b>&#8221; means the effective control over the management of such
    entity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Consent Requests</u>. If Tenant desires to
    effect a Transfer and such Transfer requires Landlord&#8217;s consent, then Tenant shall give to Landlord Notice thereof at least thirty (30) days, but not more than sixty (60) days, prior to the proposed effective date of the Transfer, which Notice shall
    include (a) the name and address of the proposed Transferee, (b) the relevant terms of the Transfer, (c) copies of financial reports and other relevant financial information for the proposed Transferee, (d) information regarding the nature of the
    business the proposed Transferee intends to operate in the Premises and how long the proposed Transferee has operated such business, (e) a fully executed copy of the proposed assignment, sublease, or other document to be used to effect the Transfer
    (the &#8220;<b>Transfer Document</b>&#8221;), and (f) payment to Landlord of One Thousand and No/100 Dollars ($1,000.00) as a transfer review fee. In addition, Tenant shall reimburse Landlord for any third-party expenses reasonably incurred by Landlord in
    connection with the review, inspection, and coordination of Tenant&#8217;s request for Landlord&#8217;s consent to a Transfer, not to exceed $5,000 per request (which amount shall be increased by the same percentage as the Index as of each Adjustment Date).
    Landlord shall not unreasonably withhold, condition or delay its consent to a Transfer. If Landlord&#8217;s consent is required with respect to a Transfer, and Landlord fails to respond to Tenant&#8217;s request for consent within thirty (30) days of Tenant&#8217;s
    request and submission of the documents required by this Section 5.1.2, Tenant may send a second written request, which request shall contain, in bold, capital letters, the following: &#8220;THIS NOTICE CONSTITUTES TENANT&#8217;S SECOND NOTICE OF ITS REQUEST FOR
    CONSENT TO A TRANSFER PURSUANT TO SECTION 5.1.2 OF THE LEASE; LANDLORD&#8217;S FAILURE TO RESPOND TO THIS NOTICE WITHIN FIVE (5) BUSINESS DAYS SHALL BE DEEMED LANDLORD&#8217;S CONSENT TO THE REQUESTED TRANSFER.&#8221; If Landlord fails to respond to such second notice
    within five (5) business days of receipt, Tenant&#8217;s request for the applicable Transfer shall be deemed approved. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or successor laws, now or hereinafter
    in effect, and all other remedies, including, without limitation, any right at law or in equity to terminate this Lease, on its own behalf and, to the extent permitted under all Applicable Laws, on behalf of the proposed transferee.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Permitted Transfer</u>. Notwithstanding
    anything in this <u>Article 5</u> to the contrary, Tenant may assign its interest in this Lease or sublease all or any part of the Premises (each a &#8220;<b>Permitted Transfer</b>&#8221;) to a Permitted Transferee (defined below) with notice to Landlord
    (delivered prior to the Transfer, or in the event Tenant is prohibited from doing so by Applicable Laws or contractual obligations, then as soon as reasonably practical) but without Landlord&#8217;s prior written consent; provided, that (i) with respect to a
    Permitted Transfer involving an assignment of this Lease, the Permitted Transferee assumes this Lease by a written assumption agreement delivered to Landlord prior to the effective date of such Permitted Transfer (unless such prior delivery is
    prohibited by Applicable Laws, in which event Tenant shall deliver such assumption agreement as soon as allowed), (ii) the Permitted Transferee shall use the Premises only for the Permitted Use, (iii) the use of the Premises by the Permitted Transferee
    shall not violate any other agreements or leases affecting the Property, (iv) the occurrence of a Permitted Transfer shall not waive Landlord&#8217;s rights as to any subsequent Transfer, (v) the Permitted Transferee shall satisfy the Credit Requirement
    (defined below), and (vi) Tenant shall have given Landlord written notice at least thirty (30) day before such Transfer (unless such notice is prohibited by applicable Law, in which event Tenant shall give such notice within ten days following such
    Transfer). As used herein, (A) &#8220;<b>Affiliate</b>&#8221; means any person or entity who or which controls, is controlled by, or is under common control with Tenant, (ii) a corporation or other entity which shall be a wholly owned subsidiary of the Tenant,
    (iii) the parent corporation or other entity that wholly owns Tenant, or (iv) a subsidiary of such parent corporation or other entity that wholly owns Tenant, or a corporation or other entity having a majority of its ownership in common with the
    ownership of Tenant, or (v) a Successor corporation, limited liability company or other entity; (B) &#8220;<b>Successor</b>&#8221; means any (i) business entity in which or with which Tenant is merged or consolidated in accordance with applicable statutory
    provisions governing merger and consolidation of business entities, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor, or (ii) the successor or surviving corporation or other entity in the event of a merger or consolidation
    of the Tenant with another corporation, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor; (C) &#8220;<b>Purchaser</b>&#8221; means any person or entity who or which acquires all or substantially all of the assets or equity interests of
    Tenant; (D) &#8220;<b>Permitted Transferee</b>&#8221; means an Affiliate, Successor or Purchaser. The &#8220;<b>Credit Requirement</b>&#8221; shall be deemed satisfied if, as of the effective date of the Permitted Transfer, the resulting tenant under this Lease meets or
    exceeds all of following minimum criteria immediately following the Transfer: (i) cash on hand equal to at least Two Billion Dollars ($2,000,000,000) according to the Permitted Transferee&#8217;s most recent financial statement, determined in accordance with
    generally accepted accounting principles (&#8220;<b>GAAP</b>&#8221;), (ii) outstanding debt of not more than sixty (60%) of the Permitted Transferee&#8217;s available cash on hand (as determined pursuant to the foregoing subsection (i) according to the Permitted
    Transferee&#8217;s most recent financial statement, determined in accordance with GAAP, and (iii) a market capitalization equal to at least Five Billion Three Hundred Million Dollars ($5,300,000,000).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">5.2</td>
        <td style="text-align: justify"><u>Other Permitted Transfers</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Office Sharing</u>. Notwithstanding anything
    in this <u>Article 5</u> to the contrary, provided no Event of Default has occurred and is continuing, Tenant may, without Landlord&#8217;s consent but upon at least ten (10) days&#8217; prior notice to Landlord, permit up to ten percent (10%) of the total
    leasable area of the Premises to be used for Office Sharing by Clients and Business Partners, without the same constituting a Transfer. Tenant agrees to notify Landlord, promptly upon Landlord&#8217;s written request therefor, as to the approximate amount of
    Office Sharing by Clients and Business Partners and to certify to Landlord that such use or occupancy constitutes Office Sharing by Clients and Business Partners and does not constitute a sublease, assignment or other leasehold interest.
    Notwithstanding the foregoing, Tenant shall not have the right to engage in Office Sharing with respect to any particular Clients and Business Partners as aforesaid if such Clients and Business Partners are engaged in a business, or the Premises will
    be used in a manner, that is inconsistent with the Permitted Use. For purposes of this Lease, the acts or omissions of the employees or other personnel of Clients and Business Partners shall be deemed to be the acts or omissions (as applicable) of
    Tenant. Upon Landlord&#8217;s request, Clients and Business Partners who are Office Sharing shall provide to Landlord satisfactory evidence of insurance covering their activities within the Premises.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">5.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Non-Transfers</u>. For so long as Tenant
    is a corporation whose ownership equity is available through the free trade of shares of stock on nationally recognized stock exchanges or over-the-counter (OTC) markets that are subject to the oversight of the United States Securities and Exchange
    Commission (a &#8220;<b>Public Company</b>&#8221;), any transfer of Tenant&#8217;s equity interests (or those of its Affiliates) whatsoever shall not be deemed a Transfer under this Lease and, for the avoidance of doubt, shall not require Landlord&#8217;s consent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">5.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Conditions to Effectiveness</u>. As
    conditions precedent to any Transfer becoming effective and binding on Landlord:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.4.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>except as otherwise specified herein, prior to
    the proposed effective date of the Transfer, Tenant shall give to Landlord a copy of the fully executed Transfer Document, which shall (i) be in form and substance reasonably acceptable to Landlord, and (ii) for an assignment of this Lease, contain
    Transferee&#8217;s express assumption of Tenant&#8217;s obligations under this Lease and waivers by Tenant, for the benefit of Landlord, of all applicable suretyship defenses (unless such prior delivery is prohibited by Applicable Laws, in which event Tenant shall
    deliver such documents as soon as allowed); and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; as of the proposed effective date of the Transfer, there shall exist no Event of Default.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">5.5</td>
        <td style="text-align: justify"><u>Miscellaneous</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Notwithstanding any Transfer, permitted or
    otherwise, including without limitation a Permitted Transfer, (a) Tenant shall not be released and shall at all times remain directly, primarily, and fully responsible and liable for the payment of Rent and for compliance with all of the other
    obligations to be performed by Tenant under the terms, provisions and covenants of this Lease, and (b) if any Transferee defaults under this Lease, then Landlord may proceed directly against Tenant without the necessity of exhausting remedies against
    such Transferee. Notwithstanding the foregoing, Tenant shall be automatically released from all liability under the Lease accruing from and after the date of a Transfer if the Transfer is a Permitted Transfer that is a merger or consolidation whereby
    the named Tenant herein is not the surviving entity; provided, however, as conditions of the foregoing release: (i) the surviving entity shall assume, either expressly or by operation of law, all of the obligations of the preceding entity for
    liabilities accruing before and after the Transfer, and (ii) the surviving entity must retain ownership of substantially all of the assets of the preceding entity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Upon the occurrence of an Event of Default, if
    all or any portion of the Premises is then subject to one or more subleases, then Landlord, in addition to any other remedies provided in this Lease or at law or in equity, may collect directly from the subtenants under such subleases all rents due and
    becoming due to Tenant or a Transferee under such subleases and apply such rent against any sums due to Landlord from Tenant under this Lease, and no such collection shall be construed to constitute a novation or release of Tenant from the further
    performance of Tenant&#8217;s obligations under this Lease.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">27</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except for any Permitted Transfer, if the
    proposed Transfer is an assignment or a sublease of more than seventy five percent (75%) of the Premises for a term longer than seventy five percent (75%) of the then remaining Term, then Landlord shall have the right in its sole and absolute
    discretion to terminate this Lease by sending Tenant written notice of such termination within thirty (30) days after Landlord's receipt of Tenant's notice requesting consent to the Transfer. If Landlord elects to terminate this Lease, Tenant may
    withdraw its notice requesting consent to the Transfer by providing written notice within five (5) business days after Landlord&#8217;s termination (with time being of the essence), in which case Landlord&#8217;s termination shall be negated, and the Lease shall
    continue pursuant to its terms. If Landlord elects to terminate this Lease, then Tenant shall tender the Premises to Landlord in the condition required by this Lease at the end of the Term, and this Lease shall terminate, on the proposed effective date
    of the requested Transfer, and Tenant shall have no further obligations under this Lease except for those accruing prior to the termination date and those that, pursuant to the terms of the Lease, survive the expiration or early termination of the
    Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except for a Permitted Transfer, in the event,
    if any, that (i) all rent and other consideration that Tenant receives as a result of a Transfer exceeds (ii) the Rent payable to Landlord for the portion of the Premises and Term covered by the Transfer (allocated on a per square foot basis), then
    Tenant shall, at Landlord&#8217;s election, pay to Landlord an amount equal to fifty percent (50%) of such excess, from time to time on a monthly basis upon Tenant&#8217;s receipt of such excess; provided that in determining any such excess, Tenant may deduct from
    the excess all reasonable and customary expenses directly incurred by Tenant in connection with such Transfer, except that any construction costs incurred by Tenant in connection with such Transfer shall be deducted on a straight-line basis over the
    term of the applicable Transfer. If Tenant is in Default, Landlord may require that all sublease payments be made directly to Landlord, in which case Tenant shall receive a credit against Rent in the amount of Tenant&#8217;s share of payments received by
    Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Without limiting Landlord&#8217;s right to withhold
    its consent to any transfer by Tenant, and regardless of whether Landlord shall have consented to any such transfer, neither Tenant nor any other person having an interest in the possession, use or occupancy of the Premises or any part thereof shall
    enter into any lease, sublease, license, concession, assignment or other transfer or agreement for possession, use or occupancy of all or any portion of the Premises that provides for rent or other payment for such use, occupancy or utilization based,
    in whole or in part, on the net income or profits derived by any person or entity from the space so leased, used or occupied, and any such purported lease, sublease, license, concession, assignment or other transfer or agreement shall be absolutely
    void and ineffective as a conveyance of any right or interest in the possession, use or occupancy of all or any part of the Premises..</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">5.5.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; This Section 5.5 shall survive the expiration or earlier termination of this Lease.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">28</font></div>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 6<br>
    INDEMNIFICATION; RELEASE; INSURANCE</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 96.1pt">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">6.1</td>
        <td style="text-align: justify"><u>Indemnification and Release</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>To the extent permitted by Applicable Law,
    Tenant shall protect, indemnify, release, defend and hold Landlord (and the Landlord Parties) harmless from and against any and all Claims to the extent caused by or incurred by reason of: (a) any damage to any property (including the property of
    Landlord), or any injury (including death) to any person, occurring in, on, or about any portion of the Premises, except to the extent caused by or arising from the gross negligence or willful misconduct of Landlord or the Landlord Parties; (b) any
    Alterations, work, or other thing done by Tenant or any Tenant Parties in or about any portion of the Premises, or from transactions of Tenant concerning any portion of the Premises; (c) Tenant&#8217;s failure to comply with any Applicable Laws; (d) any
    breach or default by Tenant of any representation, covenant or other term of this Lease; provided that Tenant shall not be obligated to so indemnify Landlord to the extent any such matter arises from, or is caused by, the willful misconduct or gross
    negligence of Landlord or the Landlord Parties; or (e) Tenant&#8217;s use and occupancy of the Premises. Tenant&#8217;s agreement to indemnify, defend and hold the Landlord and the Landlord Parties (the &#8220;<b>Indemnitees</b>&#8221;) harmless is conditioned upon the
    Indemnitees (i) providing written notice to Tenant of any claim, demand or action arising out of the indemnified activities within thirty (30) days after Landlord has actual knowledge of such claim, demand or action, provided that the failure to so
    notify Tenant will not relieve Tenant of its obligations hereunder except to the extent such failure has actually materially prejudiced Tenant; (ii) permitting Tenant to assume full responsibility to investigate, prepare for and defend against any such
    claim or demand, subject to Landlord&#8217;s reasonable approval of any counsel used in the defense of such claim or demand; (iii) assisting Tenant, at Tenant&#8217;s expense, in the reasonable investigation of, preparation of and defense of any such claim or
    demand; and (iv) not settling such claim or demand that would result in a payment in excess of $100,000 (individually or in the aggregate) without Tenants&#8217; prior written consent, which shall not be unreasonably withheld, conditioned, or delayed. &#8220;<b>Claims</b>&#8221;
    mean claims, demands, losses, penalties, fines, liabilities, actions (including informal proceedings), settlements, judgments, damages, reasonable costs, and reasonable expenses (including reasonable attorneys&#8217; fees and consultants&#8217; fees, court costs,
    and other litigation expenses) of whatever kind or nature, known or unknown, contingent or otherwise, incurred or suffered by, or asserted against, the party in question.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant hereby releases Landlord and the Landlord
    Parties from any and all liability for any loss or claim, including all economic losses and all consequential and indirect losses, as a result of loss, damage or injury to the property and persons of Tenant and its employees, as a result of any
    occurrence in, upon or at the Premises or the occupancy or use by the Tenant of the Premises, including damage to the Building or loss of access to the Premises, whether or not such loss or claim may have arisen out of the acts, omissions or negligence
    of Landlord, the Landlord Parties or those for whom Landlord or the Landlord Parties are in law responsible. Except with respect to Sections 1.3 and 3.3.4, Landlord hereby releases Tenant from any and all liability for consequential or special damages,
    including lost profits (which shall not limit the rights and remedies of Landlord expressly provided in this Lease).</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">29</font></div>
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  </div>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">6.2</td>
        <td style="text-align: justify"><u>Insurance</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Insurance</u>. Landlord shall
    obtain and keep in force throughout the Term the following coverages in the following amounts: (a) commercial general liability insurance on an &#8220;occurrence&#8221; basis on the current ISO CG 00 01 occurrence form or its equivalent with a deductible
    reasonably acceptable to Landlord with a limit of not less than $5,000,000 per occurrence, (b) property damage insurance covering the core and shell of the Buildings and structural elements of other improvements situated upon the Premises on a
    replacement cost basis against loss or damage as provided by the standard fire and extended coverage policy, including, without limitation, earthquake and terrorism, and all other risks of direct physical loss as insured against under a special
    extended coverage endorsement in amounts and with a deductible determined by Landlord in its commercially reasonable discretion, (c) boiler and machinery insurance on a repair or replace basis, (d) business interruption insurance with respect to
    insurance required under (b) and (c) above with an indemnity period determined by Landlord, and (e) any such other insurance as Landlord&#8217;s lender may require. Tenant shall provide Landlord with such information from time to time as Landlord may
    reasonably require in connection with Landlord&#8217;s determination of the insurance required pursuant to clause (b), above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Insurance.</u> Tenant shall procure
    and maintain during the Lease Term, at its sole cost and expense, a policy or policies of insurance protecting Landlord and Tenant against each of the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Commercial general
    liability insurance with respect to the operations of Tenant insuring against bodily injury or death and property damage in amounts (i) not less than $10,000,000 in the aggregate,(ii) not less than $2,000,000 per occurrence and (iii) not less than
    $10,000,000 of excess umbrella liability insurance. Such insurance shall contain separation of insured clauses and separation of insureds, with Landlord and any third party now or hereafter providing financing to Landlord where such third party has a
    security interest in the Premises under such financing shall be included as additional insureds. Tenant may satisfy the foregoing limits through any combination of primary and umbrella/excess policies, provided the combined total coverage is not less
    than $20,000,000 in the aggregate. The amount of such commercial general liability insurance shall be increased from time to time as Landlord may reasonably determine. All such bodily injury and property damage insurance shall insure Tenant&#8217;s exposure
    with respect to the indemnity agreement as to personal injury or property damage contained in Section 6.1 herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Insurance covering Tenant&#8217;s
    construction, alterations, additions or improvements permitted herein (other than the core and shell of the Buildings and structural elements of other improvements), existing tenant improvements, trade fixtures and personal property, in an amount not
    less than 100% of their full replacement cost from time to time during the Lease Term, providing protection on an all risk basis, including, without limitation, coverage for earthquakes, for the repair or replacement of the property damaged or
    destroyed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Pollution Legal Liability
    that provides first party coverage for clean-up costs and third party coverage for bodily injury and property damage resulting from pre-existing and future contamination conditions, of at least Five Million Dollars ($5,000,000.00) per pollution event;
    such coverage shall specifically include this lease as an insured contract.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">30</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The minimum limits of
    insurance required to be carried by Tenant shall not limit Tenant&#8217;s liability. All policies of insurance to be provided by Tenant shall be issued by insurance companies, with general policy holder's rating of not less than A and a financial rating of
    not less than Class VIII as rated in the most current available "Best's" Insurance Reports, and admitted to do business in the State of California. Such policies shall be issued in the name of Tenant, with Landlord, Landlord&#8217;s managing agent, lenders,
    and any other party designated by Landlord (&#8220;<b>Additional Insured Parties</b>&#8221;) included as an additional insured. Tenant&#8217;s property insurance and any builder&#8217;s risk policy carried by Tenant or its contractors shall identify Landlord or, at Landlord&#8217;s
    direction, Landlord&#8217;s lender, as a loss payee. The full replacement cost of improvements under Tenant&#8217;s property insurance may be designated by Landlord in the good faith exercise of Landlord's judgment. In the event that Tenant does not agree with
    Landlord's designation, Tenant shall have the right to submit the matter to an insurance appraiser reasonably selected by Landlord and paid for by Tenant. The insurance appraiser shall submit a written report of his appraisal, and if said report
    discloses that the improvements are not insured as therein required, Tenant shall promptly obtain the insurance required. The policies provided by Tenant shall be for the mutual and joint benefit and protection of Landlord and Tenant, and certificates
    of insurance shall be delivered to the Landlord within ten (10) days after the Lease Commencement Date and, thereafter, within thirty (30) days after to the expiration of the term of each such policy. Upon Landlord&#8217;s request, Tenant shall deliver to
    Landlord, in lieu of such certificates, copies of the policies of insurance required to be carried under Section 6.2.2 showing that the Additional Insured Parties are named as additional insureds (with respect to the applicable policies). Upon the
    expiration or termination of any such policy, renewal or additional policies shall be procured and maintained by the Tenant to provide the required coverage. All policies of insurance delivered to Landlord must contain a provision that the company
    writing said policy will provide Landlord with thirty (30) days&#8217; notice in writing in advance of any cancellation or lapse or the effective date of any reduction in the amounts of insurance (except in the event of non-payment of premium, in which case
    ten (10) days&#8217; written notice shall be given). Notwithstanding the foregoing, if the foregoing requirement that the insurance company provide prior notice to Landlord of cancellation or material change of the applicable policy cannot reasonably be
    obtained based on then-prevailing insurance industry practices, Tenant shall so advise Landlord of such unavailability and shall instead shall use reasonable efforts to cause its insurer to provide Landlord, and in any event Tenant shall provide
    Landlord with, notice of any such cancellation of any of Tenant&#8217;s insurance policies. All of Tenant&#8217;s commercial general liability, property damage and other casualty policies shall be written as primary policies, not contributing with and not in
    excess of coverage which Landlord may carry. Tenant agrees that if, after the Commencement Date, Tenant does not take out and maintain the insurance required under this Section 6.2, Landlord may (but shall not be required to) procure, and thereafter
    maintain, said insurance on Tenant's behalf, and any costs or expenses incurred by Landlord in connection therewith, plus an administration fee of ten percent (10%) of the cost, shall promptly be paid by Tenant to Landlord as Additional Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Notwithstanding anything to
    the contrary, Tenant's obligation to carry the insurance described in this Section 6.2.2 may be brought within the coverage of a so-called blanket policy or policies of insurance carried and maintained by the Tenant, provided that (i) Landlord will be
    an additional insured thereunder as its interests may appear; (ii) the coverage afforded Landlord will not be reduced or diminished by reason of the use of such blanket policy of insurance; and (iii) the requirements set forth herein are otherwise
    satisfied. In the event of any Claims covered by Tenant&#8217;s insurance, Tenant shall, within 10 days following Landlord&#8217;s written request, provide Tenant with copies of the applicable insurance policies carried by Tenant pursuant to this Lease.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">31</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.2.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Release of Subrogation Rights</u>. Tenant and
    Landlord each hereby releases the other from liability and waives all right to recover against the other for any loss from perils insured against under their property insurance policies, including any extended coverage and special form endorsements to
    said policies; provided, however, this <u>Section 6.2.3</u> shall be inapplicable if it would have the effect, but only to the extent that it would have the effect of invalidating any insurance coverage of Landlord or Tenant. Tenant and Landlord&#8217;s
    property damage policies shall contain, if available, a waiver of subrogation clause.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">6.2.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Insurance for Alterations</u>. During the
    performance of any Alterations by Tenant, (a) the insurance required under this <u>Section 6.2</u> shall extend to all of Tenant&#8217;s consultants and contractors (and subcontractors of any tier) and shall include injuries to persons and damage to
    property arising in connection with such Alterations and (b) Tenant shall also maintain such other insurance as Landlord may reasonably require, including all-risk builder&#8217;s insurance, each of which policies shall name Landlord and Landlord&#8217;s lender as
    additional insureds and loss payees. Tenant shall give to Landlord copies of the policies of such insurance prior to commencing construction of such Alterations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: -0.2pt">ARTICLE 7<br>
    THIRD PARTIES</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: -0.2pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Subordination, Attornment and
      Non-Disturbance</u>. This Lease shall be automatically subject and subordinate at all times to the lien of any first priority mortgages or deeds of trust on, against, or affecting any portion of the Premises, or Landlord&#8217;s interest or estate in any
    portion of the Premises, and to all renewals, modifications, consolidations, replacements, and extensions thereof (each, a &#8220;<b>Mortgage</b>&#8221;); provided that, as a condition precedent to such subordination, Tenant must receive a fully executed
    subordination, non-disturbance and attornment agreement substantially in the form attached as Exhibit E hereto, or in such other commercially reasonable form as required by Landlord&#8217;s Mortgagee (as hereinafter defined) (a &#8220;<b>SNDA</b>&#8221;) from any
    current and future encumbrance holder (each, a &#8220;<b>Mortgagee</b>&#8221;) with such changes as reasonably requested by Tenant. Landlord shall request a SNDA from each present and any future Mortgagee seeking to subordinate this Lease to the lien of its
    Mortgage and deliver the same to Tenant. In the event Mortgagee enforces it rights under the Mortgage, Tenant, at Mortgagee&#8217;s option, will attorn to Mortgagee or its successor; provided, however, that, subject to the terms of any SNDA between Tenant
    and such Mortgagee (which shall govern in the event of any conflicts with the provisions of this Section 7.1), Mortgagee or its successor shall not be liable for or bound by (i) any payment of any Rent installment that may have been made more than
    thirty (30) days before the due date of such installment, (ii) any act or omission of or default by Landlord under this Lease (but Mortgagee, or such successor, shall be subject to the continuing obligations of landlord under the Lease arising from and
    after such succession, but only to the extent of Mortgagee&#8217;s, or such successor&#8217;s, interest in the Premises as provided in Article 12), (iii) any then-exercisable credits, claims, setoffs or defenses that Tenant may have against Landlord, or (iv) any
    obligation to provide tenant improvements allowances or perform tenant improvements to be provided by Landlord hereunder.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">32</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Mortgagee&#8217;s Right to Cure</u>.
    Notwithstanding anything to the contrary in this Lease, before exercising any right (a) of offset, counterclaim, reduction, deduction, or abatement against Tenant&#8217;s payment of Rent under this Lease or (b) to terminate the Lease or to claim a partial or
    total eviction, in each case arising from Landlord&#8217;s default under this Lease, (i) Tenant shall provide to each Mortgagee whose name and address has been furnished in writing to Tenant with written notice of the default by Landlord giving rise to same,
    and (ii) Mortgagee shall have a period of thirty (30) days after the last date on which Landlord could have cured such default within which such Mortgagee will be permitted, but not be obligated, to cure such default. If such default cannot be cured
    within such thirty-(30)-day period, then such Mortgagee shall have such additional time as may be necessary to cure such default, if prior to the end of such thirty-(30)-day period such Mortgagee has commenced and is diligently pursuing such cure or
    the remedies under the Mortgage necessary for Mortgagee to be able to effect such cure, in which event Tenant shall have no right with respect to such default while such cure and remedies are being diligently pursued by such Mortgagee. Notwithstanding
    the foregoing, such Mortgagee shall have no obligation to cure (and shall have no liability or obligation for not curing) any default by Landlord. In addition, as to any default by Landlord the cure of which requires possession and control of the
    Premises, provided that such Mortgagee undertakes by written notice to Tenant to exercise reasonable efforts to cure or cause to be cured by a receiver such default within the period permitted by this <u>Section 7.2</u>, such Mortgagee&#8217;s cure period
    shall continue for such additional time as such Mortgagee may reasonably require to either: (A) obtain possession and control of the Premises with due diligence and thereafter cure the default with reasonable diligence and continuity; or (B) obtain the
    appointment of a receiver and give such receiver a reasonable period of time in which to cure the default.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Sale of the Premises</u>. Subject to the
    provisions of Article 11, if Landlord sells or conveys the Premises, such sale or conveyance shall release Landlord from any liability from and after such sale or conveyance upon any of the covenants or conditions, expressed or implied, contained in
    this Lease in favor of Tenant (to the extent such liability is expressly assumed by such transferee), and in such event, Tenant agrees to look solely to the successor-in-interest of Landlord in and to this Lease with respect to such liabilities that
    are incurred from and after such sale or conveyance. In the event Landlord enters into a purchase and sale agreement for the sale or conveyance of the Premises, in the event such purchaser is an entity engaged primarily in the business of research,
    development, manufacturing, sale, or marketing of a biopharmaceutical product (a &#8220;<b>Pharma Competitor</b>&#8221;), then the Pharma Competitor shall execute a non-disclosure and confidentiality agreement substantially in the form attached hereto as <u>Exhibit








      F</u>; provided, however, that Tenant shall negotiate in good faith in the event the Pharma Competitor wishes to deviate from the form attached as <u>Exhibit F</u>. Except as set forth in this <u>Section 7.3</u>, this Lease shall not be affected by
    any such sale or conveyance and Tenant agrees to attorn to the purchaser or assignee. Landlord shall transfer or deliver the Security Deposit to Landlord&#8217;s successor-in-interest and thereupon Landlord shall be discharged from any further liability with
    regard thereto.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Estoppel Certificates</u>. Within ten (10)
    business days after Landlord&#8217;s written request, Tenant shall execute and deliver to Landlord and any of Landlord&#8217;s then existing or prospective lenders, investors, or purchasers of any portion of the Premises, a certificate substantially in the form
    attached as <u>Exhibit C</u>, or in such other commercially reasonable form and containing such other information as Landlord or any such lenders, investors, or purchasers, may reasonably require. Any certificate delivered in accordance with this <u>Section








      7.4</u> may be relied upon by any such lender, investor, or purchaser. Within ten (10) business days after Tenant&#8217;s request, Landlord shall execute and deliver to Tenant and any of Tenant&#8217;s then existing or prospective lenders, investors, or
    purchasers, a statement in writing certifying that Tenant is in possession of the Premises under the terms of this Lease, that this Lease is unmodified and in full force and effect (or, if there have been modifications, that this Lease is in full force
    and effect, as modified, and setting forth such modifications), stating the dates to which rent has been paid, and either stating that no defaults exist hereunder, or specifying each such default of which Landlord may have knowledge, and such other
    matters as may be reasonably requested by Tenant.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">33</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt">7.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Liens</u>.
      Tenant shall, within fifteen (15) business days of written notice of filing, discharge (either by payment or by filing of the necessary bond, insure over, or otherwise) any mechanic&#8217;s, materialman&#8217;s or other lien or encumbrance against any portion of
      the Premises that arises out of any payment due for, or purported to be due for, any labor, services, materials, supplies or equipment alleged to have been furnished to or for Tenant. If Tenant shall fail to so discharge such lien or encumbrance
      (either by payment or by filing of the necessary bond, insure over or otherwise) then, such failure shall be an Event of Default under this Lease and, in addition to any other right or remedy of Landlord, Landlord may discharge the same (either by
      payment or by filing of the necessary bond or otherwise), and any payment, costs and expenses incurred by Landlord in connection therewith, including reasonable attorneys&#8217; fees, shall be repaid together with interest thereon at the rate set forth in
      <u>Section 2.3</u> from the date of payment. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant may contest any lien (and Landlord shall not discharge such lien at Tenant&#8217;s expense for so long as Tenant is diligently
      pursuing such contest) if (i) such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord in writing of such dispute, (iii) Tenant has or establishes unrestricted cash
      reserves to in an amount equal to 125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contested lien and (iv) such lien is fully bonded by Tenant to the reasonable
      satisfaction of Landlord and any Mortgagee.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 8</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>EVENTS OF DEFAULT &amp; REMEDIES</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">8.1</td>
        <td style="text-align: justify"><u>Events of Default</u>. &#8220;<b>Event of Default</b>&#8221; means any of the following:</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant fails to pay when
    due any Rent, and such failure continues for five (5) business days after Landlord delivers to Tenant notice thereof; provided, however, Landlord shall not be required to provide prior notice of Tenant&#8217;s failure to pay any recurring obligation to pay
    any Base Rent or any monthly payment of estimated Taxes or Insurance Expenses more than twice during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be an Event of Default if Tenant fails to pay the amount when due
    and such failure continues for five (5) business days after the due date;</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">34</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>except as otherwise
    provided in this Lease, Tenant fails to comply with any term, provision, or covenant of this Lease and such failure continues for thirty (30) days after Landlord gives to Tenant Notice thereof (but if such failure is curable but cannot reasonably be
    cured during such 30-day period, and if Tenant has commenced such cure promptly and in any case within such 30-day period and thereafter has diligently pursued such cure to completion, then such 30-day period shall be extended to ninety (90) days);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant fails to obtain and
    keep in force at all times any insurance required under this Lease, and such failure continues for five (5) days after Landlord gives to Tenant Notice thereof;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant fails to deliver to
    Landlord, within fifteen (15) business days after Landlord gives Tenant Notice thereof, any instrument or assurance required under this Lease;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The filing by Tenant in any
    court pursuant to any statute or petition in bankruptcy or insolvency or for reorganization or arrangement for the appointment of a receiver or all of a portion of Tenant&#8217;s property the filing against Tenant of any such petition, or the commencement of
    a proceeding for the appointment of a trustee, receiver or liquidator for Tenant, or of any property of Tenant, or a proceeding by any governmental authority for the dissolution or liquidation of Tenant, if such proceeding shall not be dismissed or
    trusteeship discontinued within sixty (60) days of commencement of such proceeding or the appointment of such trustee or receiver; or the making by Tenant of an assignment for the benefit of creditors. Tenant hereby stipulates to the lifting of the
    automatic stay in effect and relief from such stay for Landlord in the event Tenant files a petition under the United States Bankruptcy Laws, for the purpose of landlord pursuing its rights and remedies against Tenant;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s failure to cause
    to be released any mechanics liens filed against the Premises within twenty (20) days after the date Tenant is notified that the same shall have been filed or recorded, subject to Tenant&#8217;s right to dispute liens as set forth in <u>Section 7.5</u>;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Abandonment of the Premises
    pursuant to California Civil Code Section 1951.3, or failure by Tenant or a transferee permitted pursuant to Article 5 to occupy at least sixty percent (60%) of the Premises for a period of ninety (90) consecutive days or more for any reason other than
    restoration following a casualty or condemnation, Force Majeure affecting Tenant&#8217;s ability to operate within the Premises, and temporary cessations in order to complete Alterations in accordance with this Lease, provided that it shall not be deemed to
    be a failure to occupy for purposes of this clause (ii) if the applicable portion of the Premises remains fully furnished with the necessary equipment to conduct business operations consistent with the Permitted Use as it was undertaken prior to such
    failure to occupy, with regular repair, maintenance, and cleaning occurring in accordance with the terms of this Lease, no other Event of Default has occurred, and Tenant is actively marketing the applicable portion of the Premises for sublease (or
    marketing this Lease for assignment);</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">35</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(h)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s failure to provide
    a SNDA within the period required by Section 7.1 or Tenant&#8217;s failure to provide a certificate within the time period required by Section 7.4 and such failure continues for five (5) business days after Landlord delivers to Tenant notice thereof;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;Tenant performs a Transfer in violation of Article 5, or</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(j)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>If Landlord elects, in its
    sole discretion, the occurrence of any &#8220;Event of Default&#8221; under the Companion Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">8.2</td>
        <td style="text-align: justify"><u>Remedies</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Upon Event of Default</u>. Upon the
    occurrence of any Event of Default, Landlord shall have the option to pursue any one or more of the following remedies without any Notice or demand whatsoever (except as expressly provided herein), concurrently or consecutively and not alternatively
    (in addition to any other remedies available to Landlord at law or in equity), all of which remedies shall be distinct, separate and cumulative:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>.
    Landlord may terminate this Lease upon notice to Tenant, in which event Tenant shall vacate the Premises immediately and deliver possession of the Premises to Landlord in the condition which Tenant is required to surrender the Premises at the
    expiration of the Term (Tenant hereby waives, relinquishes and releases for itself and for all those claiming under Tenant any right of occupancy of the Premises following termination of this Lease, and any right to redeem or reinstate this Lease by
    order or judgment of any court or by any legal process or writ under Applicable Laws, including, without limitation, California Code of Civil Procedure Sections 473 and 1179, and California Civil Code Section 3275), and if Tenant fails to do so, then
    Landlord may, after due process of law, enter upon and take possession of the Premises, and expel or remove Tenant and any other person who may be occupying the Premises or any portion thereof, without being liable for prosecution or any claim or
    damages therefor. Upon termination of the Lease as provided in this Section, Landlord may recover from Tenant the following: (i) the worth at the time of award of any unpaid rent which has been earned at the time of such termination; plus (ii) the
    worth at the time of award of the amount by which the unpaid rent which would have been earned after termination until the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iii) the worth
    at the time of award of the amount by which the unpaid rent for the balance of the Term after the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iv) any other amount necessary to
    compensate Landlord for all the detriment proximately caused by Tenant&#8217;s failure to perform its obligations under this Lease or which in the ordinary course of things would be likely to result therefrom, specifically including but not limited to,
    attorneys&#8217; fees, brokerage commissions and advertising expenses incurred, expenses of remodeling the Premises or any portion thereof for a new tenant, whether for the same or a different use, and any special concessions made to obtain a new tenant;
    plus (v) at Landlord&#8217;s election, such other amounts in addition to or in lieu of the foregoing as may be permitted from time to time by Applicable Law. The term &#8220;rent&#8221; as used in this Section 8.2.1(a) shall be deemed to be and to mean all sums of every
    nature required to be paid by Tenant pursuant to the terms of this Lease, whether to Landlord or to others, including, without limitation, late charges and interest. As used in Sections 8.2.1(a)(i) and (ii), the &#8220;worth at the time of award&#8221; shall be
    computed by allowing interest at the rate set forth in Section 2.4 above, but in no case greater than the maximum amount of such interest permitted by Applicable Law. As used in Section 8.2.1(a)(iii), the &#8220;worth at the time of award&#8221; shall be computed
    by discounting such amount at the discount rate of the Federal Reserve Bank of San Francisco at the time of award plus one percent (1%). Landlord shall have no obligation to relet the Premises or any part thereof and shall in no event be liable for
    failure to relet the Premises or any part thereof, or, in the event of any such reletting, for refusal or failure to collect any rent due upon such reletting. No such refusal or failure shall operate to relieve Tenant of any liability under this Lease.
    Tenant shall instead remain liable for all unpaid Rent and for all such expenses. This paragraph is expressly intended to afford Landlord the remedies provided for in California Civil Code &#167; 1951.2.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">36</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Possession</u>. Landlord
    may re-enter the Premises without terminating this Lease by Notice to Tenant and sublet the whole or any part thereof for the account of Tenant upon as favorable terms and conditions as the market will allow; <u>provided</u>, <u>however</u>, that
    Tenant shall have not less than thirty (30) days following such re-entry to remove Tenant&#8217;s Personalty from the Premises. In the latter event (a) Landlord shall have the right to collect any Rent which may thereafter become due and payable under such
    sublease and to apply the same first, to the payment of any expenses incurred by Landlord in dispossessing Tenant and in subletting the Premises, and second, to the payment of the Rent herein reserved and to the fulfillment of Tenant&#8217;s other covenants
    hereunder, and (b) Tenant shall be liable for amounts equal to the Rent as the same would under the terms of this Lease become due, less any amounts actually received by Landlord and applied on account of Rent as aforesaid. Landlord shall have the
    remedy described in California Civil Code Section 1951.4 (lessor may continue lease in effect after lessee&#8217;s breach and abandonment and recover rent as it becomes due, if lessee has the right to sublet or assign, subject only to reasonable
    limitations). Accordingly, if Landlord does not elect to terminate this Lease due to any Event of Default, Landlord may, from time to time, without terminating this Lease, enforce all of its rights and remedies under this Lease, including, without
    limitation, the right to recover all Rent as it becomes due.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Subleases of Tenant</u>.
    Whether or not Landlord elects to terminate this Lease, Landlord may terminate any and all subleases or other consensual arrangements for possession or occupancy of the Premises entered into by Tenant or any subtenant of Tenant, or may succeed to
    Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in such subleases or other arrangements. If Landlord elects to succeed to Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in any such subleases or other arrangements, then as of the date of Notice by Landlord of such
    election (i) Tenant shall have no further right to, or interest in, the rent or other consideration receivable thereunder, and (ii) any sublessee or other occupant of the Premises shall attorn to and recognize Landlord as its landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Right to Perform
      Tenant&#8217;s Covenants</u>. If Tenant shall at any time fail to pay any Taxes or to take out, pay for, maintain or deliver any of the insurance provided for in this Lease, or shall fail to make any other payment or perform any obligation under this
    Lease, and such failure continues beyond applicable notice and cure periods (or without any notice and right to cure where required to protect life or property), then Landlord may, without waiving or releasing Tenant from any obligations of Tenant in
    this Lease contained, pay any such Tax, effect any such insurance coverage and pay premiums therefor, and make any other payment or perform any other act which Tenant is obligated to perform under this Lease, in such manner and to such extent as
    Landlord shall, in its sole discretion, deem necessary. In exercising any such rights, Landlord may pay necessary and incidental costs and expenses including reasonable attorneys&#8217; fees. All sums so paid by Landlord and all necessary and incidental
    costs and expenses in connection with the performance of any such act by Landlord, together with interest thereon at the Interest Rate, shall be payable to Landlord on demand. If Landlord incurs any third-party expenses to cure a breach of any
    non-monetary obligation of Tenant, Tenant shall also pay an administrative charge equal to ten percent (10%) of the cost of the work performed by Landlord. Landlord shall have no obligation to perform on Tenant&#8217;s behalf and if Landlord does so,
    Landlord shall not be liable to Tenant for any damage resulting from its actions.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Other Remedies</u>. In
    addition to the remedies set forth in this Lease, Landlord shall have all other remedies provided by law or statute to the same extent as if fully set forth herein word for word (including, without limitation, the right to enforce Tenant&#8217;s specific
    performance of each and every covenant, condition and other provisions of this Lease). No remedy herein conferred upon, or reserved to Landlord shall exclude any other remedy herein or by law provided, but each shall be cumulative.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Form of Payment Following Event of Default</u>.
    Following the occurrence of a monetary Event of Default, Landlord shall have the right to require that any or all subsequent amounts paid by Tenant to Landlord under this Lease, whether relating to the Event of Default in question or otherwise, be paid
    in the form of wire transfer or immediately available funds, or by other means approved by Landlord, notwithstanding any prior acceptance by Landlord of payments from Tenant in any different form.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Mitigation of Damages</u>. Except as required
    by law, Landlord shall have no obligation to mitigate its damages. If Landlord is required by law to mitigate its damages under this Lease, then (a) Landlord shall be required only to use reasonable efforts to so mitigate, which shall not exceed such
    efforts as commercial landlords generally use to lease similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California; (b) Landlord shall not be deemed to have failed to so mitigate if Landlord leases
    less than all of the Premises; and (c) Landlord&#8217;s failure to so mitigate shall only reduce the Rent to which Landlord is entitled. Tenant acknowledges that Landlord&#8217;s rejection of a prospective replacement tenant based on an offer of rentals below
    published rates for new leases of similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California at the time in question, or containing terms less favorable than those contained herein, shall not give
    rise to a claim by Tenant that Landlord failed to so mitigate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Waiver of Right of Redemption</u>. Tenant
    (for itself and all others claiming through Tenant) irrevocably waives and releases any rights under any law now or hereafter existing to redeem or reinstate this Lease or Tenant&#8217;s right of occupancy of the Premises after termination of this Lease,
    including, without limitation, any and all rights conferred by Section 3275 of the Civil Code of California and by Sections 1174(c) and 1179 of the Code of Civil Procedure of California..</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">38</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Reimbursement of Expenses</u>. In the case of
    termination of this Lease pursuant to this Section 8.2, Tenant shall reimburse Landlord for all expenses arising out of such termination, including without limitation, all costs incurred in collecting amounts due from Tenant under this Lease (including
    legal fees, costs of litigation and the like); all expenses incurred by Landlord in attempting to relet the Premises or parts thereof (including advertisements, brokerage commissions, Tenant&#8217;s allowances, costs of preparing space, and the like); all of
    Landlord&#8217;s then unamortized costs of any work allowances provided to Tenant for the Premises; and all Landlord&#8217;s other reasonable expenditures necessitated by the termination. The reimbursement from Tenant shall be due and payable immediately from time
    to time upon notice from Landlord that an expense has been incurred, without regard to whether the expense was incurred before or after the termination.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">8.2.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Claims in Bankruptcy</u>. Nothing herein
    shall limit or prejudice the right of Landlord to prove and obtain in a proceeding for bankruptcy, insolvency, arrangement or reorganization, by reason of the termination, an amount equal to the maximum allowed by a statute or Applicable Law in effect
    at the time when, and governing the proceedings in which, the damages are to be proved, whether or not the amount is greater to, equal to, or less than the amount of the loss or damage that Landlord has suffered.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">8.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord Default</u>. If Landlord shall
    fail to perform any material obligation under this Lease required to be performed by Landlord, Landlord shall not be deemed to be in default hereunder nor subject to claims for damages of any kind, unless such failure shall have continued for a period
    of thirty (30) days after written notice thereof by Tenant or, if such failure is curable but cannot reasonably be cured during such 30-day period, such additional time as it would reasonably take to cure. If Landlord shall fail to cure within the time
    permitted for cure herein, Landlord shall be liable to Tenant for those actual damages sustained by Tenant as a result of Landlord&#8217;s default and Tenant shall also have the right to pursue injunctive relief against Landlord, to the extent available
    under Applicable Laws. Except as may be expressly provided in this Lease, in no event shall Tenant have the right to terminate the Lease nor shall Tenant&#8217;s obligation to pay Base Rent or other charges under this Lease abate based upon any default by
    Landlord of its obligations under the Lease. In no event shall Landlord or any Landlord Related Party ever be liable to Tenant for loss of profits, loss of business, or indirect or consequential damages suffered by Tenant from whatever cause.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">8.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Non-Waiver</u>. The failure of Landlord to
    insist upon strict performance of any of the terms, covenants, conditions or agreements contained herein shall not be deemed a waiver of any rights or remedies that Landlord may have, and shall not be deemed a waiver of any subsequent breach or default
    in the performance of any of the terms, covenants, conditions or agreements contained herein. The performance of each and every term, covenant, condition and agreement to be performed by Landlord pursuant to this Lease shall not be a condition
    precedent to Landlord&#8217;s right to collect Rent or to enforce this Lease. Further, pursuant to the requirements of California Code of Civil Procedure Section 1161.1(c), Tenant is hereby placed on actual notice that Landlord&#8217;s acceptance of Rent shall not
    constitute a waiver by Landlord of (a) any preceding breach by Tenant of any provision of this Lease, other than the failure of Tenant to pay the particular Rent so accepted; or (b) any of Landlord&#8217;s rights, including, without limitation, any rights
    Landlord may have to recover possession of the Premises or to sue for any remaining Rent owed by Tenant.</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 9</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">CASUALTY &amp; CONDEMNATION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 60.45pt">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">9.1</td>
        <td style="text-align: justify"><u>Casualty</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Generally</u>. Subject to <u>Section 9.1.2</u>
    below, if the Premises are damaged by fire, the elements or other casualty (collectively a &#8220;<b>Casualty</b>&#8221;), Tenant shall promptly notify Landlord of the same. Except as expressly set forth below, this Lease shall not terminate in the event of damage
    to the Premises by other casualty, nor any other obligation of Tenant hereunder be abated or affected in any way. If all or any portion of the Premises becomes untenantable or inaccessible by a Casualty, Landlord shall cause a general contractor
    selected by Landlord to provide Landlord and Tenant with a written estimate of the amount of time required, using standard working methods, to substantially complete the repair and restoration of the affected portion of the Premises (&#8220;<b>Completion
      Estimate</b>&#8221;). Landlord shall promptly forward a copy of the Completion Estimate to Tenant. Notwithstanding anything to the contrary contained in this Lease, Landlord and Tenant hereby waive the provisions of any Law relating to the matters
    addressed in this Section, and agree that their respective rights for damage to or destruction of the Premises shall be those specifically provided in this Lease, which shall constitute an express agreement between the parties with respect thereto, and
    Landlord and Tenant hereby agree that any Applicable Law, including Sections 1932(2) and 1933(4) of the California Civil Code, with respect to any rights or obligations concerning damage or destruction of leased or hired property, shall have no
    application to this Lease or to any damage or destruction to all or any part of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>. Notwithstanding <u>Section
      9.1.1</u>, if the Completion Estimate indicates that the Premises cannot be made tenantable within twenty-four (24) months from the date the repair is started, then either party shall have the right to terminate this Lease upon written notice to the
    other within ten (10) days after Tenant&#8217;s receipt of the Completion Estimate, which notice, if sent by Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. Tenant, however, shall not have the
    right to terminate this Lease if the Casualty was caused by the negligence or intentional misconduct of Tenant or any Tenant Parties. If (i) the Completion Estimate indicates that the Premises can be made tenantable within thirty-six (36) months from
    the date the repair is started, and (ii) Tenant terminates this Lease pursuant to the first sentence of this <u>Section 9.1.2</u>., then, within thirty (30) days after receipt of Tenant&#8217;s termination notice, Landlord may, in its sole and absolute
    discretion, negate Tenant&#8217;s termination by providing notice to Tenant that Landlord agrees to an abatement of Base Rent beginning immediately following the twenty-fourth (24<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>)
    month after the date the repair is started and ending on the date when Landlord has substantially completed the repair and restoration of the affected portion of the Premises. In addition, if the Premises are damaged by fire, the elements or other
    casualty during the last twelve (12) months of the Term, and the Completion Estimate shows that the restoration cannot be completed within one hundred twenty (120) days after the Casualty, then either party shall have the right, in lieu of Tenant
    fulfilling its obligations under <u>Section 9.1.1</u> above, to terminate this Lease as of the date of the Casualty by notice to the other party within ten (10) business days after the delivery of the Completion Estimate, which notice, if sent by
    Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. If Tenant elects to terminate the Lease pursuant to this <u>Section 9.1.2</u>, Tenant shall (1) assign to Landlord all of Tenant&#8217;s right,
    title and interest in and to any property insurance proceeds received in connection with such casualty for the Tenant Improvements (defined below) and (2) pay to Landlord an amount equal to Tenant&#8217;s deductible under any insurance and/or any applicable
    self-insured retention amount covering the Tenant Improvements. In addition, Landlord, by notice to Tenant within ninety (90) days after the date of the Casualty, shall have the right to terminate this Lease if (1) any Mortgagee requires that the
    insurance proceeds be applied to the payment of the mortgage debt; or (2) a material uninsured loss to the Buildings or Premises occurs, and, in either case, Tenant does not provide Landlord with sufficient funds (or evidence of the same satisfactory
    to Landlord) to complete such restoration within thirty (30) days after Landlord&#8217;s termination notice.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Restoration</u>. If this Lease is not
    terminated, Landlord shall promptly and diligently, subject to reasonable delays for insurance adjustment or other matters beyond Landlord&#8217;s reasonable control, restore the core and shell of the Buildings and structural elements of other improvements
    situated upon the Premises, subject to the following provisions. Such restoration shall be to substantially the same condition that existed prior to the Casualty, except for modifications required by Applicable Law or any other modifications deemed
    desirable by Landlord (&#8220;<b>Landlord&#8217;s Restoration</b>&#8221;). Landlord shall be paid a construction management fee equal to three percent (3%) of the hard and soft costs of construction in connection with Landlord&#8217;s Restoration. In no event shall Landlord
    be required to spend more for the Landlord&#8217;s Restoration than the proceeds received by Landlord, whether from Landlord&#8217;s insurance proceeds or proceeds from Tenant. Landlord shall not be liable for any inconvenience to Tenant, or injury to Tenant&#8217;s
    business resulting in any way from the Casualty or the repair thereof. Landlord shall not be responsible for restoration of any portion of the non-structural tenant improvements, any improvements or fixtures installed for Tenant&#8217;s specific business
    operations, or any Alterations, including, without limitation, the Conference Center Alterations (collectively, the &#8220;<b>Tenant Improvements</b>&#8221;). If this Lease is not terminated, upon the substantial completion of Landlord&#8217;s Restoration, Tenant shall
    diligently and promptly repair all such damage and restore the Tenant&#8217;s Improvements (the &#8220;<b>Tenant&#8217;s Restoration</b>&#8221;) to substantially the same quality, use and usability to the Buildings and related improvements that existed immediately prior to
    the Casualty.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.1.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No abatement of Rent</u>. If the Premises are
    damaged or destroyed by casualty, then the Rent shall not be abated and Tenant shall not be entitled to any compensation or damages from Landlord for loss of the use of the Premises, damage to Tenant&#8217;s Personalty or to any Alterations, or any
    inconvenience occasioned by any damage, repair, or restoration.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.1.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Insurance Proceeds</u>. Tenant shall be
    entitled to any and all of the insurance proceeds payable for the damage to the Tenant Improvements, <u>provided</u>, <u>however</u>, that if Tenant elects to terminate this Lease pursuant to <u>Section 9.1.2</u>, then Tenant shall assign and pay
    over to Landlord all insurance proceeds received by or payable to Tenant with respect to damage to the core and shell of the Buildings and structural elements of other improvements situated upon the Premises (but not Tenant Improvements and Tenant&#8217;s
    Personalty). Whether or not Tenant so elects to terminate this Lease, Tenant shall be entitled to any and all of the insurance proceeds payable for the damage to Tenant&#8217;s Personalty.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Waiver</u>. Tenant (for itself and all
    others claiming through Tenant) irrevocably waives and releases its rights to make repairs at Landlord&#8217;s expense. The provisions of this Lease, including this <u>Section 9.2</u>, constitute an express agreement between Landlord and Tenant with respect
    to any damage to, or destruction of, any portion of the Premises. Any law in respect of any rights or obligations concerning any such damage or destruction in the absence of an express agreement between the parties, and any other law relating to damage
    or destruction of leased premises, whether in effect on the date of this Lease or thereafter, shall have no application to this Lease or any damage or destruction of any part of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Total Condemnation</u>. If after the
    execution of this Lease and prior to the expiration of the Term, all or a significant portion of the Premises shall be permanently taken under power of eminent domain by any public or private authority, or conveyed by Landlord to said authority in lieu
    of such taking (collectively, a &#8220;<b>Taking</b>&#8221;), and if as a result of such Taking: (a) access to the Premises to and from the publicly dedicated roads adjacent to the Premises as of the Effective Date is permanently and materially impaired such that
    Tenant no longer has access to such dedicated road; (b) there is insufficient parking to operate the Premises under Applicable Laws and replacement parking cannot be constructed or provided elsewhere on the Premises; or (c) the taking includes a
    portion of the Buildings such that the remaining portions are unsuitable for the Permitted Use and the remaining portions of the Premises cannot, in the reasonable opinion of a contractor mutually agreed upon by Landlord and Tenant, be restored to
    useful condition within eighteen (18) months after the Taking (such event, a &#8220;<b>Total Condemnation</b>&#8221;), then, in such event:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>. On the date of the Total
    Condemnation, this Lease shall automatically terminate; <u>provided</u>, <u>however</u>, that Tenant&#8217;s obligations under any indemnification provisions of this Lease and Tenant&#8217;s obligation to pay Rent and all other monetary obligations (whether
    payable to Landlord or a third party) accruing under this Lease prior to the date of termination shall survive such termination. If the date of such Total Condemnation is other than the first day of a month, the Base Rent for the month in which such
    Total Condemnation occurs shall be apportioned based on the date of the Total Condemnation</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">9.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Award</u>. Landlord shall be entitled to
    receive the entire award payable in connection with a Total Condemnation without deduction for any estate vested in Tenant by this Lease, and Tenant hereby expressly assigns to Landlord all of its right, title and interest in and to every such award
    and agrees that Tenant shall not be entitled to any such award or other payment for the value of Tenant&#8217;s leasehold interest in this Lease; <u>provided</u>, <u>however</u>, that Tenant shall have the right to file any separate claim available to
    Tenant for any taking of Tenant's Personalty, loss of goodwill, and for moving and relocation expenses (but only if such payment to Tenant does not reduce any award available to Landlord).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Partial Condemnation</u>. In the event
    of a Taking which is not a Total Condemnation, neither party shall have the right to terminate this Lease and Landlord shall, using proceeds therefor from the condemning authority, restore the core and shell of the Buildings and structural elements of
    other improvements situated upon the Premises reasonably sufficient to make a functional unit of the remaining portion of the Premises, and Tenant shall proceed with restoration of the Tenant Improvements to the extent possible to make a functional
    unit of the remaining portion of the Premises. In the event any partial taking materially affects Tenant&#8217;s operations in the Buildings for the Permitted Use, such that the Premises no longer provides sufficient space for Tenant to carry out its
    business without material interference with the Permitted Use, then, commencing on the date on which Tenant&#8217;s operations are materially affected, the Base Rent shall be abated in proportion to the square footage of the portion of the Buildings taken.</p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 10<br>
    MISCELLANEOUS</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: -0.2pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Notices</u>. Any notice, consent, demand,
    or other communication or document required or permitted to be given under this Lease or pursuant to any law (&#8220;<b>Notice(s)</b>&#8221;), shall be (a) in writing (except as otherwise provided in this Lease), (b) addressed to the intended recipient at its
    address set forth in the Basic Lease Information (provided that each of Landlord and Tenant may change its addresses for the giving of notices by giving written notice thereof to the other party), (c) sent by fully prepaid registered or certified
    United States Mail return receipt requested, or by any nationally recognized overnight courier service furnishing a written record of attempted or actual delivery, and (d) deemed to have been delivered upon actually delivery or rejection of delivery.
    Any Notice may be given by an attorney on behalf of Landlord or Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">10.2</td>
        <td style="text-align: justify"><u>Certain Representations</u></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>Neither of Tenant nor any wholly-owned subsidiary
    of Tenant is (i) in violation of any OFAC Law or Regulation, the U.S. Patriot Act or Anti-Corruption Legislation, (ii) is named by any Executive Order (including the September 23, 2001, Executive Order Blocking Property and Prohibiting Transactions
    With Persons Who Commit, Threaten to Commit, or Support Terrorism) or the United States Treasury Department as a terrorist, &#8220;Specially Designated National and Blocked Person,&#8221; or (iii) (to the Tenant&#8217;s knowledge) acting, directly or indirectly, on
    behalf of any such person. To Tenant&#8217;s actual knowledge, no such person, group, entity or nation owns 20% or more Tenant&#8217;s voting securities. To the Tenant&#8217;s knowledge, the monies used in connection with this Agreement and amounts committed with
    respect thereto, were not and are not derived from any activities that contravene any applicable OFAC Laws and Regulations, the U.S. Patriot Act, AML Legislation or Anti-Corruption Legislation, each as defined below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>As used herein, the term &#8220;<b>AML Legislation</b>&#8221;
    means United States anti-money laundering-related and anti-terrorism financing laws, regulations, and codes of practice applicable to the Tenant, its affiliates, and their operations from time to time, including, any regulations, guidelines or orders
    thereunder. As used herein, the term &#8220;<b>Anti-Corruption Legislation</b>&#8221; means U.S. Foreign Corrupt Practices Act and similar anticorruption and anti-bribery laws of the United States. As used herein, the term &#8220;<b>OFAC Laws and Regulations</b>&#8221; means
    (i) any lists, laws, rules, sanctions and regulations maintained by OFAC pursuant to any authorizing statute, Executive Order or regulation, including the Trading with the Enemy Act, 50 U.S.C. App. &#167; 1 et seq., the International Emergency Economic
    Powers Act, 50 U.S.C. &#167; 1701 et seq., the Iraq Sanctions Act, Pub. L. 101-513, Title V, &#167;&#167; 586 to 586J, 104 Stat. 2047, the National Emergencies Act, 50 U.S.C. &#167;&#167; 1601 et seq., the Antiterrorism and Effective Death Penalty Act of 1996, Pub. L. 104-
    132, 110 Stat. 1214-1319, the United Nations Participation Act, 22 U.S.C. &#167; 287c, the International Security and Development Cooperation Act, 22 U.S.C. &#167; 2349aa-9, the Nuclear Proliferation Prevention Act of 1994, Pub. L. 103-236, 108 Stat. 507, the
    Foreign Narcotics Kingpin Designation Act, 21 U.S.C. &#167;&#167; 1901 et seq., the Iran and Libya Sanctions Act of 1996, Pub. L. 104-172, 110 Stat. 1541, the Cuban Democracy Act, 22 U.S.C. &#167;&#167; 6001 et seq., the Cuban Liberty and Democratic Solidarity Act, 22
    U.S.C. &#167;&#167; 6021-91, and the Foreign Operations, Export Financing and Related Programs Appropriations Act, 1997, Pub. L. 104-208, 110 Stat. 3009-172; (ii) all regulations, executive orders, or administrative orders of any kind issued under these
    statutes, including 31 C.F.R., Subtitle B, Chapter V; and (iii) any other applicable United States civil or criminal federal or state laws, regulations, or orders that (1) limit the use of and/or seek the forfeiture of proceeds from illegal
    transactions; (2) limit commercial transactions with designated countries or individuals believed to be terrorists, narcotics dealers or otherwise engaged in activities contrary to the interests of the United States; or (3) are designed to disrupt the
    flow of funds to terrorist organizations, as all of the foregoing laws may be amended from time to time.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Brokers</u>. Each of Landlord and Tenant
    represents and warrants to the other that such party has not dealt with any broker or finder in connection with this Lease. Each party shall indemnify the other and hold it harmless from any cost, expense, or liability (including costs of suit and
    reasonable attorneys&#8217; fees) for any compensation, commission or fees claimed by any other real estate broker or agent in connection with this Lease or its negotiation by reason of any act or statement of the indemnifying party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No Waivers</u>. No provision of this Lease
    shall be deemed waived by either party unless expressly waived in a writing signed by the waiving party (and then only to the extent so expressly waived). No waiver shall be implied by delay or any other act or omission of either party. No waiver by
    either party of any provision of this Lease shall be deemed a waiver of such provision with respect to any subsequent matter relating to such provision, and Landlord&#8217;s consent or approval respecting any action by Tenant shall not constitute a waiver of
    the requirement for obtaining Landlord&#8217;s consent or approval respecting any subsequent action. No act or thing done by Landlord or its agents during the Term shall be deemed a termination of this Lease, an acceleration of the Termination Date, or an
    acceptance of the surrender of the Premises, and no agreement to terminate this Lease, accelerate the Termination Date, or accept a surrender of the Premises shall be valid, unless expressly provided in a writing signed by Landlord. Acceptance of the
    full or any partial payment of Rent shall not be deemed Landlord&#8217;s waiver of any breach by Tenant of any provision of this Lease and Landlord&#8217;s acceptance of a lesser amount than the Rent due under this Lease shall not be deemed Landlord&#8217;s waiver of
    Landlord&#8217;s right to receive the full amount of Rent due, nor shall any endorsement or statement on any check or payment or any letter accompanying such check or payment be deemed an accord and satisfaction, and Landlord may accept such partial payment
    without prejudice to Landlord&#8217;s right to recover the full amount of Rent due. Tenant acknowledges that this <u>Section 10.4</u> imparts actual notice to Tenant that Landlord&#8217;s acceptance of partial payment of Rent does not constitute a waiver of any
    of Landlord&#8217;s rights, including any right Landlord may have to recover possession of the Premises. Forbearance by Landlord in enforcing one or more of the remedies provided in this Lease upon an Event of Default shall not be deemed a waiver of such
    Event of Default or of Landlord&#8217;s right to enforce any such remedies with respect to such Event of Default or any subsequent Event of Default. Landlord&#8217;s acceptance of any Rent or of the performance of any other provision of this Lease from any person
    other than Tenant, including any Transferee, shall not be deemed a waiver of Landlord&#8217;s right to approve any Transfer in accordance with <u>Article 5</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Future Development</u>. Provided the
    Tenant is Ionis Pharmaceuticals, Inc., or an affiliate, and Tenant is operating for the Permitted Use, in no event shall Landlord take any action or permit any actions to be taken that may or will increase or decrease, modify, change or alter the
    zoning or entitlements of the Premises, alter the Buildings, change the site amenities, or add additional improvements without the express written consent of Tenant. Notwithstanding the foregoing, subject to the terms of this Section 10.5, Landlord
    reserves all rights as may be necessary or desirable to construct additional improvements serving the Premises, the Companion Premises, or both, in connection with the construction of the improvements under the Companion Lease, including, without
    limitation, pedestrian walkways, installation of utilities and utility connections, structured parking, a pedestrian bridge, and site improvements at the Premises, and to modify the Buildings in connection with any such additional development, all as
    required by the Companion Lease and consistent with the plans and specifications for the construction of the Companion Premises (&#8220;<b>Future Development</b>&#8221;). In connection with any such Future Development, facilities at the Premises may be eliminated,
    altered, or relocated and may also be utilized to serve the Companion Premises. The rights set forth above shall include rights to use portions of the Premises for the purpose of temporary construction staging and related activities and to implement
    valet parking for reserved and unreserved parking spaces for the purpose of facilitating construction during such activities.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">44</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.5.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>Landlord and its representatives, contractors,
    agents, employees and licensees shall have the right during any construction period to enter the Premises to undertake such work; to shore up the foundations, walls, and other improvements at the Premises; to erect scaffolding and protective barricades
    around the Premises; and to do any other act necessary for the safety of the improvements at the Premises or the expeditious completion of such construction. Landlord shall use reasonable efforts not to interfere with the conduct of Tenant&#8217;s business
    and to minimize the extent and duration of any inconvenience, annoyance or disturbance to Tenant resulting from any work pursuant to this Section in or about the Premises, consistent with accepted construction practice, and so long as Landlord uses
    such reasonable efforts Landlord shall not be liable to Tenant for any compensation or reduction of Rent by reason of inconvenience or annoyance or for loss of business resulting from any act by Landlord pursuant to this Section.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.5.2&#160;&#160;<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>Tenant agrees to enter into any instruments
    reasonably requested by Landlord in connection with the Future Improvements, and for the continued maintenance of such Future Improvements, so long as the same do not materially decrease the rights or materially and adversely increase the obligations
    of Tenant under this Lease, including reciprocal easement agreements, declarations of covenants, and other agreements to facilitate use of the improvements between the Premises and Companion Premises. Tenant agrees not to take any action to oppose any
    application by Landlord for any permits, consents or approvals from any governmental authorities for any redevelopment or additional development of all or any part of the Companion Premises, and will use all commercially reasonable efforts to prevent
    any of Tenant&#8217;s subtenants or assigns, and Tenant&#8217;s and their respective officers, directors, employees, agents, contractors and consultants from doing so. For purposes hereof, action to oppose any such application shall include, without limitation,
    communications with any governmental authorities requesting that any such application be limited or altered. Also for purposes hereof, commercially reasonable efforts shall include, without limitation, commercially reasonable efforts, upon receiving
    notice of any such action to oppose any application on the part of any Tenant Parties, to obtain injunctive relief, and, in the case of a subtenant, exercising remedies against the subtenant under its sublease.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  </div>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">10.6</td>
        <td style="text-align: justify"><u>Other Provisions</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Covenant of Quiet Enjoyment</u>. Landlord
    covenants that Tenant, while no Event of Default has occurred and be continuing, shall peaceably and quietly have, hold, and enjoy the Premises for the Term without hindrance from Landlord, but not otherwise, subject to all matters of record and to the
    terms and provisions of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Survival</u>. All obligations of Tenant under
    this Lease not fully performed as of the Termination Date shall survive the Termination Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Entire Agreement</u>. This Lease, together
    with the Exhibits, contains all of the agreements of Landlord and Tenant in respect of this Lease and supersedes any previous negotiations. There have been no representations made by Landlord or any of Landlord&#8217;s representatives, or understandings made
    between Landlord and Tenant, other than those set forth in this Lease and the Exhibits. This Lease may not be modified except by a written instrument duly executed by the party to be bound. Landlord and Tenant each represent to the other, that is has
    the individuals executing this Lease have been properly authorized by proper action of the Landlord and Tenant, as the case may be.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Execution in Counterparts</u>. This Lease may
    be executed in counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same instrument.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Recording</u>. Tenant shall not record this
    Lease, but may record a short form memorandum of this Lease in the form attached hereto as <u>Exhibit D</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Non-Discrimination</u>. Tenant shall not (and
    Tenant shall not permit any person claiming through or under Tenant to) discriminate against or segregate any person or group of persons on account of race, color, creed, sex, religion, marital status, ancestry, or national origin, whether in the use,
    occupancy, subleasing, transferring, or enjoyment of the Premises, or otherwise.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Attorneys&#8217; Fees</u>. In any action or
    proceeding that Landlord or Tenant initiates against the other party declaratory or otherwise, arising out of this Lease, the unsuccessful party in such action or proceeding shall reimburse the prevailing party for its costs, including reasonable
    attorneys&#8217; fees (at trial and appellate levels).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Waiver of Consequential Damages</u>. Except as
    set forth in <u>Section 1.3</u> and <u>Section 3.3</u>, neither Landlord nor Tenant shall be liable to the other for any form of special, indirect, consequential, or punitive damages.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Tenant Information</u>. Upon Landlord&#8217;s
    request from time to time, Tenant shall provide to Landlord the financial statements for Tenant for its most recent fiscal year and fiscal quarter. Financial statements for each fiscal year shall be prepared and certified by a certified public
    accountant; financial statements for each quarter shall be prepared and certified by Tenant&#8217;s chief financial officer. In addition, if so requested, and provided that Landlord may not require such information more than once in any calendar year except
    where Landlord has reasonable grounds for concern, details of the financial and credit standing and details of the corporate organization of Tenant and any Indemnitor, including copies of financial statements for the last three (3) fiscal years of
    Tenant. If requested by Tenant, such financial statements shall be furnished pursuant to a confidentiality agreement in a form reasonably provided by Landlord for such purpose. The provisions of this Section 10.6.9 shall not apply to Tenant if it is a
    Public Company and its financial statements are publicly available.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">46</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.6.10<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;</font><u>REIT Provisions</u>. Tenant and Landlord intend
    that all amounts payable by Tenant to Landlord shall qualify as &#8220;rents from real property,&#8221; and will otherwise not constitute &#8220;unrelated business taxable income&#8221; or &#8220;impermissible tenant services income,&#8221; all within the meaning of Section 856(d) of the
    Internal Revenue Code of 1986, as amended (the &#8220;<b>Code</b>&#8221;) and the U.S. Department of Treasury Regulations promulgated thereunder (the &#8220;<b>Regulations</b>&#8221;). In the event that Landlord determines that there is any risk that any amount payable under
    this Lease may not qualify as &#8220;rents from real property&#8221; or will otherwise constitute impermissible tenant services income within the meaning of Section 856(d) of the Code and the Regulations, Tenant agrees to (a) cooperate with Landlord by entering
    into such amendment or amendments as Landlord deems necessary to qualify all amounts payable under this Lease as &#8220;rents from real property&#8221; and (b) permit (and, upon request, to acknowledge in writing) an assignment of the obligation to provide certain
    services under the Lease, and, upon request, to enter into direct agreements with the parties furnishing such services (which shall include but not be limited to a taxable REIT subsidiary of Landlord). Notwithstanding the foregoing, Tenant shall not be
    required to take any action pursuant to the preceding sentence (including acknowledging in writing an assignment of services pursuant thereto) if such action would result in (A) Tenant&#8217;s incurring more than de minimis additional liability under this
    Lease or (B) more than a de minimis negative change in the quality or level of Buildings operations or services rendered to Tenant under this Lease. For the avoidance of doubt, (i) if Tenant does not acknowledge in writing an assignment as described in
    clause (b) above (it being agreed that Tenant shall not unreasonably withhold, condition or delay such acknowledgment so long as the criteria in clauses (A) and (B), above, are satisfied), then Landlord shall not be released from liability under this
    Lease with respect to the services so assigned; and (ii) nothing in this Section 10.6.10 shall limit or otherwise affect Landlord&#8217;s ability to assign its entire interest in this Lease to any party as part of a conveyance of Landlord&#8217;s ownership
    interest in the Buildings.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">10.7</td>
        <td style="text-align: justify"><u>Interpretation</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Captions</u>. The captions in this Lease are
    for convenience of reference and shall not define, increase, limit, or describe the scope or intent of any provision of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font><u>Landlord and Tenant</u>. The terms &#8220;Tenant&#8221; and
    &#8220;Landlord&#8221;, and any pronoun used in place thereof, shall indicate and include each of the parties&#8217; and respective successors, executors, administrators, and permitted assigns, according to the context, provided that, for the purposes of any provisions
    indemnifying or waiving claims against, Landlord, the term &#8220;Landlord&#8221; shall also include Landlord&#8217;s present and future investment manager, and property management company, and all of their trustees, directors, officers, partners, beneficiaries,
    principals, members, managers, investors, stockholders, employees, Affiliates, agents, representatives, contractors (and subcontractors of any tier), successors and assigns.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Non-Exclusivity</u>. Whenever the words
    &#8220;including&#8221;, &#8220;include&#8221;, or &#8220;includes&#8221; are used in this Lease, they shall be interpreted in a non-exclusive manner as though the words &#8220;without limitation&#8221; immediately followed the same. Any reference to &#8220;any part&#8221; or &#8220;any portion of&#8221; the Premises or
    any other property shall be construed to refer to all or any part of the same.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">47</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Covenants Independent</u>. This Lease shall be
    construed as though the covenants herein between Landlord and Tenant are independent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Joint and Several Liability</u>. In any case
    where either Landlord or Tenant consists of more than one person, the obligations of such party under this Lease shall be joint and several.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.6&#160;&#160;&#160;&#160;&#160; <u>Time of the Essence</u>. Time is of the essence of this Lease and all of its provisions.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.7&#160;&#160;&#160;&#160;&#160; <u>Governing Law</u>. This Lease shall in all respects be governed by the laws of the State of California without
    giving effect to the principles of conflicts of law thereof or of any other jurisdiction that would result in the application of the Applicable Laws of any other jurisdiction. Tenant&#8217;s obligation to pay Rent shall not be discharged or otherwise
    affected by any Applicable Law or regulation now or hereafter applicable to the Premises, or any other restriction on Tenant&#8217;s use, or (except as expressly provided in this Lease) any Casualty or Taking, or any failure by Landlord to perform any
    covenant contained herein, or any other occurrence; and no termination or abatement remedy that is not expressly provided for in this Lease for any breach or failure by Landlord to perform any obligation under this Lease shall be implied or applicable
    as a matter of Applicable Law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160; </font><u>Successors and Assigns</u>. Subject to the
    provisions of <u>Article 5</u>, the provisions of this Lease shall be binding upon and inure to the benefit of the heirs, successors, executors, administrators, and assigns of Landlord and Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">10.7.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Submission</u>. The submission of this Lease
    to Tenant or a summary of some or all of its provisions for examination does not constitute a reservation of or option for the Premises or an offer to lease, and no legal obligations shall arise with respect to the Premises or other matters herein
    unless and until such time as this Lease is executed and delivered by Landlord and Tenant and approved by the holder of any mortgage on the Buildings having the right to approve this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Signage</u>. Tenant shall have
    the right to install such signage at or upon the Premises as permitted by Applicable Laws. Tenant, at its sole expense, shall maintain Tenant&#8217;s Signage in good condition and repair during the Term. Should Tenant&#8217;s Signage require maintenance or repairs
    as determined in Landlord&#8217;s reasonable judgment, Landlord shall have the right to provide notice thereof to Tenant and Tenant shall cause such repairs and/or maintenance to be performed within thirty (30) days after receipt of such notice from Landlord
    at Tenant&#8217;s sole cost and expense. Should Tenant fail to perform such maintenance and repairs within the period described in the immediately preceding sentence, then, in addition to all of Landlord&#8217;s other rights and remedies, Landlord may, but need
    not, perform the required maintenance and repairs, and Tenant shall pay Landlord the cost thereof, plus a fee for Landlord&#8217;s oversight and coordination of such work equal to five percent (5%) of its cost, within thirty (30) days after receipt of
    Landlord&#8217;s request for payment, together with reasonable, supporting backup documentation. Landlord shall have the right to maintain one or more signs at the Premises in a prominent location near the entrance to the Building identifying the property
    manager and the identity of Landlord or its direct or indirect ownership group in a manner similar to that shown on <u>Exhibit G</u> attached, subject to Tenant&#8217;s approval of the size and location of such signage, such approval not to be unreasonably
    withheld, conditioned or delayed.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">48</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Choice of Law</u>. This Lease shall be
    governed by the Applicable Laws of the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.10<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>CASp Inspection</u>. For purposes of Section
    1938(a) of the California Civil Code, Landlord hereby discloses to Tenant, and Tenant hereby acknowledges, that neither the Buildings nor any portion of the Premises has undergone inspection by a Certified Access Specialist (CASp) (defined by
    California Civil Code Section 55.52). Pursuant to California Civil Code Section 1938, Tenant is hereby notified as follows: &#8220;A Certified Access Specialist (CASp) can inspect the subject premises and determine whether the subject premises comply with
    all of the applicable construction-related accessibility standards under state law. Although state law does not require a CASp inspection of the subject premises, the commercial property owner or lessor may not prohibit the lessee or tenant from
    obtaining a CASp inspection of the subject premises for the occupancy of the lessee or tenant, if requested by lessee or tenant. The parties shall mutually agree on the arrangements for the time and manner of any CASp inspection, the payment of the fee
    for the CASp inspection and the cost of making any repairs necessary to correct violations of construction-related accessibility standards within the premises.&#8221; If Tenant requests to perform a CASp inspection of the Premises, Tenant shall, at its cost,
    retain a CASp approved by Landlord to perform the inspection of the Premises at a time agreed upon by the parties. Tenant shall provide Landlord with a copy of any report or certificate issued by the CASp (the &#8220;<b>CASp Report</b>&#8221;). Landlord and Tenant
    agree that any modifications necessary to correct violations of construction related accessibility standards identified in the CASp Report shall be the responsibility of Tenant. Tenant agrees to keep the information in the CASp Report confidential
    except as necessary for the Tenant to complete such modifications.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.11<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Landlord Access</u>. Landlord, its
    affiliates, and their respective contractors and agents, subject to the terms of this Section 10.11, may, (a) at any and all reasonable times during normal business hours (or during non-business hours, if Landlord so requests and Tenant consents), and
    upon at least two (2) business days&#8217; prior notice (which may be oral or by email to the office manager or other Tenant-designated individual at the Premises; but provided that no time restrictions shall apply or advance notice be required if a bona
    fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry and any oral notice will be followed immediately by email notice as provided above prior to entry), enter the Premises to (i) inspect the same
    and to determine whether Tenant is in compliance with its obligations hereunder, (ii) supply any service Landlord is required to provide hereunder, (iii) alter, improve or repair any portion of the premises under the Companion Lease for which access to
    or through the Premises is reasonably necessary, (iv) post notices of non-responsibility, (v) show the Premises to current and prospective investors, lenders and purchasers, and (vii) show the Premises, other than the Secure Access Areas, during the
    final eighteen (18) months of the Term (provided that Tenant has not timely exercised an Extension Option to extend the Term pursuant to Section 1.4) to prospective tenants, and (b) notwithstanding the foregoing, at any and all reasonable times during
    business and non-business hours and upon at least two (2) business days&#8217; prior notice enter the Premises for the purposes of performing any repairs or maintenance that Landlord is obligated or entitled to perform pursuant to this Lease (provided that
    no time restrictions shall apply if a bona fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry); provided, however, that Landlord shall comply with Tenant&#8217;s reasonable safety procedures and
    protocols with respect to the Premises, and with respect to portions of the Premises (if any) that are reasonably designated in writing by Tenant to Landlord as controlled or having restricted access (the &#8220;<b>Secure Access Areas</b>&#8221;), shall comply
    with Tenant&#8217;s reasonable additional security and safety procedures and protocols related to such portions of the Premises including only entering such designated Secure Access Areas when accompanied by a Tenant representative (provided further, that
    Tenant shall provide a Tenant representative to accompany Landlord upon written request from Landlord at least two (2) business days&#8217; in advance). In no event shall Tenant&#8217;s Base Rent abate as a result of Landlord&#8217;s activities pursuant to this Section;
    provided, however, that all such activities shall be conducted in such a manner so as to cause as little interference to Tenant as is reasonably possible. Landlord shall at all times retain keys, key cards and access codes with which to unlock all of
    the doors in the Premises. Landlord acknowledges that the standard operating procedures set forth on <u>Exhibit L</u> shall apply to the issuance to Landlord of any key cards, electronic keypad codes, or door keys to any Secure Access Areas for any
    unaccompanied access too the Premises by Landlord, provided, however, that Tenant shall identify a single designee to act as Landlord&#8217;s point of contact to administer the requirements of Tenant&#8217;s standard operating procedures on behalf of Landlord and
    that in no event shall any such requirements prohibit Landlord&#8217;s entry into Secure Access Areas (i) in the event of a bona fide emergency with an immediate threat to property damage or personal injury that necessitates immediate entry or (ii) when
    accompanied by a representative of Tenant. If an emergency necessitates immediate access to the Premises, Landlord may use whatever force is necessary to enter the Premises, and any such entry to the Premises shall not constitute a forcible or unlawful
    entry to the Premises, a detainer of the Premises, an eviction of Tenant from the Premises or any portion thereof, or a violation of the provisions of this Section 10.11. Notwithstanding anything herein to the contrary, in the event Tenant notifies
    Landlord within one (1) business day (which may be oral or by email to the Landlord-designated individual) following Landlord&#8217;s request for access that the proposed day and/or time for entry will cause a disruption to a planned event, meeting or other
    programming for Tenant, Landlord and Tenant shall cooperate with one another to identify a better date and/or time Landlord&#8217;s entry of the Premises.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">49</font></div>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 11&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>TENANT&#8217;S RIGHT OF FIRST OFFER</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">11.1</td>
        <td style="text-align: justify"><u>Right of First Offer</u>.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>Notwithstanding anything contained in this Lease to
    the contrary, provided that (i) no Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or its affiliate, if Landlord intends to offer the Premises (or any portion thereof) for sale to an
    unaffiliated third party, Landlord shall promptly notify Tenant of the same in writing (the &#8220;<b>Offer Notice</b>&#8221;) and indicate the terms and conditions upon which Landlord is willing to accept for the sale of the Premises to a third party. Tenant may
    elect to purchase the Premises (or portion thereof) on the terms and conditions set forth in the Offer Notice by notifying Landlord in writing (the &#8220;<b>Election Notice</b>&#8221;) of its election no later than fifteen (15) days after the Offer Notice, which
    notice shall be accompanied by the Option Deposit (defined herein), and the sale of the Premises shall be consummated pursuant to the terms hereof on a date (the &#8220;<b>Closing Date</b>&#8221;) within sixty (60) days after the Election Notice, such date to be
    mutually agreed upon by Landlord or Tenant. In the event of any of the following: (x) Tenant fails to deliver the Election Notice or the Option Deposit to Landlord on or before the expiration of the 15-day period set forth above, (y) Tenant fails to
    close on its acquisition of the Premises on or before the Closing Date, or (z) Landlord provides an Offer Notice to Tenant and Tenant does not exercise its right to purchase the Premises, then in each case Tenant shall be deemed to have waived its
    right to purchase the Premises and thereafter Tenant&#8217;s rights under this Article 11 shall be null and void and of no further force or effect. The term &#8220;<b>Option Deposit</b>&#8221; shall mean the amount of cash deposit required in the Offer Notice or, if no
    cash deposit is specified in the Offer Notice, a sum equal to five percent (5%) of the purchase price for the Premises set forth in the Offer Notice.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">50</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>If the Premises is not sold to Tenant pursuant to
    Section 11.1.1 above, Landlord shall have the right to direct the marketing of the Premises (including the unilateral right to select any broker to be utilized), and to take all actions in furtherance thereof, including, without limitation, the right
    and authority to execute, such agreements, documents, instruments and applications, including a purchase and sale agreement and a deed, assignment of leases, bills of sale and other conveyance documents conveying the Premises (collectively, &#8220;<b>Sale
      Documents</b>&#8221;) as Landlord, may reasonably deem necessary or desirable in order consummate such sale, and, subject to <u>Section 11.1.1</u> above and <u>Section 11.2</u> below, Landlord shall be authorized to accept an offer for the sale of the
    Premises. If Landlord modifies the terms of its offer such that the purchase price is less than ninety-five percent (95%) of the consideration provided in the Offer Notice, then the proposed transaction shall again be subject to Tenant&#8217;s rights under
    this Article 11, and Landlord shall deliver an amended Offer Notice to Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>Tenant shall, at no material out-of-pocket cost to
    Tenant, reasonably cooperate with Landlord&#8217;s efforts to sell the Premises, including by providing information with respect to the Premises, and by allowing and facilitating physical access to the Premises to prospective purchasers and their lenders and
    consultants, but such cooperation and execution by the Tenant shall not be a condition to the effectiveness of any actions taken by Landlord with respect to such sale or to the effectiveness of Sale Documents.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Competitors</u>. Provided that
    (i) no Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or an affiliate, and such Tenant remains in possession of the Premises and operating for the Permitted Use, Landlord shall not sell the
    Premises (or any portion thereof, or all or substantially all of Landlord&#8217;s interest therein) or enter into an agreement to that would transfer Landlord&#8217;s interest in the Premises to a Competitor during the Term; provided, however, this Section 11.2
    shall not prohibit Landlord from entering into an agreement to sell or transfer the Premises to a Competitor if the effective date of the transfer would occur after the expiration of the Term. As used herein, &#8220;<b>Competitor</b>&#8221; or &#8220;<b>Competitors</b>&#8221;
    means the companies expressly listed as competitors in Tenant&#8217;s most recent publicly filed Annual Report (10-K); provided, however, (1) such companies shall be directly engaged in the development, manufacturing, or commercializing a medicine or other
    life sciences product, and &#8220;Competitor&#8221; shall not mean any affiliates, investors, parents, or other stake-holders of such companies, and (2) there shall not be more than twenty (20) Competitors at any one time. If Tenant&#8217;s most recent publicly filed
    Annual Report (10-K) includes more than twenty (20) companies that would otherwise be deemed Competitors, only those companies that were previously listed in Tenant&#8217;s Annual Report (10-K) shall be deemed a Competitor unless Tenant provides a written
    notice to Landlord specifying which companies listed in Tenant&#8217;s most recent Annual Report (10-K) shall be included in the list of twenty (20) Competitors for the purposes of this Lease.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">51</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Excluded Transfers</u>. Notwithstanding
    anything to the contrary herein, Tenant&#8217;s rights under this Article 11 shall not apply to any transaction that meets at least one of the following criteria:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>any sale/leaseback transaction made in connection
    with a bona fide financing, provided that the seller/lessee under any such transaction shall be bound by the provisions of this Article 11 at such time, if any, as such seller/lessee reacquires title to the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>any sale or transfer of the Premises to a
    partnership, corporation, limited liability company, trust or other entity that is under control by, common control with, or controls Landlord or any direct or indirect owner of Landlord, but any such transferee shall hold title subject to Tenant's
    rights under this Article 11;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>any transfer in the nature of a financing
    transaction with a financial institution that is made for a bona fide business purpose (i.e., other than in order to allow a transfer of the Premises in avoidance of Tenant's rights under this Article 11), including without limitation the granting of,
    foreclosure under, or giving of a deed-in-lieu of foreclosure under, a mortgage or the granting or exercise of any pledge of ownership interests; provided that, following any foreclosure of the Premises, deed in lieu thereof, or similar acquisition of
    title by a mortgagee, lender, or their affiliates, following the first sale of the Premises by such mortgagee, lender or their affiliates, the subsequent Landlord shall be bound by Tenant&#8217;s rights under this Article 11;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>any issuance or transfer of a direct or indirect
    interest in Landlord that represents a transfer of less than 80% of such interests (so long as such transfer does not also include the ability to control the day-to-day operations of Landlord); provided that any transferee of direct interests in
    Landlord otherwise described in this Section 11.3.4 is not a Competitor;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>any issuance or transfer of a direct or indirect
    interest in Landlord on a nationally recognized stock exchange; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>any bona fide portfolio transaction that includes
    at least two other real estate assets (excluding the Premises and, if the Companion Lease is in effect, the Companion Premises) that in the aggregate have rentable space at least equal to 416,000 square feet.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>. Upon (x) any sale of the
    Premises, (y) any portfolio transaction sale that includes the Premises, or (z) any foreclosure of a Mortgage on the Premises or conveyance by deed-in-lieu of foreclosure, in each case to a third-party person or entity in accordance with the terms of
    this Article 11, Tenant&#8217;s right of first offer to purchase the Premises under this Article 11 shall forever terminate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Confidentiality</u>. Any Offer Notice and
    information in connection therewith, and any information regarding a sale of the Premises, provided to Tenant by Landlord pursuant to this Article 11 shall be held confidential by Tenant and not disclosed to any third party except as required by law or
    in connection with any dispute between Landlord and Tenant regarding this Article 11 and for disclosures to Tenant&#8217;s legal advisors and third-party consultants to the extent such legal advisors and consultants are reasonably required for Tenant to
    evaluate such information and, in each case, provided that such legal advisors and consultants are made subject to the provisions of this paragraph or are otherwise bound by provisional obligations of confidentiality. Any such information shall be
    returned by Tenant to Landlord if Tenant&#8217;s rights under this Article 11 terminate in accordance with the terms hereof. Nothing in this Section 11.5 shall prevent Tenant from making disclosures required by applicable public company disclosure laws,
    provided, however, such disclosures shall include no more information than what is minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to reasonably approve any disclosure that exceeds what is
    minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to review any disclosure prior to the filing of the same for purposes of confirming compliance with the terms of this sentence, to the extent
    that such review is permitted pursuant to Applicable Law.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">52</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 12<br>
    LIMITATION OF LIABILITY</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 46.05pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">12.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Liability</u>. Tenant agrees
    from time to time to look only to Landlord&#8217;s interest in the Premises for satisfaction of any claim against Landlord hereunder or under any other instrument related to the Lease (including any separate agreements among the parties and any notices or
    certificates delivered by Landlord) and not to any other property or assets of Landlord. If Landlord from time to time transfers its interest in the Premises, then from and after each such transfer Tenant shall look solely to the interests in the
    Premises of Landlord&#8217;s transferees for the performance of all of the obligations of Landlord hereunder (or under any related instrument). The obligations of Landlord shall not be binding on any direct or indirect partners (or members, trustees, or
    beneficiaries) of Landlord or of any successor, individually, but only upon Landlord&#8217;s or such successor&#8217;s interest described above. Further, if Landlord is, or one of the parties comprising Landlord is, or the Lease is assigned to, a real estate
    investment trust (&#8220;<b>REIT</b>&#8221;), the parties acknowledge and agree that the obligations of the REIT hereunder and under all documents delivered pursuant hereto (and all documents to which the Lease may be pursuant) or which give effect to, or amend or
    supplement, the terms of the Lease are not personally binding upon any trustee thereof, any registered or beneficial holder of units (a &#8220;<b>Unitholder</b>&#8221;) or any annuitant under a plan of which a Unitholder acts as a trustee or carrier, or any
    officers, employees or agents of the REIT and resort shall not be had to, nor shall recourse or satisfaction be sought from, any of the foregoing or the private property of any of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36.05pt">12.2</td>
        <td style="text-align: justify"><u>Assignment of Rents</u>.</td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.1&#160;&#160;<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>With reference to any assignment by Landlord of
    Landlord&#8217;s interest in this Lease, or the rents payable hereunder, conditional in nature or otherwise, which assignment is made to the holder of a mortgage on property that includes the Premises, Tenant agrees that the execution thereof by Landlord,
    and the acceptance thereof by the holder of such mortgage shall never be treated as an assumption by such holder of any of the obligations of Landlord hereunder unless such holder shall, by notice sent to Tenant, specifically otherwise elect and,
    except as aforesaid, such holder shall be treated as having assumed Landlord&#8217;s obligations hereunder only upon foreclosure of such holder&#8217;s mortgage and the taking of possession of the Premises.</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">53</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>In no event shall the acquisition of Landlord&#8217;s
    interest in the Premises by a purchaser that, simultaneously therewith, leases Landlord&#8217;s entire interest in the Premises back to the seller thereof be treated as an assumption by operation of Law or otherwise, of Landlord&#8217;s obligations hereunder, but
    Tenant shall look solely to such seller-lessee, and its successors from time to time in title, for performance of Landlord&#8217;s obligations hereunder. In any such event, this Lease shall be subject and subordinate to the lease to such purchaser. For all
    purposes, such seller-lessee, and its successors in title, shall be the Landlord hereunder unless and until Landlord&#8217;s position shall have been assumed by such purchaser-lessor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>Except as provided in Section 12.2.2, in the
    event of any transfer of title to the Premises by Landlord, the transferring Landlord shall thereafter be entirely freed and relieved from the performance and observance of all covenants and obligations hereunder, and Tenant shall only look to any
    subsequent party becoming Landlord hereunder the same. Tenant hereby agrees to enter into such agreements or instruments as may, from time to time, be requested in confirmation of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">(SIGNATURES APPEAR ON NEXT PAGE)</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">54</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><b>IN WITNESS WHEREOF</b>, the parties hereto have duly executed this Lease on the day and year first above written.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>LANDLORD:</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>2850 2855 &amp; 2859 GAZELLE OWNER (DE)</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><b>LLC,</b> a Delaware limited liability company</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 3%">By:</td>
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        <td style="width: 50%">&#160;</td>
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  </table>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
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        <td style="width: 50%">&#160;</td>
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      <tr style="vertical-align: top; text-align: left">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>TENANT:</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><b>IONIS PHARMACEUTICALS, INC., </b>a</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 3%">By:</td>
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  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 5%">Name:</td>
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      <tr style="vertical-align: top; text-align: left">
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  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">55</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">EXHIBIT A</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>LEGAL DESCRIPTION OF THE PREMISES</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">TRACT ONE:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">PARCEL 1 OF MINOR SUBDIVISION NO. 2018-0009 IONIS CARLSBAD CAMPUS, IN THE CITY OF CARLSBAD,
      COUNTY OF SAN DIEGO, STATE OF CALIFORNIA ACCORDING TO PARCEL MAP NO. 21705 FILED IN THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY ON AUGUST 1, 2019 AS DOCUMENT NO. 2019- 7000286 OF OFFICIAL RECORDS.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">TRACT TWO:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">INTENTIONALLY DELETED.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">TRACT THREE:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">INTENTIONALLY DELETED.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">TRACT THREE-A:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">INTENTIONALLY DELETED.</font></p>
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  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>EXHIBIT B</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">[RESERVED]</font></p>
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  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">EXHIBIT C</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">FORM OF TENANT ESTOPPEL CERTIFICATE</font></p>
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      20 <u>&#160;&#160;&#160;&#160;&#160;</u>.</font></p>
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      20 <u>&#160;&#160;&#160;&#160;&#160;</u>.</font></p>
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      improvements required to be performed by or paid by Landlord under the Lease have been completed and paid and (ii) there are no unpaid allowances or rental concessions payable or creditable to Tenant which have not been paid or credited in full,
      except as follows: <u> </u><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>.</font></p>
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      presently exercisable defenses or offsets which preclude enforcement of the Lease by Landlord except as follows: <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>.</font></p>
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      Additional Rent, and Taxes have been paid when due through <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>. The current monthly installment of Base Rent is $ <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>.</font></p>
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      granted to Tenant pursuant to Article 11, Tenant does not have any option to purchase or right of first refusal or first offer to purchase the Premises, or any portion thereof, or any interest therein and the only interest of Tenant in such property
      is as the Tenant under the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.&#160;&#160;&#160;&#160; The amount of the Security Deposit held by
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      trust deed holder or prospective purchaser or investor will be relying upon the statements contained herein in making the loan or acquiring the Premises, and in accepting an assignment of the Lease as collateral security, and that receipt by it of
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      company or partnership, each individual executing this Estoppel Certificate on behalf of Tenant hereby represents and warrants that Tenant is a duly formed and existing entity qualified to do business in the State of California, if required by law,
      and that Tenant has full right and authority to execute and deliver this Estoppel Certificate and that each person signing on behalf of Tenant is authorized to do so.</font></p>
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      and regulations, court orders, governmental directives and governmental orders and all interpretations of the foregoing.</font></p>
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      deemed to amend, modify or alter the Lease and in the event of any conflict between the Lease and this Estoppel Certificate, the Lease shall prevail. This Estoppel Certificate is delivered in good faith and shall not subject Tenant or the individual
      signatory to any liability (other than estoppel effect) for any purpose, including, without limitation, damages for inaccuracies, errors or omissions, except to the extent resulting from fraud or an intentional and material misstatement of fact.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><i>[Remainder of page intentionally left blank]</i></font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">59</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Executed at <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>&#160;on the <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </u>day of
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    months prior to the expiration of the initial Term or the then-current Renewal Term.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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        <td style="text-align: justify; width: 10%"> [SEAL]</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Morrison &amp; Foerster LLP</font><br>
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"><font style="color: Black"><b><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></b></font></p>
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        Instrument</u>&#8221;) granted by Landlord to Agent, for the benefit of the Lenders, and recorded in the official records of San Diego County, California, which constitutes a first lien against the real property described on <u>Schedule A</u> attached
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      any portion thereof) is and shall be subject and subordinate to the Security Instrument and to all present and future advances under the obligations secured thereby and all renewals, amendments, modifications, consolidations, replacements and
      extensions thereof, to the full extent of the principal amount and other sums secured thereby and interest thereon, so that at all times the Security Instrument shall be and remain a lien on the Property prior to and superior to the Lease for all
      purposes, subject to the provisions set forth in this Agreement. Such subordination shall have the same force and effect as if the Security Instrument and such renewals, modifications, consolidations, replacements and extensions of the Security
      Instrument had been executed, acknowledged, delivered and recorded prior to the Lease, all amendments or modifications of the Lease, and any notice of the Lease.</font></p>
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      (i) Agent (including for this purpose any transferee or nominee of Agent), whether as mortgagee in possession or otherwise; or (ii) any purchaser at a foreclosure sale under the Security Instrument; or (iii) any transferee that acquires possession of
      or title to the Property (whether by acceptance of a deed in lieu of foreclosure or otherwise); or (iv) any successors and assigns of such purchasers and/or transferees (each of the foregoing persons or entities described in clauses (i) through (iv)
      above, a &#8220;<u>Successor</u>&#8221;), as its landlord for the unexpired balance (and any extensions, if exercised) of the term of the Lease upon the terms and conditions set forth in the Lease (as affected by this Agreement), and Tenant shall pay and perform
      in favor of Successor all of the obligations of Tenant under the Lease as if Successor were the original lessor under the Lease. Such attornment shall be effective and self- operative without the execution of any further instruments by any party
      hereto; <u>provided</u>, <u>however</u>, that Tenant will, upon request by Agent or any Successor, execute a reasonable written agreement attorning to Agent or such Successor, which agreement shall, in any event, be subject to the terms and
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Assignment of Leases</b>. Tenant acknowledges that
      it has been advised that Landlord has assigned the Lease and the rents thereunder to Agent, for the benefit of the Lenders, pursuant to the Security Instrument. Tenant acknowledges that the interest of the Landlord under the Lease is to be assigned
      to Agent solely as security for the purposes specified in the Security Instrument, and, on account of the Security Instrument, Agent shall have no duty, liability or obligation whatsoever under the Lease or any extension or renewal thereof, either by
      virtue of the Security Instrument or by any subsequent receipt or collection of rents thereunder, unless Agent shall specifically undertake such liability in writing. The foregoing agreement by Tenant shall not adversely affect any rights of Tenant
      under the Lease with respect to the Landlord in the event of nonperformance by Landlord, subject to the terms of this Agreement. Tenant agrees that if Agent, pursuant to the Security Instrument, and whether or not it becomes a mortgagee in
      possession, shall give written notice to Tenant that Agent has elected to require Tenant to pay to Agent the rent and other charges payable by Tenant under the Lease, Tenant shall (without any duty to inquire as to the enforceability or validity of
      Agent&#8217;s notice) until Agent shall have canceled such election in writing, thereafter pay to Agent all rent and other sums payable under the Lease and such payments to Agent shall be treated as payments made under the Lease. Any such payment shall be
      made notwithstanding any right of setoff, defense or counterclaim which Tenant may have against Landlord, or any right to terminate the Lease. Landlord authorizes and directs Tenant to immediately and continuously make all such payments at the
      direction of Agent, releases Tenant of any and all liability to Landlord for any and all payments so made, and agrees that payments actually made by Tenant to Agent shall be credited towards the amounts due under the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Limitation of Liability</b>. In the event that Agent
      (including for this purpose any transferee or nominee of Agent) or any other Successor succeeds to the interest of Landlord under the Lease, or title to the Property, then none of Agent, any Lender or any Successor shall be: (i) liable in any way to
      Tenant for any act or omission, neglect or default on the part of any prior landlord under the Lease; <u>provided</u>, that, nothing in this clause being deemed to relieve Agent or any Successor of an ongoing default on the part of Landlord with
      respect to repair and maintenance of the Premises that first arose prior to such succession, provided that Tenant notified Agent of such default in accordance with Section 7 of this Agreement and Agent failed to cure same, and Agent or any Successor
      shall have the obligation to cure such ongoing repair and maintenance defaults on the part of Landlord that continue from and after Successor succeeds to the rights of Landlord under the Lease, regardless of when such default or obligation from
      arose, provided that Tenant notified Agent of such default in accordance with Section 7 of this Agreement and Agent failed to cure same; (ii) responsible for any monies (including security deposits) owing by or on deposit with (or any letter of
      credit on deposit with) Landlord to the credit of Tenant (except to the extent any such deposit or letter of credit is actually received by Agent or such Successor, as applicable); (iii) subject to any defense, counterclaim or setoff which
      theretofore accrued to Tenant against any prior landlord; provided, however, that the foregoing shall not limit Tenant&#8217;s right to exercise against Agent or such Successor any offset right otherwise available to Tenant because of events occurring
      after the date of succession and attornment; (iv) bound by any termination, amendment or modification, or assignment/subletting of the Lease after the date hereof (unless Agent expressly approved in writing such termination, amendment or
      modification, or assignment or subletting or the same does not require the Agent&#8217;s approval pursuant to the terms of the Loan Agreement) of the Lease (provided that, (A) as it relates to any assignments/subletting of Lease undertaken in connection
      with the terms and provisions set forth in the Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (B) no such approval shall be required with respect to amendments solely evidencing the exercise of Tenant&#8217;s
      option to extend the Lease and assignments or sublets that do not require the consent of the Landlord pursuant to the terms of the Lease); (v) bound by any previous prepayment of rent for more than one (1) month of the date due, which was not
      approved in writing by Agent; (vi) required after a fire, casualty or condemnation of the Property or Premises to repair or rebuild the same to the extent that such repair or rebuilding requires funds in excess of the insurance or condemnation
      proceeds specifically allocable to the Premises and arising out of such fire, casualty or condemnation which have actually been received by Agent, and then only to the extent required by the terms of the Lease (Agent acknowledging that the exercise
      by Tenant of its remedies pursuant to Article 9 of the Lease are unaffected by the provisions of this clause (vi)), (vii) be liable for or incur any obligation with respect to any representations or warranties made by Landlord under the Lease; (viii)
      liable beyond Agent&#8217;s, such Lender&#8217;s, or such Successor&#8217;s, as applicable, interest in the Property and in the rents, proceeds and profits therefrom; or (ix) responsible for any obligation of Landlord to undertake or complete any work or fund any
      allowance for tenant improvements.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">67</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Purchase Rights</b>. Each of the parties hereto
      acknowledges that pursuant to the Lease, Tenant holds a right of first offer to purchase the property pursuant to Article 11 of the Lease (the &#8220;<u>Purchase Rights</u>&#8221;). The parties hereto agree that the Purchase Rights shall remain valid and in full
      force and effect, but subject and subordinate to the lien(s) of the Security Instrument. In the event that Agent or a Successor succeeds to the interest of Landlord under the Lease, such Purchase Rights shall not be extinguished by a Foreclosure;
      provided, however, that Agent or Successor shall not be bound to the Purchase Rights, and such Purchase Rights shall not apply, with respect to (i) a Foreclosure, including, without limitation, the granting of, foreclosure under, or giving of a
      deed-in-lieu of foreclosure under, a mortgage or the granting or exercise of any pledge of ownership interests, or (ii) the first subsequent sale of the Property following Agent&#8217;s or Successor&#8217;s acquisition of title to the Property, but thereafter
      any, successor landlord to Agent or such Successor shall be bound by such Purchase Rights in accordance with the terms of the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Right to Cure Defaults</b>. Tenant agrees to give to
      Agent, either by certified U.S. mail (return receipt requested) or overnight courier service (i.e., FedEx), a duplicate of each notice of any default by Landlord under the Lease at the time Tenant gives such notice to Landlord, specifying the nature
      of such default, and thereupon Agent shall have the right (but not the obligation) to cure such default, and Tenant shall not exercise its remedies under the Lease unless the Tenant first gives such notice to Agent and provides Agent with notice of
      such default, and an opportunity to cure the same within a period of time that shall be not less than the period of thirty (30) days beyond any period afforded to the Landlord to cure the default under the provisions of the Lease, and a reasonable
      period of time in addition thereto (i) if the circumstances are such that said default cannot reasonably be cured within such period and Agent has commenced and is diligently pursuing such cure, plus (ii<b>)</b> a reasonable period (not to exceed 270
      days unless the cure cannot be effected without Agent taking possession of the Property) during any litigation or enforcement action or proceeding, including a foreclosure, bankruptcy, reorganization, possessory action or a combination thereof
      provided that Agent or any Successor provides Tenant with written notice of its intent to cure such default and then proceeds diligently to cure Landlord&#8217;s default upon acquiring possession of the Premises. It is specifically agreed that Tenant shall
      not exercise its remedies under the Lease against Agent or any Successor for failure to cure any bankruptcy, insolvency or reorganization default on the part of Landlord, any breach by Landlord of any representation or warranty, or any other breach
      or default under the Lease that is personal to Landlord or otherwise not reasonably susceptible of cure by Agent or such Successor. Tenant shall accept performance by Agent of any term, covenant, condition or agreement to be performed by Landlord
      under the Lease with the same force and effect as though performed by Landlord. Without limitation on the foregoing, if the Lease is terminated for any reason other than (a) a termination which is effected unilaterally by Tenant in accordance with
      the express terms of the Lease, (b) the expiration of the term of the Lease, or (c) a termination that occurs in compliance with this Agreement, then upon Agent&#8217;s written request given within thirty (30) days after Agent receives written notice of
      such termination, Tenant shall, within fifteen (15) days after such request, execute and deliver to Agent a new lease of the Premises for the remainder of the term of the Lease, such new lease to be upon all of the same terms, covenants and
      conditions of the Lease applicable to the remainder of the term of the Lease (as affected by this Agreement).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">68</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 0in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant&#8217;s Agreements</b>.
      Tenant hereby represents, warrants, covenants and agrees that: (i) Tenant shall not pay any rent under the Lease more than one month in advance of the date due except as expressly required in the Lease with respect to security deposits, operating
      expenses, taxes and the like; (ii) Tenant shall have no right to appear in any Foreclosure action under the Security Instrument (unless named by Agent in such action, Agent agreeing however not to name Tenant unless required pursuant to applicable
      laws, and then only for such purposes); (iii) Tenant shall not amend or modify, or assign or sublet, the Lease and Tenant shall have no right to cancel or terminate the Lease, without Agent&#8217;s prior written consent (provided that, (x) as it relates to
      any assignments/subletting of Lease undertaken in connection with the terms and provisions set forth in the Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (y) no such approval shall be required with
      respect to amendments solely evidencing the exercise of Tenant&#8217;s option to extend the Lease and assignments or sublets that do not require the consent of the Landlord pursuant to the terms of the Lease), and any attempted amendment or modification,
      assignment or subletting, cancellation or termination of the Lease in violation of the foregoing shall be of no force or effect as to Agent; (iv) Tenant shall not subordinate the Lease to any lien or encumbrance (other than the Security Instrument)
      without Agent&#8217;s prior written consent; (v) except as expressly set forth in Section 6, above, Tenant has no right or option of any nature whatsoever, whether pursuant to the Lease or otherwise, to purchase the Property, or any portion thereof or any
      interest therein, and to the extent that Tenant hereafter acquires any such additional rights or options, the same is hereby acknowledged to be subject and subordinate to the Security Instrument and is hereby waived and released as against Agent and
      any Successor, (vi) Tenant shall promptly, to the same extent and within the same time period required by the Lease, deliver to Agent, from time to time, a written estoppel statement in the form, and with the certifications, required by the Lease;
      (vii) this Agreement supersedes and satisfies any requirement in the Lease relating to the granting of a non-disturbance agreement or providing for subordination of the Lease; (viii) Tenant is the sole owner of the leasehold estate created by the
      Lease; (ix) the interest of Landlord under the Lease is assigned to Agent solely as security for the obligations secured by the Security Instrument, and neither Agent nor the Lenders shall have any duty, liability or obligation under the Lease or any
      extension or renewal thereof, unless Agent either (a) specifically undertakes such liability in writing, or (b) subject to the express terms of this Agreement, Agent becomes a Successor; (x) if this Agreement conflicts with the Lease, then this
      Agreement shall govern as between the parties and any Successor, including upon any attornment pursuant to this Agreement; and (xi) upon Agent&#8217;s transfer or assignment of Agent&#8217;s interests in the Loan, the Lease (or any new lease executed pursuant to
      this Agreement), or the Property, Agent shall be deemed released and relieved of any obligations under this Agreement, the Lease (or any new lease executed pursuant to this Agreement), and with respect to the Property.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">69</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify;"><font style="font-family: Times New Roman,Times,serif; font-size: 10pt;"><b>9.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Authority</b>. Each of Landlord, Agent, and Tenant
      warrants and represents to the other parties hereto that it has duly executed and delivered this Agreement and that the execution, delivery and performance by it of this Agreement (i) are within the its powers, (ii) have been duly authorized by all
      requisite action, and (iii) do not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which it is a party or by which it or any of its property is bound.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 36pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>10.</b></font></td>
        <td style="text-align: justify; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Miscellaneous.</b></font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 10.1</b> The provisions hereof shall be
      binding upon and inure to the benefit of Tenant and Agent and their respective successors and assigns, the term &#8220;Agent&#8221; as used herein includes any successor or assign of the named Agent herein, and the terms &#8220;Tenant&#8221; and &#8220;Landlord&#8221; as used herein
      include any successor and assign of the named Tenant and Landlord herein, respectively; provided, however, that such reference to Tenant&#8217;s or Landlord&#8217;s successors and assigns shall not be construed as Agent&#8217;s consent to any assignment or other
      transfer by Landlord in any instance where Agent&#8217;s consent to such assignment or transfer is required hereunder, under the Security Instrument or under any other document executed in connection therewith.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 10.2</b> Any notices, demands or
      requests to be given under this Agreement shall be in writing and shall be deemed sufficiently given if served personally or upon the first to occur of receipt or the refusal of delivery if mailed by United States certified mail, return receipt
      requested, postage prepaid, or if sent by prepaid Federal Express or other similar overnight delivery service which provides a receipt, addressed to the Primary Address of Landlord, Tenant or Agent set forth below, along with copies to the applicable
      Supplemental Addresses set forth below, or such other address as such party may specify in writing from time to time;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>If to Tenant</u></b>:1</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Primary Address</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font: 10pt Times New Roman, Times, Serif"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Supplement Addresses</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red; margin-left: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u></font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"></p>
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    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 25%">&#160;</div>
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1 NTD: Tenant contact info to be provided</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">70</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: justify">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">PARCEL 1 OF MINOR SUBDIVISION NO. 2018-0009 IONIS CARLSBAD CAMPUS, IN THE CITY OF CARLSBAD,
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      occupy the Property pursuant to the Lease), including, without limitation, Trade Secret Information, any information that would reasonably be considered non-public, confidential or proprietary given the nature of the information and the Ionis
      Parties&#8217; businesses and all notes, analyses and other materials prepared by or for the Purpose that contain any of the foregoing. As used in this Agreement, &#8220;<b><i>Trade Secret Information</i></b>&#8221; means all information that is unique to Ionis&#8217;
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      to, and not being readily ascertainable by proper means by, other persons who can obtain economic value from its disclosure or use; and (ii) is the subject of efforts that are reasonable under the circumstances to maintain its secrecy. The Ionis
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  <p style="text-align: justify; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> <font style="font: 10pt Times New Roman, Times, Serif">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font> <font style="font: 10pt Times New Roman, Times, Serif"><u>Confidential Information and Other Property of the </u>Ionis <u>Parties</u>. All Confidential Information shall be deemed the property of the Ionis Parties. All information, documents, and electronic media (including, but not
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        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.</font></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Prospective Purchaser Obligations</u>. Prospective Purchaser shall:</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not use the Confidential Information,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not disclose the Confidential
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      (ii) are informed by Prospective Purchaser of the confidential nature of the Confidential Information (each an &#8220;<b><i>Authorized Party</i></b>&#8221;) (Prospective Purchaser acknowledging that a breach of this Agreement by a PTP Party shall be treated as a
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      Parties that happen to be in Prospective Purchaser&#8217;s possession;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      be accompanied by an authorized representative of Ionis and not attempt to access areas of the Property without being accompanied by such authorized representative unless Ionis provides its express written consent to access without being accompanied;
      and</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the performance of its obligations
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        Warranties; Disclaimer of Liability</u>. The Ionis Parties make no representation or warranty, express or implied, as to the accuracy or completeness of the Confidential Information disclosed to Prospective Purchaser hereunder. The Ionis Parties
      shall not be liable to Prospective Purchaser for any losses relating to or resulting from the Prospective Purchaser&#8217;s use of any of the Confidential Information or any errors therein or omissions therefrom.</font></p>
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      Notwithstanding anything to the contrary herein, Prospective Purchaser may disclose certain Confidential Information, without violating the obligations of this Agreement, to the extent such disclosure is required by law or regulation or by a subpoena
      or other validly issued administrative or judicial process, provided that, Prospective Purchaser shall (a) provide Ionis with reasonable prompt notice of the disclosure(s) (to the extent legally permissible), (b) limit disclosure to only that portion
      of the Confidential Information which Prospective Purchaser is legally compelled to disclose and (c) reasonably cooperate in assisting Ionis (at Ionis&#8217; expense) in its efforts to ensure confidential treatment will be accorded any Confidential
      Information so furnished (to the extent legally permissible).</font></p>
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        or Destruction of Confidential Information</u>. Prospective Purchaser&#8217;s obligations to protect any Confidential Information received from the Ionis Parties shall continue for a period of three (3) years from the date of disclosure, notwithstanding
      whether or not Prospective Purchaser purchases the Property. At Ionis&#8217; written request, so long as the same is no longer necessary for Prospective Purchaser&#8217;s use in connection with the Purpose, Prospective Purchaser shall promptly destroy all
      copies, whether in written, electronic or other form or media, of the Ionis Parties&#8217; Confidential Information and certify in writing to Ionis that such Confidential Information has been destroyed; provided that Prospective Purchaser shall not be
      required to destroy electronic copies of any portions of the Confidential Information created pursuant to standard archival or back-up procedures and not available to end users, and provided that Prospective Purchaser may retain one (1) copy of the
      Confidential Information for its legal archives for the sole purpose of documenting its receipt thereof.</font></p>
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      Prospective Purchaser understands and agrees that Prospective Purchaser shall not obtain any proprietary interest in any Confidential Information. This Agreement shall not operate in a way to grant or confer any right or license in any of the
      Confidential Information, nor as a consent by the Ionis Parties to Prospective Purchaser for Prospective Purchaser&#8217;s use of any Confidential Information which may become public knowledge through any breach of this Agreement by or on behalf of
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      Confidential Information hereunder shall be construed as granting to Prospective Purchaser by implication, estoppel or otherwise, any right in or license under any present or future invention, trade secret, trademark, copyright, or patent, now or
      hereafter owned or controlled by the Ionis Parties.</font></p>
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      unauthorized disclosure or unauthorized use of the Confidential Information may irreparably injure the Ionis Parties. If any action should have to be brought by Ionis against Prospective Purchaser to enforce the provisions of this Agreement,
      Prospective Purchaser recognizes, acknowledges and agrees that Ionis shall be entitled to seek all of the civil remedies provided by federal, state and local law, including without limitation, preliminary and permanent injunctive relief restraining
      Prospective Purchaser from any actual or threatened unauthorized use or disclosure of any Confidential Information, in whole or in part. Nothing in this Agreement shall be construed as prohibiting Ionis from pursuing any other legal or equitable
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      (iii) sent by email, provided that the sender promptly delivers a hard copy to the recipient by the method set forth in (i) or (ii), in each case to the applicable addresses set forth below or to such other address as such Party has designated by
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          <p style="margin-top: 0; margin-bottom: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attention:</font></p>
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4401 Eastgate Mall</font></td>
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">San Diego, CA 92121-1909</font></td>
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      hereof. Following the acquisition of the Property by Prospective Purchaser or its Affiliate, if it occurs, this Agreement shall be deemed incorporated into the Lease by reference and shall terminate at such time, if any, as Prospective Purchase or
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        <td></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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      <tr style="vertical-align: top">
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      <tr style="vertical-align: top">
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      </tr>

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      </tr>

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      <tr style="vertical-align: top">
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      <tr style="vertical-align: top">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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  </table>
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      <tr style="vertical-align: top">
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.06</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.07</font></td>
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1.25in"></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
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      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">d)</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.08</font></td>
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      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0%"></td>
        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.01</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Inspection of Tenant Work in Progress</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0%"></td>
        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.02</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant is responsible for providing its contractor&#8217;s access to the
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: -0.1pt; margin-left: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0%"></td>
        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.03</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Public Safety</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: -0.05pt; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">It is the Tenants responsibility to ensure that the
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: -0.05pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
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        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.04</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: -0.05pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0%"></td>
        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>2.05</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
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      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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  </table>
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      <tr style="vertical-align: top">
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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  </table>
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  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  </table>
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      <tr style="vertical-align: top">
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  </table>
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      <tr style="vertical-align: top">
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  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Exhibit A</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      section.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      under $20,000,000; for work in excess of such amount, the limits of liability will be subject to Landlord&#8217;s reasonable approval. Landlord and Tenant shall reasonably cooperate in good faith to determine such insurance liability limits within thirty
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.</font></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Workers Compensation:</b> Statutory Coverage in accordance with the laws of your state.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.</font></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Employers Liability:</b> Limits of not less than $1,000,000 each accident/occurrence, <font style="font: 10pt Times New Roman, Times, Serif">$1,000,000 each employee/disease, $1,000,000 disease/policy limit.</font></font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font>&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.</font></td>
        <td style="text-align: justify; padding-right: 57.5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>General Liability:</b> Please see the chart below for General Liability per Occurrence/General Aggregate.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      limited to comprehensive form, premises operations, explosion and collapse hazard and underground hazard, products and a minimum of twelve (12) months completed operations hazard, contractual liability on a &#8220;blanket&#8221; basis designating all written
      contracts related to the work, broad form property damage (including completed operations), independent contractors&#8217; protective, personal injury liability, automobile liability comprehensive form for owned, hired and non-owned vehicles, elevators and
      escalators hazards, and incidental medical malpractice coverage hazards, and as follows: combined single limits for (i) bodily injury and (ii) property damages, endorsed such that the policy aggregate applies to each property location where work
      occurs. Bodily injury shall include, without limitation, damages for care and loss of services because of bodily injury, including death at any time resulting therefrom, sustained by any person or persons. Property Damage Liability Insurance shall
      include, without limitation, losses due to damages to or destruction of tangible property, including loss of use of such property resulting therefrom in compliance with the amounts set forth above; Contractor shall provide X, C and U coverage if
      Contractor&#8217;s operations involve any exposure to explosion, collapse or underground damage. Products and Completed Operations to be maintained for 3 years after final payment.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 32pt"></td>
        <td style="width: 27pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.</font></td>
        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Automobile Liability:</b> Bodily injury and property damage in an amount not less than $2,000,000 combined single limit covering all owned,
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      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.</font></td>
        <td style="text-align: justify; padding-right: 51.95pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Excess / Umbrella Liability:</b> $1,000,000 in excess of the above primary Employer&#8217;s Liability, General Liability,
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.</font></td>
        <td style="text-align: justify; padding-right: 35.85pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Property: </b>Property Insurance will cover the physical loss, including theft, or damage to equipment, machinery,
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 31.95pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.</font></td>
        <td style="text-align: justify; padding-right: 38.15pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Professional Liability (Errors and Omissions): </b>If the nature of the work involves a professional liability
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.</font></td>
        <td style="text-align: justify; padding-right: 30.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Contractors Pollution - Asbestos Legal Liability: </b>If the nature of the services performed involves pollutants
            or any other materials which would affect soil, water or structures, then the contractor shall maintain contractors pollution &#8211; asbestos legal liability coverage for a limit of not less than $1,000,000 each occurrence - $2,000,000 policy
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Certificate Holders, Additional Insured&#8217;s, and Additionally
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">CERTIFICATE OF INSURANCE LIMITS REQUIREMENT</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.</font></td>
        <td style="text-align: justify; padding-right: 47.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">For insurance requirements for crane lifts or any special contract work; contact for the property team for specific
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.</font></td>
        <td style="text-align: justify; padding-right: 76.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Commercial General Liability Coverage Required (millions, per occurrence and aggregate) is the sum of the basic
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">See Example for Electrical Maintenance below:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 18pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#9679;</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 18pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#9679;</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 32pt"></td>
        <td style="width: 18pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#9679;</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Certificate of Insurance Limits</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 40%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
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        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
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        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
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        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
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        <td style="width: 15%; border-top: black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Excess / Umbrella</b></font></p>
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        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Alarm Systems Service and Repair</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Appliance Repair &amp; Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Architectural <b>*</b></font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Asbestos Abatement and Hazardous Material Removal&#160;<b>****</b>&#160;</font></p>
        </td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Audio-Visual Equipment</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Backflow Testing</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM/1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Cabling</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Carpet/Floor Finishes</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Crane/Rigging</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Custom Fabrication &amp; Installation Millwork</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Doors &amp; Locks</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Electrical Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Elevator/Escalator Service &amp; Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Elevator interior installation</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Engineering Consulting Service<b>*</b></font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fire Extinguishing in Restaurants</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fitness Equipment Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Garbage Removal &amp; Disposal, incl. dumpster maintained
            on premises</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">General Contractors</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Generator Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Glass Repair &amp; Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Glass Repair &amp; Maintenance elevated</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; text-align: center; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; border-right: Black 1pt solid; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: center">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 40%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Type of Service&#160;</b></font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>General Liability</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Each Occurrence / General</b>&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Aggregate</b>&#160;</font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Employers&#8217; Liability&#160;</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Each Accident / Disease</b>&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>&#8211; Each Employee</b>&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>/ Disease &#8211; Policy</b>&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Limit</b>&#160;</font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Automobile Liability</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Combined Single Limit</b>&#160;</font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Excess / Umbrella</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Liability Each Occurrence / Aggregate</b>&#160;</font></p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Graffiti Removal</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Handyman</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Heating, Ventilation &amp; Air Conditioning
            Service/install</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Insulation/Fiberglass</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Interior Design Consulting<b>*</b></font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Life Safety/Fire Equipment</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Life Safety/Monitoring</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lighting re-lamping (interior)</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Elevated Lighting Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM /5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Moves/Relocations/reconfiguration</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Office Equipment Service</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Overhead and Revolving Door</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Painting</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Parking Surface Maintenance/sweeping</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Paving and Striping</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Plumbing</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Power washing (non-elevated)</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Power washing (elevated)</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM /5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pump Maintenance</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Roofing</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM /5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Signage non elevated</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Signage Elevated</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Sprinkler System Service and Repair</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Stonework/Marble/wood/metal cleaners and <font style="font: 10pt Times New Roman, Times, Serif">refinishers Repair &amp; Maintenance</font></font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; text-align: center; padding-right: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1MM</font></td>
        <td style="border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt; padding-right: 5.4pt; border-right: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2MM</font></td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: center">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 40%; border-top: black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Type of Service&#160;</b></font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>General Liability</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b>Each Occurrence / General&#160;</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Aggregate&#160;</b></font></p>
        </td>
        <td style="width: 15%; border-top: black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; padding-right: 5.4pt; padding-left: 5.4pt; text-align: center; vertical-align: bottom">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 14pt 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>TABLE OF CONTENTS</u></b></font>&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 14pt 0pt 0; text-align: right"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 14pt 0pt 0; text-align: center">&#160;</p>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom" colspan="2">&#160;</td>
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      </tr>
      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom" colspan="2">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article I</font></td>
        <td style="vertical-align: bottom" colspan="2"><font style="font: 10pt Times New Roman, Times, Serif">CERTAIN DEFINITIONS</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
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        <td style="vertical-align: top; width: 16%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom; width: 12%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 1.1</font></td>
        <td style="vertical-align: bottom; width: 67%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Definitions</font></td>
        <td style="vertical-align: bottom; width: 5%; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 1.2</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Rules of Construction</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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      <tr>
        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article II</font></td>
        <td style="vertical-align: bottom" colspan="2"><font style="font: 10pt Times New Roman, Times, Serif">PURCHASE AND SALE AGREEMENT; PURCHASE PRICE</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 2.1</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Purchase and Sale Agreement</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 2.2</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Purchase Price</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 2.3</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Deposit</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 2.4</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Independent Contract Consideration</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 2.5</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Indivisible Economic Package</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article III</font></td>
        <td style="vertical-align: bottom" colspan="2"><font style="font: 10pt Times New Roman, Times, Serif">DUE DILIGENCE ITEMS; FIRST RIGHT AGREEMENT</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 3.1</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Due Diligence Items</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Development Conditions</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">18</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 3.4</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">First Right Agreement</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">19</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article IV</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">20</font></td>
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        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 4.1</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Title to Real Property</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">20</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 4.2</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Objections and Certain Exceptions to Title</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 4.3</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 4.4</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Additional Title Matters</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">21</font></td>
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        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 4.5</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">21</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom; text-align: right">&#160;</td>
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        <td style="vertical-align: bottom" colspan="2"><font style="font: 10pt Times New Roman, Times, Serif">REMEDIES AND DEPOSIT INSTRUCTIONS</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">21</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 5.1</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Seller Default</font></td>
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        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 5.2</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">BUYER DEFAULT; LIQUIDATED DAMAGES</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
        <td style="vertical-align: bottom">&#160;</td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article VI</font></td>
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  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
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        <td style="vertical-align: bottom; width: 12%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom; width: 67%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom; text-align: center; width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Page</u></b></font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article VIII</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">31</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article IX</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">32</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: top"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td style="vertical-align: bottom; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">38</font></td>
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      <tr>
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      <tr>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 14pt 0pt 0; text-align: center"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 14pt 0pt 0; text-align: center"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">-ii-</font></div>
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        <td style="width: 84%; font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Description of Real Property</font></td>
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      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit B</b></font></td>
        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">List of Due Diligence Items</font></td>
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        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Disclosure Items</font></td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Form of First Right Agreement</font></p>
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        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit F</b></font></td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Form of Assignment and Assumption</font></p>
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        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit I</b></font></td>
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        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit J</b></font></td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Form of Owner&#8217;s Affidavit</font></p>
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        <td style="font-size: 10pt; padding-bottom: 8pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Exhibit M</b></font></td>
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      directly, or indirectly through one or more intermediaries, controls, is controlled by or is under common control with Buyer or Seller, as the case may be. For the purposes of this definition, &#8220;control&#8221; means the possession, direct or indirect, of
      the power to direct or cause the direction of the management and policies of a Person, whether through the ownership of voting securities, by contract or otherwise, and the terms &#8220;controlling&#8221; and &#8220;controlled&#8221; have the meanings correlative to the
      foregoing.</font></p>
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      2010 (U.K.), (iv) legislation adopted in furtherance of the OECD Convention on Combating Bribery of Foreign Public Officials in International Business Transactions, (v) the United States Bank Secrecy Act , as amended by the Anti Money Laundering Act
      of 2020; (vi) the Proceeds of Crime (Money Laundering) and Terrorist Financing Act (Canada), (vii) the Corruption of Foreign Public Officials Act (Canada), (viii) the U.K. Bribery Act, (ix) the Canadian Corruption of Foreign Public Officials Act, and
      (x) the Freezing Assets of Corrupt Foreign Public Officials Act (Canada), in each case as the same may be amended from time to time and including all rules, regulations, decrees, administrative orders, circulars, or instructions implementing or
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        Sanctions Laws</b>&#8221; means all anti-money laundering-related laws, regulations, and codes of practice applicable to Seller, its affiliates and their operations from time to time, including without limitation (i) the U.S. Money Laundering Control Act
      of 1986, (ii) the United States Bank Secrecy Act, as amended by the Anti Money Laundering Act of 2020, (iii) the United States International Money Laundering Abatement and Anti-Terrorist Financing Act of 2001, (iv) the United States Trading with the
      Enemy Act, and the regulations promulgated thereunder in 31 CFR Subtitle B, Chapter 5, as amended, (v) the International Emergency Economic Powers Act and the regulations promulgated thereunder in 31 CFR Subtitle B Chapter 5, as amended, (vi) the
      regulations of OFAC and The Financial Enforcement Network (FINCEN) or any enabling legislation or executive order relating thereto, (vii) the EU Anti-Money Laundering Directives, (viii) the Patriot Act and (ix) the applicable financial recordkeeping
      and reporting requirements of the U.S. Currency and Foreign Transaction Reporting Act of 1970, as amended, in each case as the same may be amended from time to time and including all rules, regulations, decrees, administrative orders, circulars, or
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      any Affiliates of Buyer, and their actual and potential investors, lenders, representatives, contractors (including, without limitation, any engineers, architects, bankers, contractors, and other professionals), employees and agents of Buyer or any
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      Lease Agreement between Buyer and Seller in the form attached hereto as <b><u>Exhibit M</u></b> and to be entered into and dated as of the Closing Date, whereby Seller shall lease all of the Property from Buyer.</font></p>
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      but is not limited to, the Comprehensive Environmental Response, Compensation and Liability Act of 1980, as amended (&#8220;<b>CERCLA</b>&#8221;), 42 U.S.C. &#167;9601 et seq.; the Toxic Substance Control Act, 15 U.S.C. &#167;2601 et seq.; the Hazardous Materials
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      the laws recited above, or otherwise relate to human health, natural resources or the environment, in each case together with their implementing regulations, guidelines, rules or orders, and all state, regional, county, municipal and other local
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      disclose, (b) all cash on hand or on deposit in any operating account or other account maintained in connection with the ownership, operation or management of the Real Property, (c) any licenses, permits and authorizations presently or hereafter
      issued to or for the benefit of Seller or its Affiliates in connection with Seller&#8217;s operation as a going concern and not otherwise necessary for the operation of the Real Property, (d) any intangible property whatsoever related to Seller or its
      Affiliates as a going concern, and (e) any Intellectual Property whatsoever owned or licensed by Seller or its Affiliates.</font></p>
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      lists maintained by the United States Department of Commerce (including the Denied Persons and Entities); (ii) the lists maintained by the United States Department of Treasury (OFAC) (Specially Designated National and Blocked Persons List, Sectoral
      Sanctions Identifications List and Foreign Sanctions Evaders List); (iii) the lists maintained by the United States Department of State (including the Terrorist Organizations, Munitions Control and Debarred Parties Lists); (iv) the Consolidated List
      of Financial Sanctions Targets and the Investment Ban List maintained by Her Majesty&#8217;s Treasury; and (v) all other lists of terrorists, terrorist organizations, cyber criminals, foreign persons interference in US elections, foreign corruption, human
      rights violators, proliferators of WMD, transnational criminal organizations or narcotics traffickers maintained pursuant to any of the rules and regulations of OFAC, the U.S. Department of the Treasury, by any other Governmental Authority or by any
      executive order (including Executive Order 13224 of September 24, 2001, as amended Executive Order Blocking Property and Prohibiting Transactions With Persons Who Commit, Threaten to Commit, or Support Terrorism) and any similar list maintained by,
      or public announcement of Sanctions designation made by, any of the Sanctions Authorities.&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Hazardous Materials</b>&#8221; means (a) any and all
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      pollutants&#8221;, &#8220;solid wastes,&#8221; or other similar designations in, or otherwise subject to regulation under the Environmental Laws, and (b) any other substances, constituents or wastes that are subject to Environmental Law, now or hereafter in effect,
      including but not limited to (A) petroleum, (B) refined petroleum products, (C) waste oil, (D) waste aviation or motor vehicle fuel and their byproducts, (E) asbestos, (F) lead in water, paint or elsewhere, (G) radon, (H) Polychlorinated Biphenyls
      (PCBs), (I) urea formaldehyde, (J) volatile organic compounds (VOC), (K) total petroleum hydrocarbons (TPH), (L) benzine derivative (BTEX), (M) poly- and perfluoroalkyl substances, and (N) petroleum byproducts.</font></p>
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      constitutes a trade secret, (b) any trademark and service mark rights, whether registered or not, applications to register and registrations of the same and like protections, and all goodwill connected with and symbolized by such trademarks, (c) all
      patents, patent applications and like protections including without limitation improvements, divisions, continuations, renewals, reissues, extensions and continuations-in-part of the same, (d) any and all trade secrets and trade secret rights,
      including, without limitation, any rights to unpatented inventions, know-how and operating manuals, (e) any and all source code, (f) any and all design rights which may be available to such Person, (g) any and all claims for damages by way of past,
      present and future infringement of any of the foregoing, with the right, but not the obligation, to sue for and collect such damages for said use or infringement of the Intellectual Property rights identified herein, and (h) all amendments, renewals
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      supplements thereto and guarantees thereof and all prepaid rent, tenant security deposits and other deposits, if any, thereunder; provided, however, the Leases shall not include the Buyer-Seller Lease.</font></p>
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      warrant, right of first refusal, easement, license, servitude, right of way, or zoning restriction.</font></p>
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      (Executive Order Blocking Property and Prohibiting Transactions with Persons Who Commit, Threaten to Commit, or Support Terrorism), any related enabling legislation or any other similar executive orders; (ii) the List of Specially Designated
      Nationals and Blocked Persons maintained by OFAC, and/or on any other similar list maintained by OFAC pursuant to any authorizing statute, executive order or regulation; or (iii) a &#8220;Designated National&#8221; as defined in the Cuban Assets Control
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      Discipline Over Monitoring Act (USA FREEDOM Act) of 2015 and as the same may be further amended, extended, replaced or otherwise modified from time to time, and any corresponding provisions of future laws.</font></p>
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      arising out of or in connection with the Real Property after the Closing Date (but excluding any claims or causes of action of Seller after the Closing arising from its rights under this Agreement or any documents to be delivered at the Closing), (c)
      the Licenses and Permits, (d) signage rights, utility and development rights and privileges, (e) site plans, surveys, environmental and other physical reports, plans and specifications pertaining to the foregoing, and (f) all licenses, covenants and
      other rights appurtenant to the Real Property, including, but not limited to, Seller&#8217;s right, title and interest in and to all development, density and similar rights, rights-of-way, open or proposed streets, alleys, easements, strips or gores of
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      United States Department of State, and Her Majesty&#8217;s Treasury; and (viii) all other similar governmental bodies with regulatory authority over Buyer or its affiliates issuing, administering, enacting or enforcing economic sanctions laws, regulations,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Substantial Damage</b>&#8221; shall have the meaning set forth in <u>Section</u>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Surviving Obligations</b>&#8221; shall mean any obligations of Buyer or
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Taking</b>&#8221; shall have the meaning set forth in <u>Section</u>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Tenant Improvements</b>&#8221; shall have the meaning ascribed to it in
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Title Company</b>&#8221; means First American Title National Commercial
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#8220;<b>Title Documents</b>&#8221; shall have the meaning set forth in Section 4.1.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Title Policy</b>&#8221; shall have the meaning set forth in Section 4.5.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#8220;<b>Transaction Costs</b>&#8221; shall have the meaning set forth in Section 5.1.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Unknown Environmental Condition</b>&#8221; means any
      Hazardous Materials at, on, under or migrating to or from, or having migrated to or from, the Property as of or prior to the Closing and not a Known Environmental Condition.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Unsafe Conditions</b>&#8221; shall have the meaning set forth in Section
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Work Letter&#8221; </b>shall mean that certain Work
      Letter attached as Exhibit D to the Buyer- Seller Lease. Notwithstanding that the Buyer-Seller Lease has not yet been executed, all of the terms and conditions of the Work Letter are incorporated herein by reference as of the Effective Date to the
      extent related to the Development Conditions and Seller&#8217;s obligation to achieve the same (such as Seller&#8217;s retention of the Architect), with references to &#8220;Landlord&#8221; meaning &#8220;Buyer&#8221; and &#8220;Tenant&#8221; meaning &#8220;Seller&#8221;.&#160;</font></p>
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  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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    shall not affect the construction of this Agreement. All references to &#8220;Article&#8221; or &#8220;Section&#8221; without reference to a document other than this Agreement, are intended to designate articles and sections of this Agreement, and the words &#8220;herein,&#8221;
    &#8220;hereof,&#8221; &#8220;hereunder,&#8221; and other words of similar import refer to this Agreement as a whole and not to any particular article or section, unless specifically designated otherwise. The use of the term &#8220;including&#8221; means in all cases &#8220;including but not
    limited to,&#8221; unless specifically designated otherwise. No rules of construction against the drafter of this Agreement shall apply in any interpretation or enforcement of this Agreement, any documents or certificates executed pursuant hereto, or any
    provisions of any of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE II&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>PURCHASE AND SALE AGREEMENT; PURCHASE PRICE</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.1 Purchase and Sale Agreement</b>. Seller agrees to sell, transfer, assign and convey to Buyer, and Buyer
    agrees to purchase, accept and assume, subject to the terms and conditions stated herein, all of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.2 Purchase Price</b>. Buyer shall pay Seller the purchase price (&#8220;<b>Purchase Price</b>&#8221;) in immediately
    available funds at Closing. The Purchase Price shall be equal to THIRTY-THREE MILLION AND NO/100 DOLLARS ($33,000,000.00). The Purchase Price, together with such other funds as may be necessary to pay Buyer&#8217;s required payments hereunder, subject to
    closing adjustments, shall be deposited with the Escrow Holder on or before 2:30 p.m. Pacific Time on the Closing Date in accordance with this Agreement. The Purchase Price shall be paid to Seller upon satisfaction of all conditions precedent to the
    Closing as described herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.3 Deposit</b>. Within three (3) Business Days of the Effective Date, Buyer shall deposit in escrow with Escrow
    Holder a deposit in the amount of TWO MILLION AND NO/100 DOLLARS ($2,000,000.00) (together with any interest earned thereon, the &#8220;<b>Deposit</b>&#8221;). All sums constituting the Deposit shall be held in an interest-bearing account as directed by Buyer, and
    interest accruing thereon shall be held for the account of the party entitled to the benefit of the Deposit pursuant to this Agreement. If the sale of the Property as contemplated hereunder is consummated, the Deposit shall be credited against the
    Purchase Price. Upon the Effective Date, the Deposit shall become non-refundable, except as otherwise expressly provided to the contrary herein. If Seller defaults under this Agreement or the sale of the Property is not consummated because of the
    failure of any condition precedent set forth in <u>Section 9.2(c)</u> or if this Agreement otherwise expressly provides for the return of the Deposit to the Buyer, then the Deposit plus interest accrued thereon shall immediately be returned to Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.4 Independent Contract Consideration</b>. Contemporaneously with the execution and delivery of this Agreement,
    Buyer shall deliver to Seller or Escrow Holder funds in the amount of One Hundred and No/100 Dollars ($100.00) (&#8220;<b>Independent Contract Consideration&#8221;</b>), which amount the parties bargained for and agreed to as consideration for Buyer&#8217;s right to
    inspect and purchase the Property pursuant to this Agreement, and for Seller&#8217;s execution, delivery, and performance of this Agreement. The Independent Contract Consideration is in addition to and independent of any other consideration or payment
    provided in this Agreement, is nonrefundable, and is fully earned and shall be retained by Seller notwithstanding any other provision of this Agreement.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">10</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 2.5 Indivisible Economic Package</b>. Buyer has no right to purchase, and Seller has no obligation to sell, less
    than all of the Property, it being the express agreement and understanding of Buyer and Seller that, as a material inducement to Seller and Buyer to enter into this Agreement, Buyer has agreed to purchase, and Seller has agreed to sell, all of the
    Property, subject to and in accordance with the terms and conditions hereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE III&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>DUE DILIGENCE ITEMS; FIRST RIGHT AGREEMENT</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 3.1&#160;&#160;&#160;&#160;&#160; Due Diligence Items<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>On or prior to the Effective Date, Seller has
    delivered to Buyer, or made available to Buyer for inspection via an online due diligence data room relating to the Property (the &#8220;<b>Data Room</b>&#8221;), the items described on attached <b><u>Exhibit B</u></b> (the &#8220;<b>Due Diligence Items</b>&#8221;);
    provided, however, that Seller was and is not obligated to deliver any Excluded Property to Buyer or make any Excluded Property available for its review. Buyer acknowledges that any and all documents actually in such Data Room have been made available
    to Buyer. In addition to such items in the Data Room, Seller shall make available to Buyer (by electronic means) any such other documents in Seller&#8217;s possession or control which relate to the Property, other than the Excluded Property, which Buyer
    shall reasonably request; provided, however, if Buyer requests information regarding the Excluded Property, then Seller shall, in good faith, consider whether it can make such information available to Buyer and make the same available to Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>All documents, materials, and information
    furnished to or made available to Buyer pursuant to this <u>Section</u> 3.1 are being furnished or made available to Buyer for information purposes only and without any representation or warranty by Seller with respect thereto, express or implied,
    except that, to Seller&#8217;s knowledge, they are in all material respects true, correct and complete originals or copies of the version of such materials Seller has in its files, and except as may otherwise be expressly set forth in Article VI and
    elsewhere in this Agreement and any other document delivered at Closing by Seller to Buyer, and as limited by <u>Section </u>6.2, and all such documents, materials, and information are expressly understood by Buyer to be subject to the
    confidentiality provisions of <u>Section</u> 3.2(d).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 3.2&#160;&#160;&#160;&#160;&#160;Due Diligence Inspection<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>During the period commencing on June 22, 2022
    and continuing thereafter until the Effective Date (the <b><i>&#8220;</i>Due Diligence Period</b>&#8221;), Buyer had the opportunity to analyze the feasibility of its ownership, operation, and use of the Property. Buyer acknowledges that Buyer is solely
    responsible for any and all costs incurred by Buyer in connection with its review and/or investigations of the matters set forth in this <u>Section 3.2</u>, including without limitation the costs of any studies and investigations performed by Buyer.&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">11</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; &#160;&#160; </font>Seller shall provide the Buyer Parties with
    reasonable access to the Property in accordance with the terms and conditions of this Agreement in order for Buyer to investigate the Property and the physical conditions thereof, including without limitation such non-invasive environmental,
    engineering, and economic feasibility inspections, and testing as Buyer may elect (the &#8220;<b>Due Diligence Activities</b>&#8221;). Such access, investigation, inspections, tests, and discussions shall be on the following terms and conditions:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in"> (i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Buyer shall pay for all inspections and tests ordered by Buyer.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>In connection with any entry
    by the Buyer Parties onto the Property, Buyer shall give Seller not less than forty-eight (48) hours&#8217; written notice (which notice may be given by e-mail) of the date and time of any desired Due Diligence Activity by a Buyer Party or as otherwise
    mutually agreed to by the parties. Any such entry on to the Property shall be conducted during Seller&#8217;s regular business hours; provided, however, that, in the event a Buyer Party requires access to the Property for conducting any Due Diligence
    Activities during hours outside Seller&#8217;s regular business hours (e.g., evenings or weekends), such access may be granted to Buyer Party, subject to Seller&#8217;s consent. Seller shall have the right to have a representative present during any visits to or
    inspections of the Property by a Buyer Party. Seller shall use reasonable efforts to make a representative available in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Buyer&#8217;s rights under this <u>Section</u>
    3.2, shall include the right to conduct non- invasive physical inspections of the Property, including, without limitation, surveys, physical assessments, so-called &#8220;Phase I&#8221; environmental site assessments, lead-based paint surveys, asbestos surveys or
    other non-invasive environmental inspections with respect to the Property, subject to the terms and conditions of this Agreement; provided, however, that such right shall in every instance be expressly subject to the condition that Buyer or its
    Affiliates shall be responsible for all payments or other financial obligations owed to the parties engaged by Buyer or its Affiliates to perform such non-invasive physical inspections. Notwithstanding anything in this Agreement to the contrary, any
    invasive physical inspections of the Property proposed to be conducted by Buyer, including without limitation so-called &#8220;Phase II&#8221; environmental site assessments or other environmental inspections or sampling with respect to the Property, shall require
    Seller&#8217;s prior written consent, which may be withheld in Seller&#8217;s sole and absolute discretion. In the event Buyer requests Seller&#8217;s consent to an invasive physical inspection of the Property (e.g., soil or groundwater sampling), Buyer shall submit to
    Seller such materials as shall fairly summarize, in reasonable detail, the scope of the work intended to be performed. Seller shall respond in writing to any Buyer request within five (5) days of receipt of any such request. Buyer or its Affiliates
    shall be responsible for all payments or other financial obligations owed to the parties engaged by Buyer to perform such invasive physical inspections of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iv)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Prior to and during any entry
    on the Property, Buyer shall secure and maintain at Buyer&#8217;s expense (or cause the relevant independent contractor hired by Buyer to enter on the Property to secure and maintain at that independent contractor&#8217;s expense) the following policies of
    insurance, which are to include coverage of Buyer, its agents&#8217;, employees&#8217; and contractors&#8217; activities at the Property: (a) comprehensive general liability insurance (including property damage, bodily injury, personal injury, and contractual liability
    coverage) in amounts of Two Million and 00/100 Dollars ($2,000,000.00) per occurrence and Two Million and 00/100 Dollars ($2,000,000.00) annual aggregate; and&#160; (b) comprehensive automobile liability insurance, with limits of One Million and 00/100
    Dollars ($1,000,000.00) combined single limit for each accident. The policies of insurance described in the preceding sentence shall name Seller as an additional insured. Buyer shall deliver certificates of insurance evidencing the insurance policies
    described in this (b)(iv) to Seller prior to the first entry on the Property by a Buyer Party. Any environmental contractor of Buyer which conducts environmental inspections of the Property shall, in addition to the insurance required of Buyer&#8217;s agents
    described above, also provide evidence of environmental liability insurance of not less than One Million and 00/100 Dollars ($1,000,000.00).&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">12</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(v)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Buyer shall promptly repair
    any damage to the Property caused by a Buyer Party&#8217;s entry or testing and shall, to the greatest extent feasible, restore the Property to its condition prior to such testing, at Buyer&#8217;s sole cost and expense; provided, however, that Buyer will have no
    obligation to restore any damage to the extent caused by Seller&#8217;s negligence or misconduct (as well as that caused by any of Seller&#8217;s agents, employees, contractors, shareholders, partners, members, officers and directors) or to repair, remediate or
    restore any existing defects or conditions discovered by Buyer or a Buyer Party. Until restoration is complete, Buyer will take commercially reasonable steps to cause any conditions on the Property created by Buyer&#8217;s or Buyer Party&#8217;s testing to not
    interfere with the normal operation of the Property or create any dangerous conditions on the Property. Buyer shall not commit or suffer to be committed, any waste upon the Property. No Buyer Party may construct, erect or place on the Property any
    monuments or permanent improvements.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(vi)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>Buyer shall conduct the Due
    Diligence Activities in accordance with all applicable laws and, if required by applicable laws, under the supervision of Governmental Entities having jurisdiction over the Due Diligence Activities.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(vii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;</font>Buyer agrees to keep and
    maintain the Property free and clear of all labor liens, mechanics and materialmen liens, or other clouds, encumbrances and charges occurring as a result of any act done, suffered, or committed or indebtedness incurred by a Buyer Party in connection
    with any Due Diligence Activities.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(viii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;</font>Buyer hereby indemnifies,
    protects, defends and holds harmless Seller, its Affiliates, their directors, officers, employees, agents, successors and assigns (collectively, the &#8220;<b>Seller Indemnified Parties</b>&#8221;, and each a &#8220;<b>Seller Indemnified Party</b>&#8221;) from and against any
    and all actual, out of pocket Claims that any Seller Indemnified Party suffers or incurs as a result of a Buyer Party&#8217;s entry or conduct upon the Property or performance of any Due Diligence Activity pursuant to this Agreement; provided, however, that
    the foregoing indemnity shall not extend to protect the Seller Indemnified Parties from any pre-existing liabilities for matters merely discovered or observed by a Buyer Party, including, without limitation, any physical conditions at the Property or
    any existing environmental contamination, a Known Environmental Condition, or an Unknown Environmental Condition, or any Claims due to or arising from acts or omissions attributable to Seller, except to the extent exacerbated by Buyer.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">13</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ix)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller is not an insurer of
    Buyer&#8217;s person or property. To the maximum extent allowed by applicable laws, Seller shall not be liable to Buyer for any bodily injury or property damage suffered by any Buyer Party as a result of a Buyer Party&#8217;s entry or conduct upon the Property or
    performance of any Due Diligence Activity pursuant to this Agreement, except to the extent arising from Seller&#8217;s gross negligence or willful misconduct. Buyer acknowledges and agrees that Buyer, by electing to exercise its rights of access hereunder,
    shall be deemed to have assumed all risk of loss of personal injury or property damage to any Buyer Party as a result of a Buyer Party&#8217;s entry or conduct upon the Property or performance of any Due Diligence Activity pursuant to this Agreement, except
    to the extent arising from Seller&#8217;s negligence or willful misconduct.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">The provisions of this (b) shall survive the termination of this Agreement and delivery of the Deed for a period of nine (9) months.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Waiver of Termination</u>. By execution of
    this Agreement, Buyer has waived its right to deliver written notice of its disapproval of the Property, except as expressly set forth in this Agreement. As a result thereof, the Deposit is non-refundable except as otherwise expressly stated herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Confidentiality</u>. Until the Closing,
    except as permitted hereunder, Buyer and Seller shall each (and Buyer shall cause the Buyer Parties to) maintain in confidence all non-public information concerning the Property which Seller or its representatives have disclosed or delivered, or shall
    hereafter disclose or deliver to Buyer and/or the Buyer Parties, including, but not limited to, (i) any Due Diligence Items and information provided by Seller to Buyer or the Buyer Parties in the conduct of its Due Diligence or that was posted to the
    diligence website, and (ii) the results of any inspections of the Property conducted by Buyer pursuant to this Agreement (collectively, the &#8220;<b>Confidential Information</b>&#8221;), and, shall not, without Seller&#8217;s prior written consent, which may be
    withheld in Seller&#8217;s sole and absolute discretion, deliver or disclose the same, or any part thereof, to any other Person or entity except as may be required by applicable law, regulation or legal process; provided, however, Buyer and Seller may
    disclose any such confidential information to its agents, attorneys, advisors, consultants, prospective lenders or investors, and employees involved in the review and inspection of the Property or as may be required by law or by any court or
    administrative order. For the avoidance of doubt, &#8220;Confidential Information&#8221; shall not include: (i) information already in Buyer&#8217;s or any Buyer Parties&#8217; possession prior to its receipt thereof from Seller or its representative; (ii) information which
    is obtained by Buyer or any Buyer Parties from a third person who is not prohibited from disclosing such information to it by any contractual, legal or fiduciary obligation to Seller; (iii) information which is or becomes publicly disclosed through no
    fault of the Buyer or any Buyer Parties; or (iv) information which is required to be disclosed by a court of competent jurisdiction in connection with any litigation between the parties hereto. Notwithstanding the foregoing, Buyer may disclose and
    deliver Confidential Information to the Buyer Parties on a need to know basis. Buyer shall not use nor permit the Buyer Parties to use any of the Confidential Information for any purpose other than the evaluation of the Property and the transaction
    described herein. Notwithstanding anything to the contrary in this Agreement, neither Seller nor Buyer shall release or permit to be released any press release or other similar communication relating to the transaction contemplated by this Agreement
    before Closing without the prior written consent of the other party. Nothing in this <u>Section </u>3.2(d) shall be deemed to void, supersede, or modify any other confidentiality, nondisclosure or similar agreements entered into between Buyer and
    Seller prior to the Effective Date hereof. The provisions of this <u>Section</u> 3.2(d) shall survive the Closing or any termination of this Agreement.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">14</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;</font><u>AS-IS</u>. Buyer hereby acknowledges that
    except as is otherwise expressly provided in this Agreement and subject to Seller&#8217;s representations and warranties expressly set forth herein, or in any other documents delivered to Buyer upon the Closing (each such document, a &#8220;<b>Closing Document</b>&#8221;),






    it is relying upon its own inspections, investigations and analyses of the Property in entering into this Agreement and, except as otherwise provided in this Agreement or in any Closing Document, and subject to Seller&#8217;s covenants, representations and
    warranties expressly set forth herein and in any Closing Document, is not relying in any way upon any representations, statements, agreements, warranties, studies, reports, descriptions, guidelines or other information or material furnished by Seller
    or its representatives, whether oral or written, express or implied, of any nature whatsoever regarding any such matters, including, without limitation, as to the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The condition, value,
    nature, or quality of the Property, including any construction on the Property and any materials or systems incorporated into the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in"> (ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160; The soil, water or geology relating to the Property.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in"> (iii)&#160;&#160;&#160;&#160;&#160;&#160; Any income to be derived from the Property.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iv)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>The suitability of the
    Property for any activities or uses which Buyer may wish to conduct on or relating to the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in"> (v)&#160;&#160;&#160;&#160;&#160;&#160;&#160;The zoning or developability of the Property.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(vi)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>Compliance of the Property or
    its operation with any law, ordinance, rule, regulation, or the status of any permits or approvals relating to or required in connection with the Property, including without limitation the Americans with Disabilities Act, 42 U.S.C. &#167;12101 et seq. (or
    any successor statute or similar state and local laws).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(vii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;</font>The presence or absence of any
    Hazardous Materials on or about the Property or in the vicinity of the Property or the compliance of the Property with Environmental Laws; and Buyer expressly acknowledges that the Property Documents constitute written notice to Buyer as may be
    required by California Health and Safety Code <u>Section </u>25359.7.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">15</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Buyer specifically acknowledges and agrees that, to the extent Seller has made or in the future makes any information (including without
    limitation the Due Diligence Items) regarding any aspect of the Property available to Buyer, Seller has done or will be doing so only as an accommodation to Buyer and that, except as expressly provided elsewhere in this Agreement and in any Closing
    Document, and subject to Seller&#8217;s express covenants, representations and warranties in this Agreement and the Closing Documents, Seller has not made, is not making, and shall make no representation or warranty of any nature concerning the accuracy or
    completeness of Seller&#8217;s files or concerning the authenticity, source, accuracy or completeness of any information contained in them or furnished or to be furnished by Seller to Buyer (including without limitation the Due Diligence Items). As to
    certain of the materials furnished to Buyer from Seller&#8217;s files, Buyer specifically acknowledges that they have been prepared by third parties with whom Seller has no privity and Buyer acknowledges and agrees that no warranty or representation, express
    or implied, has been made, nor shall any be deemed to have been made, to Buyer either by Seller or by any third parties that prepared the materials in question, except as otherwise provided in this Agreement and in any Closing Document and subject to
    Seller&#8217;s express representations and warranties in this Agreement and the Closing Documents. Except as otherwise provided in this Agreement, in any Closing Document and subject to the Excluded Claims, Buyer waives any claim of any nature against Seller
    if any information, conclusion, projection, or other statement of any nature contained in any of those materials should prove not to be true, complete, or accurate for any reason. By its execution of this Agreement, Buyer acknowledges and agrees that a
    material inducement to Seller&#8217;s decision to sell the Property to Buyer at the Purchase Price provided in this Agreement was Buyer&#8217;s agreement to conduct its own feasibility studies and purchase the Property in an &#8220;AS-IS&#8221; condition, subject to the
    express covenants, representations and warranties of Seller set forth in this Agreement or in any Closing Document. Subject to the express covenants, representations and warranties of Seller set forth in this Agreement or in any Closing Document, Buyer
    has completed all of its diligence during the Due Diligence Period and Buyer acknowledges and agrees that it shall accept the Property in its condition as of the Closing.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">16</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>No Liability
        for Information</u>. BUYER REPRESENTS THAT IT IS A KNOWLEDGEABLE, EXPERIENCED AND SOPHISTICATED BUYER OF REAL ESTATE, AND THAT IT IS RELYING SOLELY ON THE EXPRESS REPRESENTATIONS AND WARRANTIES OF SELLER MADE IN THIS AGREEMENT AND ANY OTHER CLOSING
      DOCUMENT, ITS OWN EXPERTISE, AND THAT OF BUYER&#8217;S CONSULTANTS IN PURCHASING THE PROPERTY. ANY INFORMATION PROVIDED OR TO BE PROVIDED WITH RESPECT TO THE PROPERTY IS SOLELY FOR BUYER&#8217;S CONVENIENCE AND WAS OR WILL BE OBTAINED FROM A VARIETY OF SOURCES.
      SELLER HAS NOT MADE ANY INDEPENDENT INVESTIGATION OR VERIFICATION OF SUCH INFORMATION AND MAKES NO (AND EXPRESSLY DISCLAIMS ALL) REPRESENTATIONS AS TO THE ACCURACY OR COMPLETENESS OF SUCH INFORMATION (EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS
      AGREEMENT AND THE CLOSING DOCUMENTS). EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS AGREEMENT AND THE CLOSING DOCUMENTS AND THE EXCLUDED CLAIMS, SELLER SHALL NOT BE LIABLE FOR ANY MISTAKES, OMISSIONS, MISREPRESENTATION OR ANY FAILURE TO
      INVESTIGATE THE PROPERTY NOR SHALL SELLER BE BOUND IN ANY MANNER BY ANY VERBAL OR WRITTEN STATEMENTS, REPRESENTATIONS, APPRAISALS, ENVIRONMENTAL ASSESSMENT REPORTS, OR OTHER INFORMATION PERTAINING TO THE PROPERTY OR THE OPERATION THEREOF, FURNISHED
      BY (A) SELLER, (B) ANY PARTNERSHIP, LIMITED LIABILITY COMPANY, CORPORATION, TRUST OR OTHER ENTITY THAT HAS OR ACQUIRES A DIRECT OR INDIRECT INTEREST IN SELLER, (C) ANY DIRECT OR INDIRECT MEMBER, MANAGER, MANAGING MEMBER, PARTNER, ADVISOR, TRUSTEE,
      BENEFICIARY, DIRECTOR, OFFICER, SHAREHOLDER, EMPLOYEE, PARTICIPANT, REPRESENTATIVE OR AGENT IN OR OF SELLER OR OF ANY ENTITY </font>THAT HAS OR ACQUIRES A DIRECT OR INDIRECT INTEREST IN SELLER, OR (D) ANY REAL ESTATE BROKER, AGENT, OR OTHER PERSON
    OR ENTITY ACTING ON SELLER&#8217;S BEHALF. EXCEPT TO THE EXTENT EXPRESSLY SET FORTH IN THIS AGREEMENT AND THE CLOSING DOCUMENTS, BUYER WILL ACQUIRE THE PROPERTY SOLELY ON THE BASIS OF ITS OWN PHYSICAL AND FINANCIAL EXAMINATIONS, REVIEWS AND INSPECTIONS AND
    THE TITLE INSURANCE PROTECTION AFFORDED BY THE TITLE POLICY. EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT OR THE CLOSING DOCUMENTS (INCLUDING, WITHOUT LIMITATION, SELLER&#8217;S REPRESENTATIONS AND WARRANTIES HEREIN AND THEREIN), SELLER SPECIFICALLY
    DISCLAIMS, AND NEITHER IT NOR ANY OTHER PERSON IS MAKING, ANY REPRESENTATION, WARRANTY OR ASSURANCE WHATSOEVER TO BUYER AND NO WARRANTIES OR REPRESENTATIONS OF ANY KIND OR CHARACTER, EITHER EXPRESS OR IMPLIED, ARE MADE BY SELLER OR RELIED UPON BY BUYER
    WITH RESPECT TO THE STATUS OF TITLE TO OR THE MAINTENANCE, REPAIR, CONDITION, DESIGN OR MARKETABILITY OF THE PROPERTY, OR ANY PORTION THEREOF, INCLUDING BUT NOT LIMITED TO (I) ANY IMPLIED OR EXPRESS WARRANTY OF MERCHANTABILITY, (II) ANY IMPLIED OR
    EXPRESS WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE, (III) ANY IMPLIED OR EXPRESS WARRANTY OF CONFORMITY TO MODELS OR SAMPLES OF MATERIALS, (IV) ANY RIGHTS OF BUYER UNDER APPROPRIATE STATUTES TO CLAIM DIMINUTION OF CONSIDERATION, (V) ANY CLAIM BY
    BUYER FOR DAMAGES BECAUSE OF DEFECTS, WHETHER KNOWN OR UNKNOWN, WITH RESPECT TO THE IMPROVEMENTS OR THE PERSONAL PROPERTY, AND (VI) THE FINANCIAL CONDITION OR PROSPECTS OF THE PROPERTY, IT BEING THE EXPRESS INTENTION OF SELLER AND BUYER THAT, EXCEPT AS
    EXPRESSLY SET FORTH IN THIS AGREEMENT, THE PROPERTY WILL BE CONVEYED AND TRANSFERRED TO BUYER IN ITS PRESENT CONDITION AND STATE OF REPAIR, &#8220;AS IS&#8221; AND &#8220;WHERE IS&#8221;, WITH ALL FAULTS. BUYER, WITH BUYER&#8217;S COUNSEL, HAS FULLY REVIEWED THE DISCLAIMERS,
    RELEASES AND WAIVERS SET FORTH IN THIS AGREEMENT, AND UNDERSTANDS THE SIGNIFICANCE AND EFFECT THEREOF. BUYER ACKNOWLEDGES AND AGREES THAT THE DISCLAIMERS, RELEASES, WAIVERS AND OTHER AGREEMENTS SET FORTH HEREIN ARE AN INTEGRAL PART OF THIS AGREEMENT,
    AND THAT SELLER WOULD NOT HAVE AGREED TO SELL THE PROPERTY TO BUYER FOR THE PURCHASE PRICE WITHOUT THE DISCLAIMERS, RELEASES, WAIVERS AND OTHER AGREEMENTS SET FORTH IN THIS AGREEMENT.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Release by Buyer</u>. Notwithstanding any
    other provisions contained herein, or in any Closing Document, to the contrary (including, without limitation, any language providing for survival of certain provisions hereof or thereof), Buyer hereby acknowledges and agrees that (a) prior to Closing,
    Buyer&#8217;s sole recourse in the event of a breach by Seller under this Agreement only shall be as set forth in <u>Section 5.1</u> hereof, and (b) Seller shall, upon consummation of Closing, be deemed to have satisfied and fulfilled all of Seller&#8217;s
    covenants, indemnities, and obligations contained in this Agreement which do not expressly survive Closing and the documents delivered pursuant hereto, and Seller shall have no further liability to Buyer or otherwise with respect to this Agreement, the
    Property, the transfers contemplated hereby, or any documents delivered pursuant hereto, except to the extent of any obligation or liability Seller may expressly have under this Agreement, the Closing Documents or with respect to any Excluded Claim.
    Except for the Excluded Claims or as otherwise provided in this Agreement or any of the Closing Documents, Buyer hereby waives its right to recover from, and fully and irrevocably releases Seller and its Indemnified Parties from any and all Claims
    other than the Excluded Claims that it may now have or hereafter acquire against any Seller or any of the Indemnified Parties arising from or related to any defects, errors, omissions or other conditions, latent or otherwise, affecting the Property.
    With respect to the release set forth in this <u>Section 3.2</u>, Buyer specifically waives the provision of California Civil Code Section 1542. Section 1542 provides as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 1in; text-align: justify">&#8220;A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS WHICH THE CREDITOR OR RELEASING PARTY DOES NOT KNOW OR EXPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE
    RELEASE, WHICH IF KNOWN TO HIM OR HER WOULD HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.&#8221;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt">BUYER&#8217;S INITIALS: &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;/s/<u> &#160;KB&#160;&#160;&#160;&#160;&#160;</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(h)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Excluded Claims</u>. Notwithstanding anything
    to the contrary contained in this <u>Section 3.2</u> or elsewhere in this Agreement, the parties acknowledge and agree that the waivers and releases by Buyer set forth in this <u>Section 3.2</u> or elsewhere in this Agreement or any Closing Document
    shall not apply to, limit or affect, and the released Claims shall expressly not include, any Claims resulting or arising from any of the following (each, an &#8220;<b>Excluded Claim</b>&#8221;) (i) a breach of any representation or warranty of Seller set forth in
    this Agreement or any of the Closing Documents, (ii) Seller&#8217;s fraud or intentional misrepresentation, (iii) third party tort claims arising prior to the Closing Date, (iv) the Surviving Obligations of Seller including all of Seller&#8217;s indemnity
    obligations set forth in this Agreement, or (v) obligations or matters under the Buyer- Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Survival</u>. The provisions of <u>Sections
      3.2(f)</u>-<u>(i)</u> shall survive the Closing or any earlier termination of this Agreement and delivery of the Deed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 3.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Development Conditions</u><font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Buyer shall not be obligated to close this
    transaction unless (a) Seller shall have obtained the Entitlements required in connection with the development of the Property as contemplated by the Work Letter and, which at a minimum, satisfy the Fundamental Requirements and other requirements set
    forth in the Work Letter, with all appeals periods having expired without any appeal having been filed (or any appeal therefrom having been dismissed with prejudice and not subject to further appeal) (the &#8220;<b>Permits and Approvals Condition</b>&#8221;) and
    (b) otherwise completed the schematic design documents for the Landlord&#8217;s Construction Work and advanced the design of the Tenant Improvements to the point contemplated by the Work Letter as of the effective date of the Buyer-Seller Lease (the &#8220;<b>Shell






      and Core Design Condition</b>&#8221;; collectively with the Permits and Approvals Condition, the &#8220;<b>Development Conditions</b>&#8221;). The Permits and Approvals and schematic design documents for Landlord&#8217;s Construction Work shall be subject to the final
    written approval of Buyer as further set forth in the Work Letter, as incorporated herein.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller shall diligently and continuously pursue
    the Entitlements as required by the Work Letter, including by appearing at public hearings, city staff meetings, and other meetings related to the Entitlements and taking all other actions necessary and appropriate to obtain the Entitlements and cause
    the Permits and Approvals Condition to be satisfied on or before the Outside Satisfaction Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>If the Permits and Approvals Condition has not
    been satisfied by February 1, 2023 (the &#8220;<b>Step-In Outside Date</b>&#8221;), Buyer shall have the right (but not the obligation) (the &#8220;<b>Step-In Right</b>&#8221;) upon five (5) Business Days&#8217; written notice to Seller at any time thereafter during the term of
    this Agreement to take over the process to obtain the Entitlements, at Seller&#8217;s sole cost and expense (but such costs and expenses shall be treated as Construction Costs under the Work Letter). Seller shall reasonably cooperate with Buyer in connection
    with Buyer&#8217;s exercise of the Step-In Right in all respects and take all commercially reasonable actions necessary and appropriate in connection therewith, including, without limitation, attending any meetings related to obtaining the Entitlements,
    executing any documents, instruments or agreements related to the Entitlements, and effectuating the assignment or transfer of any permits, licenses, or approvals (to the extent assignable) if requested by Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Further, if the Development Conditions have not
    been satisfied by April 1, 2023 (as it may be extended pursuant to this <u>Section 3.3(d)</u>, the &#8220;<b>Outside Satisfaction Date</b>&#8221;) or Buyer determines at any time before the Outside Satisfaction Date that Seller has been or will be unable to
    satisfy the Development Conditions, then Buyer may, by delivering written notice to Seller, (i) terminate this Agreement; (ii) waive such condition and proceed with the Closing on a date designed by Buyer not later than [thirty (30)] days after the
    Outside Satisfaction Date; or (iii) extend the Outside Satisfaction Date one (1) or more times to provide additional time for the Development Conditions to be satisfied, such extension not to exceed one hundred twenty (120) days in the aggregate. In
    the event Buyer desires to exercise such extension right, Buyer shall give written notice to Seller and Escrow Holder on or before five (5) Business Days prior to the then-applicable Outside Satisfaction Date. If Buyer terminates this Agreement in
    accordance with this <u>Section </u>3.3(d), Escrow Holder shall promptly return the Deposit to Buyer and neither Party shall have any further rights or obligations hereunder, except for the Surviving Obligations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 3.4&#160;&#160;&#160;&#160;&#160;&#160; <u>First Right Agreement</u></b>. If the sale of the Property is not consummated on the Closing Date
    for any reason other than a default by Buyer, then Buyer shall have a right of first offer and right of first refusal to purchase or otherwise acquire Seller&#8217;s interest in the Property, subject to and in accordance with the terms and conditions of the
    First Right Agreement. Concurrently with the execution and delivery of this Agreement, the parties shall each deliver to Escrow Holder an executed and acknowledged counterpart to the First Right Agreement as well as a memorandum of the First Right
    Agreement in the form of <u>Exhibit G-2</u> attached hereto (the &#8220;<b>First Right Memo</b>&#8221;). Escrow Holder is hereby instructed to record the First Right Memo in the Official Records of San Diego County in the event the sale of the Property is not
    consummated on the Closing Date for any reason other than a default by Buyer.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in"></p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE IV <br>
    TITLE AND SURVEY</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.1&#160;&#160;&#160;&#160;&#160; Title to Real Property</b>. Buyer may obtain (a) a commitment to issue an owner&#8217;s policy of title
    insurance with respect to the Property issued by the Title Company in favor of Buyer (the &#8220;<b>Title Commitment</b>&#8221;), and (b) copies of all documents referred to on Schedule B of the Title Commitment as exceptions to coverage (the &#8220;<b>Title Documents</b>&#8221;).







    Buyer hereby acknowledges that it has received a preliminary title report (&#8220;<b>Preliminary Report</b>&#8221;) attached hereto as <b>Exhibit D</b>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.2&#160;&#160;&#160;&#160;&#160; Objections and Certain Exceptions to Title</b>. Prior to the Effective Date, Buyer delivered to Seller a
    notice (the &#8220;<b>Title Objection Notice</b>&#8221;) of any matters affecting title to the Real Property contained in the Preliminary Report, or any matters reflected on a survey obtained by Buyer, to which Buyer objects (the &#8220;<b>Title Objections</b>&#8221;). Seller
    has agreed to use commercially reasonable efforts to obtain an estoppel certificate from Techbuilt Construction Corp or its successor in interest as declarant in the form previously provided by Buyer to Seller or Seller&#8217;s counsel with respect to that
    certain Declaration of Covenants, Conditions and Restrictions for Carlsbad Oaks North Business Park recorded on February 5, 2007 as Instrument Number 2007- 0081082 with the Official Records of the San Diego County Recorder&#8217;s Office. Notwithstanding
    anything to the contrary in this Agreement, Seller will be obligated to remove or cure on or before the Closing (whether or not Buyer has objected thereto in writing), in each case, exceptions to title to the Property which are (a) any mortgage liens
    or other monetary liens affecting the Property (except to the extent created by or arising from the acts or omissions of a Buyer Party), (b) mechanics&#8217; liens, materialmen&#8217;s liens and claims of liens for labor materials furnished or supplied to the
    Property or any portion thereof by or on behalf of Seller or its property manager (if applicable), affecting the Property (except to the extent created by or arising from the intentional acts or omissions of a Buyer Party), (c) code violations and
    other violations with respect to the Property that can be satisfied by payment of a liquidated amount or bonding, (d) encumbrances that have been placed against the Property by, through or under Seller after the date of this Agreement without Buyer&#8217;s
    prior written consent, (e) so called &#8220;standard&#8221; exceptions that can be removed from the Title Policy by Seller&#8217;s delivery of the Owner&#8217;s Affidavit, (f) tax liens for real property taxes and assessments which are due and payable or any judgment liens,
    and (g) any other voluntary or involuntary liens or utility liens created or suffered by Seller (not otherwise covered by clauses (a)-(f)) capable of being cleared from title by the payment of a sum certain (the liens described in clauses (a) through
    (g) are collectively referred to as, &#8220;<b>Seller&#8217;s Required Removal Items</b>&#8221;). If Seller fails to remove Seller&#8217;s Required Removal Items at or prior to Closing, such failure shall constitute a Seller default and the terms of <u>Section 5.1</u> herein
    shall apply. Except with respect to Seller&#8217;s Required Removal Items and the other matters expressly set forth in this <u>Section 4.2</u>, Seller shall have no obligation whatsoever to expend or agree to expend any funds, to undertake or agree to
    undertake any obligations or otherwise to cure or agree to cure any title objections.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.3&#160;&#160;&#160;&#160;&#160;&#160; Natural Hazard Expert</b>. Buyer and Seller acknowledge that Seller is required to disclose if any
    portion of the Property lies within a natural hazard area or zone. Buyer and Seller agree that Seller may employ the services of Escrow Holder, a company recommended by Escrow Holder, or an affiliate of Escrow Holder (as so employed, the &#8220;<b>Natural
      Hazard Expert</b>&#8221;) to examine the maps and other information specifically made available to the public by government agencies for the purposes of enabling Seller to fulfill its disclosure obligations with respect to the natural hazards referred to
    above and to report the results of its examination to Buyer and Seller in writing. No later than five (5) days after the Effective Date, Seller, at its sole cost and expense, shall provide Buyer with a Natural Hazard Disclosure Statement prepared by a
    Natural Hazard Expert.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.4&#160;&#160;&#160;&#160;&#160;&#160; Additional Title Matters</b>. If the Title Company revises the Title Commitment after the Effective
    Date to add or modify exceptions (other than new or modified exceptions that do not have a material adverse effect on the value, use and/or functionality of the Property) or if a Survey is modified as a result thereof in an adverse manner to Buyer,
    then Buyer shall have two (2) Business Days after Buyer obtains knowledge of such addition or modification to notify Seller that such additions or modifications are not acceptable to Buyer (in Buyer&#8217;s sole and absolute discretion) (a &#8220;<b>Title Notice</b>&#8221;).






    If Buyer fails to deliver a Title Notice as aforesaid, then such addition or modification shall be deemed a Permitted Exception. To the extent Buyer timely delivers a Title Notice, then Seller shall deliver, within two (2) Business Days of its receipt
    of such Title Notice, written notice to Buyer and Title Company identifying which disapproved items (other than Seller&#8217;s Required Removal Items, which Seller is obligated to cure regardless of such notification) Seller shall undertake to cure or not
    cure (&#8220;<b>Seller&#8217;s Response</b>&#8221;). If Seller does not timely deliver a Seller&#8217;s Response, Seller shall be deemed to have elected to not remove or otherwise cure any exceptions disapproved by Buyer. If Seller elects, or is deemed to have elected, not to
    remove or otherwise cure an exception disapproved in the Title Notice, Buyer may terminate this Agreement upon written notice to Seller within the sooner of two (2) Business Days after receipt or deemed receipt of the Title Notice, and the Closing
    Date. If Seller elects, in Seller&#8217;s Response, to cure an exception disapproved in the Title Notice, and Seller fails to cure such matter at or prior to Closing, Buyer may terminate this Agreement. The term &#8220;<b>Permitted Exceptions</b>&#8221; will mean, (i)
    Title Objections which Seller did not elect to cure pursuant to <u>Section 4.2</u> above, (ii) real estate taxes not yet due and payable but otherwise subject to proration as provided in this Agreement, and (iii) any exceptions caused by Buyer, its
    agents, representatives, or employees. Notwithstanding anything to the contrary set forth herein, Seller will have the obligation to cure and cause to be released of record concurrent with, or prior to, the Closing, the Seller&#8217;s Required Removal Items.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 4.5&#160;&#160;&#160;&#160;&#160;&#160;Title Insurance</b>. At Closing, and as a condition thereto for Buyer&#8217;s benefit, the Title Company shall
    issue to Buyer or be irrevocably committed to issue to Buyer a standard coverage ALTA owner&#8217;s form title policy in the form of the Pro Forma (the &#8220;<b>Title Policy</b>&#8221;), in the amount of the Purchase Price, insuring that fee simple title to the Real
    Property is vested in Buyer subject only to the Permitted Exceptions.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE V&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>REMEDIES AND DEPOSIT INSTRUCTIONS</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 5.1&#160;&#160;&#160;&#160;&#160;&#160; Seller Default</b>. If the sale of the Property is not consummated due to the permitted termination of
    this Agreement by Buyer as expressly provided in this <u>Section</u> 5.1 or due to the failure of a condition precedent set forth in <u>Section</u> 9.2(c), the Deposit shall be returned to Buyer, Seller shall reimburse Buyer for Buyer&#8217;s actual
    reasonable out-of-pocket, third party costs and fees (including attorneys&#8217; fees) incurred by Buyer in connection with the transaction contemplated by this Agreement (including, but not, limited to such costs associated with due diligence investigation
    of the Property, negotiation of this Agreement and/or efforts to finance the acquisition of the Property) not to exceed a total aggregate amount of TWO HUNDRED FIFTY THOUSAND AND 00/DOLLARS ($250,000.00) (the &#8220;<b>Transaction Costs</b>&#8221;) and Buyer will
    have no liability hereunder except for the Surviving Obligations. If the sale of the Property is not consummated due to a breach or default by Seller in the performance of any of its obligations under this Agreement, then Buyer shall be entitled, as
    its sole and exclusive remedy, either: (a) to terminate this Agreement and receive the return of the Deposit, together with a reimbursement to Buyer for its Transaction Costs, whereupon the parties shall be released from all further obligations under
    this Agreement, except the Surviving Obligations; or (b) to enforce specific performance of the sale of the Property pursuant to this Agreement. Buyer shall be deemed to have elected to terminate this Agreement and receive back the Deposit and a
    reimbursement of the Transaction Costs as set forth hereinabove if Buyer fails to file suit for specific performance against Seller in a court prescribed by <u>Section 11.4</u> hereof, on or before sixty (60) days following the date upon which Closing
    was to have occurred (and Seller shall not be obligated to reimburse the Transaction Costs until Buyer has so elected or been deemed to have so elected). Notwithstanding the foregoing, nothing contained herein shall limit Buyer&#8217;s remedies at law, in
    equity or as herein provided in the event Seller shall convey or encumber all or any interest in the Property to or in favor of a party other than Buyer in violation of the terms hereof. Except in connection with a claim brought under the preceding
    sentence, each of Seller and Buyer hereby waives any claim for special, punitive, or consequential damages with respect to this Agreement. Nothing in this <u>Section 5.1</u> shall be deemed to limit a party&#8217;s right to recover reasonable third-party
    attorneys&#8217; fees pursuant to <u>Section 11.8</u>.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">21</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">Section 5.2&#160;&#160;&#160;&#160;&#160;&#160; BUYER DEFAULT; LIQUIDATED DAMAGES. IF THE SALE IS NOT CONSUMMATED SOLELY DUE TO A DEFAULT BY BUYER IN
    ITS OBLIGATIONS ON THE CLOSING DATE, THEN THE DEPOSIT SHALL BE DEEMED TO CONSTITUTE A REASONABLE ESTIMATE OF SELLER&#8217;S DAMAGES UNDER THE PROVISIONS OF SECTION 1671 OF THE CALIFORNIA CIVIL CODE AND SELLER SHALL RETAIN THE DEPOSIT AS LIQUIDATED DAMAGES,
    WHICH RETENTION SHALL OPERATE TO TERMINATE THIS AGREEMENT AND RELEASE BUYER FROM ANY AND ALL LIABILITY HEREUNDER EXCEPT FOR THE SURVIVING OBLIGATIONS. SELLER HEREBY WAIVES THE PROVISIONS OF CALIFORNIA CIVIL CODE SECTION 3389. THE PARTIES HAVE AGREED
    THAT DUE TO, AMONG OTHER THINGS, CHANGES IN MARKET CONDITIONS OR FACTS AND CIRCUMSTANCES REGARDING THE PROPERTY, SELLER&#8217;S ACTUAL DAMAGES, IN THE EVENT OF A FAILURE TO CONSUMMATE THIS SALE SOLELY DUE TO BUYER&#8217;S DEFAULT, WOULD BE EXTREMELY DIFFICULT OR
    IMPRACTICABLE TO DETERMINE. BUYER DESIRES TO LIMIT THE AMOUNT OF DAMAGES FOR WHICH BUYER MIGHT BE LIABLE SHOULD THE CLOSING NOT OCCUR AS A RESULT OF BUYER&#8217;S DEFAULT UNDER THIS AGREEMENT. BUYER AND SELLER WISH TO AVOID THE COSTS AND LENGTHY DELAYS WHICH
    WOULD RESULT IF SELLER FILED A LAWSUIT TO COLLECT ITS DAMAGES FOR THE FAILURE OF THE CLOSING DUE TO BUYER&#8217;S DEFAULT IN ITS OBLIGATIONS ON THE CLOSING DATE UNDER THIS AGREEMENT. AFTER NEGOTIATION, THE PARTIES HAVE AGREED THAT, CONSIDERING ALL THE
    CIRCUMSTANCES EXISTING ON THE EFFECTIVE DATE, THE AMOUNT OF THE DEPOSIT IS A REASONABLE ESTIMATE OF THE DAMAGES THAT SELLER WOULD INCUR IN SUCH EVENT. BY PLACING THEIR INITIALS BELOW, EACH PARTY SPECIFICALLY CONFIRMS THE ACCURACY OF THE STATEMENTS MADE
    ABOVE AND THE FACT THAT EACH PARTY WAS REPRESENTED BY <b>WOULD INCUR </b>IN <b>SUCH EVENT. BY PLACING THEIR INITIALS BELOW, EACH PARTY SPECIFICALLY CONFIRMS THE ACCURACY OF THE STATEMENTS MADE ABOVE AND THE FACT THAT EACH PARTY WAS REPRESENTED BY
      COUNSEL WHO EXPLAINED, AT THE TIME THIS AGREEMENT WAS MADE, THE CONSEQUENCES OF THIS LIQUIDATED DAMAGES PROVISION. NOTHING IN Tms SECTION 5.2 SHALL BE DEEMED TO LIMIT SELLER&#8217;S RIGHT TO RECOVER REASONABLE OUT OF POCKET THIRD-PARTY ATTORNEYS&#8217; FEES
      PURSUANT TO SECTION 11.8 BELOW.</b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
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        <td style="width: 9%; font-size: 10pt">&#160;</td>
        <td style="width: 45%; border-bottom: black 1.5pt solid; font-size: 10pt; text-align: center"><font style="font-size: 10pt">/s/KB</font></td>
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        <td style="font-size: 10pt; text-align: center"><font style="font-size: 10pt"><b>SELLER&#8217;S INITIALS</b></font></td>
        <td style="font-size: 10pt; text-align: center">&#160;</td>
        <td style="font-size: 10pt; text-align: center"><font style="font-size: 10pt"><b>BUYER&#8217;S INITIALS</b></font></td>
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  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; color: #1C1C1C"><b>Section 5.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Intentionally Omitted</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C"><font style="font-size: 10pt"><b>Section 5.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;Escrow Instructions.</b></font> The Escrow Holder joins
    in this Agreement to evidence its agreement to act in accordance with the terms and conditions of this Agreement. Further, the following provisions shall control with respect to the rights, duties, and liabilities of the Escrow Holder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">(a)<font style="font: 10pt Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Escrow Holder acts hereunder
    as a depository only and is not responsible or liable in any manner whatsoever for the (i) sufficiency, correctness, genuineness, or validity of any written instrument, notice or evidence of a party&#8217;s receipt of any instruction or notice which is
    received by the Escrow Holder, or (ii) identity or authority of any person executing such instruction notice or evidence.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">(b)<font style="font: 10pt Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Escrow Holder shall have no
    responsibility hereunder except for the performance by it in good faith of the acts to be performed by it hereunder, and the Escrow Holder shall have no liability except for its own willful misconduct or gross negligence.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">(c)<font style="font: 10pt Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Escrow Holder shall be
    reimbursed on an equal basis by Buyer and Seller for any reasonable expenses incurred by the Escrow Holder arising from a dispute with respect to the amount held in escrow, including the cost of any reasonable, out of pocket legal expenses and court
    costs incurred by the Escrow Holder, should the Escrow Holder deem it necessary to retain an attorney with respect to the disposition of the amount held in escrow.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">(d)<font style="font: 10pt Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><font style="font-family: Times New Roman, Times, Serif">In </font>the event of a dispute between the parties hereto with respect to the disposition of the amount held in escrow, the Escrow Holder shall be entitled, at its own discretion, to deliver such amount to an appropriate
    court of law pending resolution of the dispute.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C">(e)<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The Escrow
    Holder shall invest the amount in escrow in accounts which are federally insured, or which invest solely in government securities and shall belong to Buyer other than as set forth in <u>Section</u> 5.2 herein above. Interest earned thereon shall be
    added to the funds deposited by Buyer.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">23</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; color: #1C1C1C"><font style="font-size: 10pt"><b>Section 5.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; Designation of Reporting Person. </b></font><font style="font-family: Times New Roman, Times, Serif">In </font>order to assure compliance with the requirements of <u>Section</u> 6045 of the Internal Revenue Code of 1986, as amended (for purposes of this <u>Section</u> 5.5, the &#8220;<b>Code</b>&#8221;), and
    any related reporting requirements of the Code, the parties hereto agree as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Provided the Escrow Holder shall execute a
    statement in writing (in form and substance reasonably acceptable to the parties hereunder) pursuant to which it agrees to assume all responsibilities for information reporting required under Section 6045(e) of the Code, Seller and Buyer shall
    designate the Escrow Holder as the person to be responsible for all information reporting under Section 6045(e) of the Code (the &#8220;<b>Reporting Person</b>&#8221;). If the Escrow Holder refuses to execute a statement pursuant to which it agrees to be the
    Reporting Person, Seller and Buyer shall agree to appoint another third party as the Reporting Person.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> (b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Seller and Buyer hereby agree:</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>to provide to the Reporting
    Person all information and certifications regarding such party, as reasonably requested by the Reporting Person or otherwise required to be provided by a party to the transaction described herein under Section 6045 of the Code; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>to provide to the Reporting
    Person such party&#8217;s taxpayer identification number and a statement (on Internal Revenue Service Form W-9 or an acceptable substitute form, or on any other form the applicable current or future Code sections and regulations might require and/or any form
    requested by the Reporting Person), signed under penalties of perjury, stating that the taxpayer identification number supplied by such party to the Reporting Person is correct.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Each party hereto agrees to retain this Agreement for not less than four (4) years from the end of the calendar year in which the Closing
    occurred, and to produce it to the Internal Revenue Service upon a valid request therefor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE VI <br>
    REPRESENTATIONS AND WARRANTIES OF SELLER</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 6.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Representations and Warranties of Seller</b>. Subject to the provisions of <u>Section 6.2</u>, Seller
    makes the following representations and warranties with respect to the Property as of the date hereof and as of Closing:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Status</u>. Seller is a corporation duly
    organized, validly existing and in good standing under the laws of the State of Delaware and is qualified to transact business in the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Authority</u>. The execution and delivery of
    this Agreement (and all ancillary documents delivered pursuant hereto including, without limitation, the Closing Documents) by Seller and the performance of its obligations hereunder and thereunder have been or will be duly authorized by all necessary
    action on the part of Seller, and this Agreement constitutes the legal, valid, and binding obligation of Seller, subject to equitable principles and principles governing creditors&#8217; rights generally.</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Non-Contravention</u>. The execution and
    delivery of this Agreement by Seller and the consummation of the transactions by Seller contemplated hereby or in the other Closing Documents will not (i) violate any judgment, order, injunction, decree, regulation or ruling of any court or
    Governmental Entity, or (ii) conflict with, result in a breach of, or constitute a default under the organizational documents (including any amendments thereto) of Seller, any note or other evidence of indebtedness, any mortgage, deed of trust or
    indenture, or any lease or other material agreement or instrument to which Seller is a party or by which Seller may be bound.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Suits and Proceedings</u>. Except as set
    forth on attached <b><u>Exhibit C</u></b>, there are no legal actions, suits or similar proceedings at law, in equity, or otherwise pending and served or threatened in writing against Seller (with respect to the Property, as opposed to actions against
    Seller as a going concern) or the Property which would be reasonably likely to adversely affect, individually or in the aggregate, (i) the ability of Seller to perform its obligations hereunder, or (ii) the ownership or operation of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Non-Foreign Entity</u>. Seller is not a
    &#8220;foreign person&#8221; or &#8220;foreign corporation&#8221; as those terms are defined in the Internal Revenue Code of 1986, as amended, and the regulations promulgated thereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Consents</u>. No consent, waiver, approval,
    or authorization is required from any Person (that has not already been obtained) in connection with the execution and delivery of this Agreement by Seller or the performance by Seller of the transactions contemplated hereby.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Condemnation</u>. Seller has no knowledge of
    and has not received any written notice of any pending or contemplated condemnation or action in eminent domain from a Governmental Entity with respect to all or part of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(h)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Bankruptcy</u>. Seller has not (i) commenced
    a voluntary case, or had entered against it a petition, for relief under any federal bankruptcy act or any similar petition, order or decree under any federal or state law or statute relative to bankruptcy, insolvency or other relief for debtors, (ii)
    caused, suffered or consented to the appointment of a receiver, trustee, administrator, conservator, liquidator or similar official in any federal, state or foreign judicial or non-judicial proceedings, to hold, administer and/or liquidate all or
    substantially all of its property, or (iii) made an assignment for the benefit of creditors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Governmental Notices</u>. Except as set
    forth on attached <b><u>Exhibit C</u></b> or included in the Due Diligence Items made available on or prior to the Effective Date, Seller has no knowledge of and has not received written notice from any Governmental Entity of (i) any pending or
    threatened zoning, building, fire, or health code violations or violations of other governmental requirements, laws, policies or regulations with respect to the Property that have not previously been corrected, (ii) violations with respect to the Title
    Documents that have not previously been corrected, or (iii) violation of any applicable laws, ordinances, rules, requirements, regulations or codes of any governmental agency, body or subdivision thereof bearing on the Property.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(j)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Contracts</u>. Except as set forth on
    attached <b><u>Exhibit C</u></b> and any agreements expressly disclosed as exceptions on the Title Commitment, there are no property management contracts, real property service contracts, construction contracts, reciprocal easement agreements, or any
    other contracts related to the leasing, subleasing, ownership, operation, maintenance, construction or development of any part of the Property to which Seller is a party, or, to Seller&#8217;s knowledge, to which any other Person is a party, which would be
    binding on Buyer after Closing.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(k)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;</font><u>Leases</u>. Other than the Buyer-Seller
    Lease to be entered into at Closing, there are no Leases in effect granting any party the right to use or occupy any portion of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(l)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;&#160;</font><u>Environmental</u>. Except as set forth on
    attached <b><u>Exhibit C</u></b> or included in the Due Diligence Items made available on or prior to the Effective Date, Seller represents that Seller has not received written notice of nor is Seller actually aware of: (i) any actual or alleged
    violation of, or obligations or liability under, any applicable Environmental Laws with respect to the Property or operation at the Property; (ii) any existing, pending, anticipated, or threatened investigation of or pending, anticipated or threatened
    claims against Seller or the Property by any Governmental Entity or third party; (iii) the presence of Hazardous Materials on, under, above or emanating to or from, or having emanated to or from the Property or, to Seller&#8217;s knowledge, in the vicinity
    of the Property; (iv) any remedial obligations with respect to Seller or the Property under any Environmental Laws; (v) any Known Environmental Condition or Unknown Environmental Condition; (vi) any noncompliance, anticipated noncompliance, or
    threatened noncompliance of the Property or its operation with any Environmental Law, including any Permits or Licenses; or (vii) any Permits or Licenses required with respect to the Property or operation at the Property. Seller has delivered or
    otherwise made available all material and final reports and correspondence with Governmental Entities in Seller&#8217;s possession or control relating to the environmental condition of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> (m)&#160;&#160;&#160; &#160;&#160;&#160;&#160; <u>Anti-Money Laundering, Anti-Terrorism and Sanctions Laws</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller is aware of, and
    acknowledges its obligations under, the Anti-Corruption Laws and Anti-Money Laundering, Anti-Terrorism and Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>At all times while this
    Agreement is in effect, Seller shall comply with all applicable Anti-Corruption, Anti-Terrorism, Anti-Money Laundering and Sanctions Laws. Without limiting the foregoing, Seller covenants that it shall not use any amounts paid pursuant to this
    Agreement to lend, contribute or otherwise make available such proceeds to any Sanctioned Person or for any use in violation of applicable Anti-Corruption, Anti-Terrorism, Anti-Money Laundering or any Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller maintains, and
    covenants to continue to maintain during the term of this Agreement, compliance policies, procedures and internal controls designed to ensure compliance with applicable Anti-Corruption, Anti-Terrorism, Anti-Money Laundering and Sanctions Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iv)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Neither Seller, any Seller
    Control Affiliate or, to Seller&#8217;s knowledge, any Seller Significant Owner or Seller Representative: (i) is listed on any Government/Sanctions List; (ii) is a Sanctioned Person or otherwise the subject of any Sanctions; (iii) is or has been the subject
    of any investigation relating to Sanctions; (iv) has been found by a Sanctions Authority to have been engaged in sanctionable conduct under any Sanctions; (v) has directly or indirectly conducted, conducts or is otherwise involved with any business
    with or involving any sanctioned government (or any sub-division thereof), or any Person that is the subject of Sanctions or is located in any country that is the subject of Sanctions; (vi) directly or indirectly supports or facilitates, or plans to
    support or facilitate or otherwise become involved with, any such Person, government, entity or project; or (vii) has taken or failed to take any action that would cause it to be in non-compliance with any Anti-Corruption, Anti-Terrorism, Anti-Money
    Laundering or Sanctions Laws;&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">26</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(v)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;No action, suit, investigation or
      proceeding relating to any Anti-Corruption, Anti-Terrorism, Anti-Money Laundering, or Sanctions Laws involving Seller or any Seller Control Affiliate is pending or, to Seller&#8217;s knowledge, threatened. To Seller&#8217;s knowledge, no action, suit,
      investigation or proceeding relating to any Anti-Corruption, Anti-Terrorism, Anti-Money Laundering, or Sanctions Laws involving any Seller Significant Owner or any Seller Representative is pending or threatened;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(n)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Due Diligence Items</u>. The Due Diligence
    Items delivered to Buyer are in all material respects true, correct and complete originals or copies of the versions of the Due Diligence Items. Seller has not received written notice from any Person that any information in the Due Diligence Items is
    not true, accurate or complete. To Seller&#8217;s knowledge, Seller has delivered or made available to Buyer all of the Due Diligence Items in its possession or control that could be reasonably expected to have a material effect on the operations, use,
    condition, or value of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(o)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Tax Appeals</u>. Seller has not filed any
    tax certiorari or other appeals with respect to the Property which remain outstanding.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(p)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>ROFOs/ROFRs</u>. Neither Seller nor its
    direct or indirect owners have granted any outstanding exclusive negotiation period, purchase option, right of first refusal to purchase, right of first offer to purchase or similar right to purchase in connection with all or any portion of the
    Property (or any direct or indirect interests therein [other than with respect to indirect interests constituting publicly-traded securities]), except in favor of Buyer.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(q)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Defaults</u>. Seller is not in default and,
    to Seller&#8217;s knowledge, no other party is in default under any declaration or covenant recorded against title to the Property, and no event has occurred which, with the giving of notice or passage of time or both, would constitute a default thereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(r)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Warranties</u>. Attached hereto as <u>Exhibit







      E</u> is a true, complete, correct and complete list of all material warranties or guaranties issued in connection with the development, construction, operation, maintenance or repair of the Property, and all amendments and modifications thereto,
    which are currently in effect (collectively, the &#8220;<b>Warranties</b>&#8221;). True and correct copies of all of the Warranties have been delivered to Buyer. To Seller&#8217;s knowledge, the Warranties are in full force and effect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(s)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Seller Knowledge Parties</u>. Seller
    represents and warrants that the Seller Knowledge Parties are the most knowledgeable employees of Seller with respect to (i) the representations and warranties made by Seller under this Agreement, (ii) the Property, and (iii) the transaction
    contemplated by this Agreement.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">27</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 6.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Limited Liability</b>. The representations and warranties of Seller set forth in <u>Section 6.1</u>
    of this Agreement will survive the Closing for a period expiring on the date that is nine (9) months after the Closing (unless Buyer has given written notice to Seller of a breach of any such representation or warranty (specifying the specific claim
    and breach) prior to the expiration of the nine (9) month period following Closing, in which event Buyer&#8217;s right to recover amounts from Seller for such noticed breach of a representation or warranty shall survive such period). Buyer will not have any
    right to bring any action against Seller as a result of any untruth or inaccuracy of such representations and warranties unless and until the aggregate amount of all liability and losses arising out of any such untruth or inaccuracy exceeds Twenty Five
    Thousand and 00/100 Dollars ($25,000.00) (the &#8220;<b>Basket</b>&#8221;) in which event Buyer may claim indemnification for the full amount of such claim(s) up to the Indemnification Cap (as defined below), and Seller&#8217;s liability for any untruth or inaccuracy of
    such representations and warranties shall not exceed, in the aggregate, one percent (1%) of the Purchase Price (the &#8220;<b>Indemnification Cap</b>&#8221;); it being understood and agreed, however, that such Basket and Indemnification Cap shall not apply to and
    shall expressly exclude Seller&#8217;s liabilities under <u>Section 9.5</u> (Prorations and Closing Costs), <u>Section 9.6</u> (Brokers) and <u>Section 9.8</u> (Tax Protests; Tax Refunds and Credits). Seller shall have no liability with respect to any of
    Seller&#8217;s representations, warranties and covenants herein if, prior to the Closing, Buyer is &#8220;deemed to know&#8221; of such breach of a representation, warranty or covenant of Seller herein and Buyer nevertheless consummates the transaction contemplated by
    this Agreement. Buyer shall be &#8220;deemed to know&#8221; of such a breach if: (i) it is disclosed in this Agreement or any Exhibit or Schedule hereto; (ii) it is disclosed in the Due Diligence Items or other information that is in the Data Room not less than
    two (2) business days before the Closing; (iii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>it is disclosed in any written reports obtained by Buyer before the Closing; or (iv) it is within the actual knowledge of the Buyer
    Designated Person (as hereinafter defined) before the Closing. The provisions of this <u>Section 6.2</u> shall survive the Closing or any earlier termination of this Agreement and delivery of the Deed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 6.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; Knowledge Parties<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>If a representation, warranty or other statement
    is made in this Agreement or in any document or instrument to be delivered at Closing pursuant to this Agreement, on the basis of the &#8220;knowledge,&#8221; &#8220;actual knowledge&#8221; or &#8220;best of knowledge&#8221; (or similar phrases) of Seller then such representation,
    warranty or other statement is made based on the actual, current, conscious express awareness of facts or other information of Elizabeth L. Hougen, EVP &amp; CFO (&#8220;<b>Seller Knowledge Parties</b>&#8221;), as distinguished from implied, imputed and/or
    constructive knowledge, as of the Effective Date and as of any time thereafter up to and including the Closing, and without undertaking any special inquiry or investigation by such person(s). Seller is not under a duty of inquiry or investigation in
    order to make any such representation, warranty, or other statement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>If a representation, warranty or other statement
    is made in this Agreement or in any document or instrument to be delivered at Closing pursuant to this Agreement, on the basis of the &#8220;knowledge,&#8221; &#8220;actual knowledge&#8221; or &#8220;best of knowledge&#8221; (or similar phrases) of Buyer then such representation,
    warranty or other statement is made based on the actual, current, conscious express awareness of facts or other information of Tycho Suter (&#8220;<b>Buyer Designated Person</b>&#8221;), as distinguished from implied, imputed and/or constructive knowledge, as of
    the Effective Date and as of any time thereafter up to and including the Closing, and without undertaking any special inquiry or investigation by such person(s). Buyer represents and warrants to Seller that such individuals are the persons most
    knowledgeable in connection with the representations and warranties made by Buyer under this Agreement. Buyer is not under a duty of inquiry or investigation in order to make any such representation, warranty, or other statement.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">28</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 6.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;Liability of Representations and Warranties</b>. The parties acknowledge that the individuals named
    above are named solely for the purpose of defining and narrowing the scope of Seller&#8217;s and Buyer&#8217;s knowledge, as applicable, and not for the purpose of imposing any liability on or creating any duties running from such individuals to the counterparty
    under this Agreement, as applicable. Each of Seller and Buyer covenants that it will bring no action of any kind against such individuals, as applicable, or related to or arising out of these representations and warranties.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 6.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notice of Breaches of Representations and Warranties</b>. Seller shall promptly notify Buyer in writing
    of any changed condition, receipt of notice or documentation, or acquired knowledge, that would cause any material inaccuracy of any representation or warranty of Seller contained herein (any such changed condition, received notice or documentation, or
    acquired knowledge being defined as a &#8220;<b>Changed Condition</b>&#8221;). Buyer shall promptly notify Seller in writing of any material inaccuracy in any representation or warranty of Seller contained herein of which Buyer obtains knowledge (within the
    meaning of <u>Section 6.3(b)</u>) prior to the Close of Escrow (&#8220;<b>Known Misrepresentation</b>&#8221;). Within three (3) Business Days after either notification in writing by Seller to Buyer of any such Changed Condition or notification by Buyer to Seller
    of any Known Misrepresentation, Seller, at Seller&#8217;s own option and expense, may elect by written notice to Buyer to remedy the Changed Condition or Known Misrepresentation such that Seller&#8217;s representations have no material inaccuracy, and the Closing
    Date may be extended for up to fifteen (15) calendar days after the scheduled Closing Date in order for Seller to effectuate such remedy. If Seller does not elect to effectuate such remedy so as to cause Seller&#8217;s representations to have no material
    inaccuracy, or if Seller so elects but then fails to complete such remedy within such fifteen (15) day period, then Buyer may elect, by written notice to Seller given at any time thereafter, to terminate this Agreement, in which event (i) neither Buyer
    nor Seller shall have any further obligation under this Agreement, except for the Surviving Obligations, (ii) the Deposit shall be promptly returned to Buyer by Escrow Holder and Seller shall reimburse Buyer for its Transaction Costs, and (iii) if such
    Changed Condition resulted from Seller&#8217;s intentional acts or breach of its obligations herein and was not cured by Seller pursuant to the provisions above, then Seller shall be in breach of a material obligation under this Agreement and Buyer shall
    have the remedies set forth in <u>Section 5.1</u>. If, notwithstanding Seller&#8217;s election not to effectuate such remedy (or Seller&#8217;s failure to complete such remedy within such fifteen (15) day period, Buyer elects to consummate the purchase of the
    Property, Seller shall not be liable to Buyer as a result of any inaccuracy in any representation or warranty of Seller contained herein that results from such Changed Condition or Known Misrepresentation identified in any such written notice from one
    party to the other.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">29</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE VII <br>
    REPRESENTATIONS AND WARRANTIES OF BUYER</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><b>Section 7.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Buyer&#8217;s Representations and Warranties</b>. Buyer represents and warrants to Seller the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Status</u>. Buyer is a limited liability
    company duly organized or formed, validly existing and in good standing under the laws of the State of Delaware and is qualified to transact business in the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Authority</u>. The execution and delivery of
    this Agreement and the performance of Buyer&#8217;s obligations hereunder have been or will be duly authorized by all necessary action on the part of Buyer and this Agreement constitutes the legal, valid, and binding obligation of Buyer, subject to equitable
    principles and principles governing creditors&#8217; rights generally.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Non-Contravention</u>. The execution and
    delivery of this Agreement by Buyer and the consummation by Buyer of the transactions contemplated hereby will not violate any judgment, order, injunction, decree, regulation or ruling of any court or Governmental Entity or conflict with, result in a
    breach of, or constitute a default under the organizational documents (including any amendments thereto) of Buyer, any note or other evidence of indebtedness, any mortgage, deed of trust or indenture, or any lease or other material agreement or
    instrument to which Buyer is a party or by which it is bound.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Consents</u>. No consent, waiver, approval,
    or authorization is required from any Person (that has not already been obtained or, in the case of authorization by Buyer and its direct and indirect members, will be obtained prior to the Closing) in connection with the execution and delivery of this
    Agreement by Buyer or the performance by Buyer of the transactions contemplated hereby.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Bankruptcy</u>. Buyer has not (i) commenced a
    voluntary case, or had entered against it a petition, for relief under any federal bankruptcy act or any similar petition, order or decree under any federal or state law or statute relative to bankruptcy, insolvency or other relief for debtors, (ii)
    caused, suffered or consented to the appointment of a receiver, trustee, administrator, conservator, liquidator or similar official in any federal, state or foreign judicial or non-judicial proceeding, to hold, administer and/or liquidate all or
    substantially all of its property, or (iii) made an assignment for the benefit of creditors.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Patriot Act</u>. Buyer is in compliance with
    all applicable anti-money laundering and anti-terrorist laws, regulations, rules, executive orders and government guidance, including the reporting, record keeping and compliance requirements of the Bank Secrecy Act, as amended by The International
    Money Laundering Abatement and Financial Anti-Terrorism Act of 2001, Title III of the Patriot Act, and other authorizing statutes, executive orders and regulations administered by OFAC, and related Securities and Exchange Commission, SRO or other
    agency rules and regulations, and has policies, procedures, internal controls and systems that are reasonably designed to ensure such compliance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>OFAC</u>. None of: (i) Buyer, any direct
    Affiliate of Buyer nor any Person controlled by Buyer; nor (ii) any Person who owns a controlling interest in or otherwise controls Buyer; nor (iii) to the best of knowledge of Buyer, after making due inquiry, if Buyer is a privately held entity, any
    Person otherwise having a direct or indirect beneficial interest (other than with respect to an interest in a publicly traded entity or beneficiaries of a pension plan that holds indirect interests in Buyer) in Buyer; nor (iv) any Person for whom Buyer
    is acting as agent or nominee in connection with this investment, is a country, territory, Person, organization, or entity named on an OFAC List, nor is a prohibited country, territory, Person, organization, or entity under any economic sanctions
    program administered or maintained by OFAC.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">30</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE VIII&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>INTERIM OPERATING COVENANTS</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.1&#160;&#160;&#160;&#160;&#160;&#160; Buyer-Seller Lease</b>. The parties acknowledge and agree that, pursuant and subject to the terms of
    the Buyer-Seller Lease, Seller, as tenant thereunder, shall occupy the Property from and after Closing without interruption. Seller shall have no obligation to remove any personal property or otherwise vacate or discontinue use of the Property upon or
    after Closing, or to make repairs or improvements to the Property before, upon or following Closing, except as expressly provided in this Agreement or in the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;Operation of Property</b>. Seller, from and after the Effective Date up to and including the Closing
    Date: (i) shall maintain and repair the Property in substantially the same condition as the Property exists as of the Effective Date, reasonable wear and tear excepted; and (ii) shall continue to manage the Property in substantially the same manner as
    the Property is managed as of the Effective Date and shall not defer maintenance or otherwise change its current operating procedures. Furthermore, from and after the Effective Date up to and including the Closing Date, Seller shall comply with all
    covenants, conditions, restrictions, easements, rights of way and other rights of third parties relating to the Property. Seller hereby covenants that, from the Effective Date up to and including the Closing Date, without the express prior written
    consent of Buyer, which may be granted or withheld in Buyer&#8217;s sole but reasonable discretion, Seller shall not, directly or indirectly, grant or otherwise create, allow, or consent to the creation of any easement, restriction, lien, assessment or
    encumbrance respecting the Property or the operation at the Property, including without limitation, any lease, license or other contract affecting the Property in any material respect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;Insurance</b>. From and after the Effective Date through the Closing Date, Seller shall carry and
    maintain in full force and effect, at its sole cost and expense, the policies now in effect, including, without limitation, any fire and extended coverage insurance policies (or substitute policies in equal or greater amounts).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;Transfers/Leases</b>. From and after the Effective Date through the Closing Date, Seller shall not
    sell, assign, or transfer any interest or option in any portion of the Property nor shall Seller enter into any lease, license, occupancy agreement or other agreement, document or instrument permitting any third party to occupy any portion of the
    Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;Alterations</b>. From and after the Effective Date to the Closing Date, Seller shall not make or permit
    any capital improvements (or other improvements and alterations which would require Buyer&#8217;s consent as &#8220;Landlord&#8221; under the Buyer-Seller Lease) to any portion of the Property, without the express written consent of Buyer, which may be granted or
    withheld in Buyer&#8217;s sole but reasonable discretion.&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">31</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.6&#160;&#160;&#160;&#160;&#160;&#160; New Contracts</b>. Seller is not party to and will not enter into any service, supply, equipment rental
    and/or other service contracts related to the operation of the Property or other contract that will be an obligation affecting the Property or operation at the Property subsequent to Closing, except (i) contracts expressly approved by Buyer in its sole
    and absolute discretion or entered into in the ordinary course of business that are terminable without cause and without the payment of any termination penalty on not more than thirty (30) days&#8217; prior notice, and (ii) contracts that the Seller is
    either required or permitted to maintain in its own name under the terms of the Buyer-Seller Lease. Seller shall not permit any mortgages, deeds of trust or other encumbrances to be recorded against title to the Property without Buyer&#8217;s prior written
    consent, which may be given or withheld in Buyer&#8217;s sole and absolute discretion.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 8.7&#160;&#160;&#160;&#160;&#160;&#160; Warranty Transfer</b>. With respect to any Warranties in effect on the Closing Date, Seller shall: (i)
    deliver written notice to any party (&#8220;<b>Warrantor</b>&#8221;) that is liable for each Warranty that is being assigned to Buyer pursuant to this Agreement that such Warranty is being assigned, (ii) use commercially reasonable efforts to cause the Warrantor
    to deliver to Seller all forms and other requirements for the assignment of the Warranty, if any (&#8220;<b>Warranty Assignment Package</b>&#8221;), and (iii) execute the necessary documents in the Warranty Assignment Package and take any other actions that are
    reasonably necessary to assign the respective Warranty in accordance with the procedures of the respective Warrantor. To the extent that any Warranty is not transferred to Buyer at or prior to the Closing as aforesaid, such failure shall not be deemed
    a default by Seller of this Agreement or otherwise entitle Buyer to terminate this Agreement, but Seller shall continue to use commercially reasonable efforts following the Closing to take actions reasonably necessary to assign the respective Warranty
    to Buyer and shall enforce any such Warranty on Buyer&#8217;s behalf at the direction of Buyer. This <u>Section</u> 8.7 shall survive the Closing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE IX <br>
    CLOSING AND CONDITIONS</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.1&#160;&#160;&#160;&#160;&#160;&#160; Escrow Instructions</b>. Upon execution of this Agreement, the parties hereto shall deposit an executed
    counterpart of this Agreement with the Escrow Holder, and this Agreement shall serve as escrow instructions to the Escrow Holder as the escrow holder for consummation of the purchase and sale contemplated hereby. Seller and Buyer agree to execute such
    reasonable additional and supplementary escrow instructions as may be appropriate to enable the Escrow Holder to comply with the terms of this Agreement; provided, however, that in the event of any conflict between the provisions of this Agreement and
    any supplementary escrow instructions, the terms of this Agreement shall control.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 9.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; Closing<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><b>Closing</b>. The closing hereunder (&#8220;<b>Closing</b>&#8221;
    or &#8220;<b>Close of Escrow</b>&#8221;) shall be held and delivery of all items to be made at the Closing under the terms of this Agreement shall be made through escrow at Escrow Holder&#8217;s office on the Closing Date. At least two (2) Business Days prior to the
    Closing Date, Buyer shall request that the Escrow Holder prepare and deliver to Buyer and Seller a preliminary closing statement (the &#8220;<b>Closing Statement</b>&#8221;). On the Closing Date, Buyer shall deposit in escrow with the Escrow Holder the Purchase
    Price (subject to adjustments described in <u>Section 9.5</u>), together with all other costs and amounts to be paid by Buyer at the Closing pursuant to the terms of this Agreement, by Federal Reserve wire transfer of immediately available funds to an
    account to be designated by the Escrow Holder. No later than 3:00 p.m. Pacific Time on the Closing Date and provided all conditions to Closing set forth in <u>Section 9.2(c)</u> have been satisfied, or waived or deemed waived by Buyer, (A) Buyer and
    Seller will authorize the Escrow Holder to (i) pay to Seller by Federal Reserve wire transfer of immediately available funds to an account designated by Seller, the Purchase Price (subject to adjustments described in Section 9.5), less any costs or
    other amounts to be paid by Seller at Closing pursuant to the terms of this Agreement and the Closing Statement, and (ii) pay all appropriate payees the other costs and amounts to be paid by Buyer at Closing pursuant to the terms of this Agreement, and
    (iii) record the Deed and distribute fully-executed copies of all Closing Documents to each of Buyer and Seller, and (B) to otherwise pay to the appropriate payees out of the proceeds of Closing payable to Seller all costs and amounts to be paid by
    Seller at Closing pursuant to the terms of this Agreement.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><b>Seller Closing Conditions</b>. It shall be a
    condition precedent to Seller&#8217;s obligation to sell the Property that:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>all of Buyer&#8217;s
    representations and warranties contained in or made pursuant to this Agreement shall be true and correct in all material respects as of the Closing Date;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>there shall be no material
    breach of Buyer&#8217;s covenants and obligations set forth in this Agreement; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Buyer shall have delivered
    the items described in <u>Section 9.4</u> to Seller or to Escrow Holder, as applicable.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">It is understood and agreed that Seller may waive any such condition precedent in Seller&#8217;s sole and absolute discretion. In the event any such
    condition is not timely satisfied or waived by Seller, then the same shall be a material breach of this Agreement by Buyer and Seller shall have the remedies set forth in <u>Section 5.2</u>. Buyer hereby covenants that it shall exercise reasonable and
    diligent efforts to cause the conditions set forth in this <u>Section 9.2(b)</u> and the condition set forth in <u>Section 9.2(c)(iv)</u> below to be fully satisfied by the Closing Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><b>Buyer Closing Conditions</b>. The following
    shall each constitute a condition precedent to Buyer&#8217;s obligation to consummate the Closing hereunder:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>all of Seller&#8217;s
    representations and warranties contained in or made pursuant to this Agreement shall be true and correct in all material respects as of the Closing Date;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>there shall be no material
    breach of Seller&#8217;s covenants and obligations set forth in this Agreement;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller shall have delivered
    the items described in <u>Section 9.3</u> to Buyer or to Escrow Holder, as applicable;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(iv)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>the Title Company shall be
    unconditionally and irrevocably committed to issue the Title Policy (subject only to the payment of the premium, satisfaction of all requirements set forth in the Title Commitment that are the sole responsibility of Buyer to satisfy [and Buyer&#8217;s
    satisfaction of its part of any joint requirements, if any], delivery by Buyer to the Title Company of all documents and instruments requested by the Title Company from Buyer and payment of all other amounts specified in this Agreement to be paid by
    Buyer) showing no exceptions other than the Permitted Exceptions;&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(v)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>subject to <u>Section 10.1</u>,
    the Property shall be in substantially the same condition as it existed on the Effective Date, subject to ordinary wear and tear;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in"> (vi)&#160;&#160;&#160;&#160;&#160; the Development Conditions have been satisfied;</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(vii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;</font>there is no pending or
    threatened review or appeal of, and there is no right to review or appeal the Entitlements by any Governmental Entity or Person other than Buyer;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(viii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;</font>there is no pending or
    threatened moratorium on development of the Property; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in; margin-left: 0.5in">(ix)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>there is no pending or
    threatened governmental or quasi-governmental action which does not constitute a pending or threatened moratorium (which is addressed in clause (viii) above) which could reasonably be expected to prohibit or delay Buyer&#8217;s development of the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">It is understood and agreed that Buyer may waive any such condition precedent in Buyer&#8217;s sole and absolute discretion; and
    Buyer&#8217;s failing to terminate this Agreement prior to the Closing shall be deemed to constitute Buyer&#8217;s waiver of such conditions precedents; provided, however, nothing set forth herein shall constitute a waiver of Buyer&#8217;s post-Closing remedies for any
    Changed Condition of which Buyer was not deemed to know (within the meaning of <u>Section 6.3</u>) prior to the Closing. In the event any such condition is not timely satisfied or waived by Buyer, then Buyer shall have the right to terminate this
    Agreement by written notice to Seller and Escrow Holder, in which event, Buyer shall be entitled to the immediate return of the Deposit; provided, however, that, to the extent, any of the condition precedents set forth in sub-sections (i), (ii), (iii),
    and (v), is not satisfied, Buyer shall also receive a reimbursement of its Transaction Costs. Seller hereby covenants that it shall exercise reasonable and diligent efforts to cause the conditions set forth in this <u>Section 9.2(c)</u> to be fully
    satisfied by the Closing Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; Seller&#8217;s Closing Documents and Other Items</b>. At or before Closing, Seller shall deposit into escrow
    the following items:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;a duly executed and acknowledged Grant Deed in the form of attached <b><u>Exhibit F </u></b>(the &#8220;<b>Deed</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>two (2) duly executed counterparts of the
    Buyer-Seller Lease, one (1) duly executed and acknowledged counterpart of a memorandum of the Buyer-Seller Lease and at least one (1) original of any other agreements, documents or instruments contemplated by the Buyer-Seller Lease to be executed and
    delivered by Seller, as tenant, in connection therewith;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; an executed California Form 593 Real Estate Withholding Certificate;&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">34</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>two (2) duly executed counterparts of a Bill of
    Sale and Assignment and Assumption Agreement in the form of attached <b><u>Exhibit H</u></b> (the &#8220;<b>Assignment</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>an affidavit pursuant to <u>Section</u>
    1445(b)(2) of the Code, on which Buyer is entitled to rely, that Seller (or, if Seller is a disregarded entity for federal income tax purposes, the person treated as the owner of the Property for such purposes) is not a &#8220;foreign person&#8221; within the
    meaning of Section 1445(f)(3) of the Code in the form attached as <b><u>Exhibit L</u></b> (&#8220;<b>FIRPTA Certificate</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>documentation to establish to the Title
    Company&#8217;s satisfaction the due authority of Seller&#8217;s disposition of the Property and Seller&#8217;s delivery of the documents required to be delivered by Seller pursuant to this Agreement (including, but not limited to, the organizational documents of
    Seller, as they may have been amended from time to time, resolutions of Seller and incumbency certificates of Seller);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>a duly executed certificate, stating that each of
    the representations and warranties of Seller set forth in this Agreement are, as of the Closing Date, true and accurate in all material respects, duly authorized and executed by Seller, in the form of attached <b><u>Exhibit I</u></b> (the &#8220;<b>Seller&#8217;s
      Certificate</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> (h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a duly executed title affidavit in the form of <b><u>Exhibit K</u></b> (the &#8220;<b>Owner&#8217;s Affidavit</b>&#8221;);</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>if any plats or approvals required in
    connection with the Entitlements are to be recorded at or immediately after the Closing, the final executed plat or approvals in form for recording according to applicable law;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(j)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>any consents then-obtained by Seller in order
    to transfer the Warranties to Buyer, subject to <u>Section 8.7</u> above;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> (k)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a counterpart signature to the Closing Statement executed by Seller; and</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(l)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>such other documents as may be reasonably
    required by the Title Company or as may be agreed upon by Seller and Buyer to consummate the purchase of the Property as expressly contemplated by this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><b>Section 9.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; Buyer&#8217;s Closing Documents and Other Items</b>. At or before Closing, Buyer shall deposit into escrow the following items:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>the balance of the Purchase Price, subject to
    prorations and adjustments set forth in this Agreement, and such additional funds as are necessary to close this transaction;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>two (2) duly executed counterparts of the
    Buyer-Seller Lease, one (1) duly executed and acknowledged counterpart of a memorandum of the Buyer-Seller Lease and at least one (1) original of any other agreements, documents or instruments contemplated by the Buyer-Seller Lease to be executed and
    delivered by Buyer, as landlord, in connection therewith;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c) &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;two (2) duly executed counterparts of the Bill of Sale and Assignment;&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">35</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>documentation to establish to Title Company&#8217;s
    reasonable satisfaction the due authority of Buyer&#8217;s acquisition of the Property and Buyer&#8217;s delivery of the documents required to be delivered by Buyer pursuant to this Agreement (including, but not limited to, the organizational documents of Buyer,
    as they may have been amended from time to time, resolutions of Buyer and incumbency certificates of Buyer);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>a duly executed certificate, stating that each of
    the representations and warranties of Buyer set forth in this Agreement are, as of the Closing Date, true and accurate in all material respects, duly authorized and executed by Buyer, in the form of attached <b><u>Exhibit J</u></b> (the &#8220;<b>Buyer&#8217;s
      Certificate</b>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> (f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;a counterpart signature to the Closing Statement executed by Buyer;</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(g)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>a duly completed and signed Preliminary Change of
    Ownership Report (pursuant to California Revenue &amp; Taxation Code Section 480.3) for the Property; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(h)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>such other documents as may be reasonably
    required by the Title Company or as may be agreed upon by Seller and Buyer to consummate the purchase of the Property as contemplated by this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">Section 9.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; Prorations and Closing Costs<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Real estate and personal property taxes,
    utilities and all other proratable items shall remain the responsibility of Seller pursuant to the Buyer-Seller Lease and all payments of the same that may be due and payable as of Closing shall remain Seller&#8217;s responsibility; provided, however, that
    solely for accounting purposes, all such proratable items paid by Seller upon Closing but attributable to amounts accruing on and after of 12:01 a.m. Pacific Time on the Closing Date shall be credited to Seller&#8217;s obligation to pay such expenses as the
    &#8220;tenant&#8221; under the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Seller shall pay (a) one-half (1/2) of Escrow
    Holder&#8217;s escrow fee, (b) the document-drafting and recording charges for the Deed, (c) all city and county documentary transfer taxes required by law, (d) the costs for all title insurance search fees and commitment fees, and all premiums for the Title
    Policy and costs of any curative endorsements to remove certain disapproved title matters thereto, and (e) the cost of any Seller&#8217;s Required Removal Items. Buyer shall pay (i) one-half (1/2) of Escrow Holder&#8217;s escrow fee, (ii) all document-drafting and
    recording charges for any loan documents for Buyer, (iii) the cost of all third party studies and reports obtained by Buyer in connection with Buyer&#8217;s inspections and investigation, (iv) the cost for any Title Policy endorsements requested by Buyer,
    and (v) any other costs customarily charged Buyers in the City of Carlsbad. If Escrow fails to close due to either Party&#8217;s default, then defaulting Party shall pay all Escrow cancellation and title charges. If Escrow fails to close for any reason other
    than the foregoing, Buyer and Seller shall each pay one-half (&#189;) of all Escrow cancellation and title charges, which means all fees, charges and expenses incurred by Escrow Holder, including all expenses incurred in connection with issuance of the
    Preliminary Report and other title matters. All other closing costs shall be allocated as is customary in the City of Carlsbad. Except as expressly set forth otherwise in this Agreement, each Party shall pay its own legal fees.&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">36</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Brokers</b>. Buyer and Seller covenant and represent to each other that, to their knowledge, there is
    no party entitled to a real estate commission, finder&#8217;s fee, cooperation fee, or other brokerage-type fee or similar compensation in connection with this Agreement and the transactions contemplated hereby other than CBRE, Inc. Each party agrees to
    defend, indemnify, and hold the other party, its employees, representatives and agents safe and harmless from and against any and all such Claims from any other broker, agent, individual or entity claiming by or though the indemnifying party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.7&#160;&#160;&#160;&#160;&#160;&#160; Expenses</b>. Except as provided in <u>Sections 9.5</u> and <u>9.6</u>, each party hereto shall pay
    its own expenses incurred in connection with this Agreement and the transactions contemplated hereby, including, without limitation in the case of Buyer, all third-party engineering and environmental review costs and all other due diligence costs.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 9.8&#160;&#160;&#160;&#160;&#160;&#160; Tax Protests; Tax Refunds and Credits</b>. Seller shall have the right to control the progress of and
    to make all decisions with respect to any contest of the real estate taxes and personal property taxes for the Real Property due and payable during all tax years through and including the tax year in which the Closing occurs (the &#8220;<b>Closing Tax Year</b>&#8221;);






    provided Seller shall keep Buyer fully informed regarding the status of any contest with respect to the taxes attributable to such period. To the extent any real estate or personal property tax refunds or credits are received after Closing with respect
    to the Property and such refunds or credits are attributable to real estate and personal property taxes paid for any tax year prior to and including the Closing Tax Year, Seller shall be entitled to the entirety of such refunds and credits. Any contest
    of the real estate taxes and personal property taxes for the Property due and payable for all years subsequent to the Closing Tax Year, and any real estate or personal property tax refunds or credits attributable to such period, shall be governed by
    the terms of the Buyer-Seller Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE X <br>
    CASUALTY AND CONDEMNATION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.1&#160;&#160;&#160;&#160;&#160;Casualty</b>. If all or any part of the Property is damaged by fire or other casualty occurring after
    the Effective Date and prior to Closing, whether or not such damage affects a material part of such Property, then:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Notice</u>. Seller shall provide written
    notice thereof to Buyer within three (3) days of such fire or casualty. In addition, Seller shall promptly notify Buyer of the estimated cost to repair as determined by a licensed architect or general contractor selected by Seller and reasonably
    approved by Buyer (the &#8220;<b>Cost Estimator</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Assignment of Insurance; Repairs</u>. In the
    event Buyer elects not to terminate this Agreement (or fails to timely give Seller notice of a termination) pursuant <u>Section 10.1(c)</u> below, the parties shall consummate this transaction in accordance with this Agreement, without any abatement
    of the Purchase Price or any liability or obligation on the part of Seller by reason of said destruction or damage. In such event, Seller shall assign to Buyer any casualty insurance proceeds payable under Seller&#8217;s casualty insurance policies
    (including, without limitation, business interruption proceeds applicable to the period of time from and after the Closing Date), if any, in effect with respect to the Property on account of said physical damage or destruction, and Seller shall
    cooperate with Buyer with initiating and pursuing any such claim. In addition to assigning all rights under and proceeds payable under casualty insurance policies with respect to such damage and destruction, Seller shall also pay to Buyer an amount
    equal to any &#8220;deductible&#8221; under such policies. Other than remedying unsafe conditions at the Property, Seller shall not remedy or repair any damage or destruction on account of such fire or casualty without the consent of Buyer, which consent shall not
    be unreasonably withheld or delayed, and the amount spent by Seller to remedy or repair the condition consented to by Buyer shall be deducted from the insurance proceeds otherwise made available to Buyer. Notwithstanding the foregoing, should the
    casualty not have been repaired prior to Closing then any proceeds of insurance with respect to such casualty actually received by Seller shall be promptly given to Buyer.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">37</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Termination Right</u>. Following
    a material casualty event, Buyer shall have the right to terminate this Agreement by giving a written notice of termination to Seller within ten (10) Business Days after Buyer receives a written estimate of the casualty or the estimated time to repair
    and cost to repair and/or replace the damage caused by the casualty, obtained pursuant to <u>Section 10.2</u> below. In the event of any termination by Buyer pursuant to this <u>Section 10.1(c)(c)</u>, then the Deposit, shall be promptly returned to
    Buyer by Escrow Holder, and this Agreement shall be and become null and void, and neither Party shall have any further rights or obligations hereunder, except for the Surviving Obligations. As used in this <u>Section</u> 10.1, a &#8220;material casualty
    event&#8221; means a casualty resulting in a cost to repair that is in excess of three percent (3%) of the Purchase Price.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; If Buyer does not timely give Seller notice of a termination pursuant <u>Section 10.1(c)</u>, then Buyer
    shall be deemed to have waived its right contained in <u>Section 10.1(c)(i)</u> to terminate this Agreement, and Buyer&#8217;s obligations under this Agreement shall remain in effect notwithstanding such casualty.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.2&#160;&#160;&#160;&#160;&#160;Time for Repair</b>. The estimated cost to repair and/or restore and the estimated time to complete such
    repairs contemplated in <u>Section </u>10.1 shall be established by estimates obtained by independent contractors retained by Seller, subject to the reasonable approval of Buyer. The Closing Date may be extended up to a maximum extension of thirty
    (30) calendar days as reasonably required to obtain such estimates and give the notices required under this Article X, and up to an additional sixty (60) days to determine the availability and amount of insurance proceeds available for such repairs.
    Seller and Buyer shall cooperate and exercise due diligence to obtain damage estimation and insurance proceeds.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 10.3&#160;&#160;&#160;&#160; Condemnation</b>. If, prior to Closing, any part of the Property is taken or if Seller shall receive
    notice from any Governmental Entity having eminent domain power over all or any part of the Property of its intention to take, by eminent domain proceeding, any material part of the Property (a &#8220;<b>Taking</b>&#8221;), then Buyer shall have the option,
    exercisable within twenty (20) days after receipt of written notice of such Taking, (and if necessary, Closing Date shall be extended to give the full period to make such election) time being of the essence, to terminate this Agreement by delivering
    notice thereof to Seller (a copy of such notice of termination shall be given to Escrow Holder), whereupon the Deposit shall be promptly returned to Buyer by Escrow Holder and this Agreement shall be deemed canceled and of no further force or effect,
    and neither Party shall have any further rights or liabilities against or to the other except for the Surviving Obligations. If a Taking shall occur and Buyer shall fail to terminate this Agreement in a timely fashion, then Buyer and Seller shall
    consummate this transaction in accordance with this Agreement, without any abatement of the Purchase Price or any liability or obligation on the part of Seller by reason of such Taking; provided, however, Seller shall (i) assign and remit to Buyer the
    full amount of any award or other proceeds of such Taking which may have been collected by Seller as a result of such Taking, or (ii) if no award or other proceeds shall have been collected, deliver to Buyer an assignment of Seller&#8217;s right to any such
    award or other proceeds which may be payable to Seller as a result of such Taking.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">38</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE XI <br>
    MISCELLANEOUS</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.1 &#160;&#160;&#160;&#160;&#160;Amendment and Modification</b>. Subject to applicable law, this Agreement may be amended, modified, or
    supplemented only by a written agreement signed by the party against whom enforcement is sought.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.2 &#160;&#160;&#160;&#160;&#160;Notices</b>. All notices required or permitted hereunder shall be in writing and shall be served on the
    parties at the following address(es):</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 24%; font-size: 10pt; text-align: right"><font style="font-size: 10pt">If to Seller:</font></td>
        <td style="width: 76%">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Ionis Pharmaceuticals, Inc.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">2855 Gazelle Ct.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attention: General Counsel</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right"><font style="font-size: 10pt">with a copy to:</font></td>
        <td>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Cooley LLP&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">4401 Eastgate Mall</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">San Diego, CA 92121</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attention: David Crawford</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right"><font style="font-size: 10pt">If to Buyer:</font></td>
        <td>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">c/o Oxford Properties Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Boston, MA 02110&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attn: Kristen Binck&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Email: [***]&#160;</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right"><font style="font-size: 10pt">With a copy to:</font></td>
        <td>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">c/o Oxford Properties Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">450 Park Avenue, 9<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">New York, NY 10022&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attn: Legal Department&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Email: [***]&#160;</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; text-align: right"><font style="font-size: 10pt">With a copy to:</font></td>
        <td>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">DLA Piper LLP (US)&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">33 Arch Street, 26<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Boston, MA 02110&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attn: John L. Sullivan, Esq.&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Email: [***]&#160;</p>
        </td>
      </tr>

  </table>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">39</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0; margin-bottom: 0"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 24%">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: right">If to Escrow</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: right">Holder:</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: right">&#160;</p>
        </td>
        <td style="width: 76%">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">First American Title Insurance Company</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">4380 La Jolla Drive&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Suite 110&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">San Diego, CA 92122&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Attn: [***]&#160;</p>
        </td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Any such notices may be sent by (a) certified mail, return receipt requested, in which case notice shall be deemed delivered upon actual or
    attempted but refused delivery, (b) a nationally recognized overnight courier, in which case notice shall be deemed delivered upon actual or attempted but refused delivery, (c) personal delivery, in which case notice shall be deemed delivered upon
    actual or attempted but refused delivery, or (d) Email transmission. The above addresses and Email addresses may be changed by written notice to the other party; provided that no notice of a change of address or Email address shall be effective until
    actual receipt of such notice.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.3&#160;&#160;&#160;&#160;&#160;Assignment</b>. Buyer shall not have the right to assign this Agreement, without the prior written
    consent of Seller, in its sole and absolute discretion. Notwithstanding the foregoing, Buyer may assign its interests herein (in whole or in part) to an Affiliate upon written notice to Seller (delivered, via email transmission, at least five (5)
    Business Days prior to the scheduled Closing Date), and assumption by such assignee of Buyer&#8217;s obligations hereunder, provided that such assignment will not relieve the original Buyer of its obligations hereunder until the Closing. This Agreement will
    be binding upon and inure to the benefit of Seller and Buyer and their respective successors and permitted assigns, and no other party will be conferred any rights by virtue of this Agreement or be entitled to enforce any of the provisions hereof.
    Whenever a reference is made in this Agreement to Seller or Buyer, such reference will include the successors and permitted assigns of such party under this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">Section 11.4&#160;&#160;&#160; Governing Law and Consent to Jurisdiction<font style="font-weight: normal">.</font> THIS AGREEMENT
    SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF CALIFORNIA, WITHOUT REGARD TO ANY OTHERWISE APPLICABLE PRINCIPLES OF CONFLICTS OF LAWS. ANY ACTION ARISING OUT OF THIS AGREEMENT MUST BE COMMENCED BY BUYER OR SELLER IN
    THE STATE COURTS OF THE STATE OF CALIFORNIA OR IN U.S. FEDERAL COURTS HAVING JURISDICTION OVER THE STATE OF CALIFORNIA AND EACH PARTY HEREBY CONSENTS TO THE JURISDICTION OF THE ABOVE COURTS IN ANY SUCH ACTION AND TO THE LAYING OF VENUE IN THE STATE OF
    CALIFORNIA<font style="font-weight: normal">.</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.5&#160;&#160;&#160;&#160;Counterparts; Electronic Signatures</b>. This Agreement may be executed in counterparts, each of which
    shall be deemed an original, but such counterparts, when taken together, shall constitute one agreement. This Agreement may be executed by a Party&#8217;s signature transmitted by email, and copies of this Agreement executed and delivered by means of emailed
    signatures shall have the same force and effect as copies hereof executed and delivered with original signatures. All parties hereto may rely upon emailed signatures (including signatures in Portable Document Format) as if such signatures were
    originals. All parties hereto agree that an emailed signature page may be introduced into evidence in any proceeding arising out of or related to this Agreement as if it were an original signature page.&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">40</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.6&#160;&#160;&#160;&#160; Entire Agreement</b>. This Agreement and any other document (including, without limitation,
    non-disclosure agreements executed by Buyer and/or its Affiliates, investors, and other related parties with respect to the transactions contemplated by this Agreement) to be furnished pursuant to the provisions hereof embody the entire agreement and
    understanding of the parties hereto as to the subject matter contained herein. There are no restrictions, promises, representations, warranties, covenants, or undertakings other than those expressly set forth or referred to in such documents. This
    Agreement and such documents (including, without limitation, non-disclosure agreements executed by Buyer and/or its Affiliates, investors, and other related parties with respect to the transactions contemplated by this Agreement) supersede all prior
    agreements and understandings among the parties with respect to the subject matter hereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.7&#160;&#160;&#160; Severability</b>. Any term or provision of this Agreement that is invalid or unenforceable in any
    jurisdiction will, as to such jurisdiction, be ineffective to the extent of such invalidity or unenforceability without rendering invalid or unenforceable the remaining terms and provisions of this Agreement or affecting the validity or enforceability
    of any of the terms or provisions of this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.8&#160;&#160;&#160; Attorney Fees</b>. If any action is brought by any party to this Agreement to enforce or interpret its
    terms or provisions, the prevailing party (whether by final judgment or out of court settlement) will be entitled to reasonable out of pocket third-party attorney fees and costs and expenses of suit incurred in connection with such action prior to and
    at trial and on any appeal therefrom. Any judgment or order entered in any final judgment shall contain a specific provision providing for the recovery of all costs and expenses of suit, including reasonable out of pocket third-party attorneys&#8217; fees
    (collectively &#8220;<b>Costs</b>&#8221;) incurred in enforcing, perfecting and executing such judgment. For the purposes of this paragraph, Costs shall include, without limitation, reasonable out of pocket third-party attorneys&#8217; fees, costs and expenses incurred
    in (i) post-judgment motions, (ii) contempt proceeding, (iii) garnishment, levy, and debtor and third party examination, (iv) discovery, and (v) bankruptcy litigation.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.9&#160;&#160;&#160;&#160; Payment of Fees and Expenses</b>. Each party to this Agreement will be responsible for, and will pay,
    all of its own fees and expenses, including those of its counsel and accountants, incurred in the negotiation, preparation, and consummation of this Agreement and the transaction contemplated hereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.10&#160;&#160; No Joint Venture</b>. Nothing set forth in this Agreement shall be construed to create a joint venture
    between Buyer and Seller.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">41</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.11 <u>JUDICIAL REFERENCE</u></b>. IT IS THE DESIRE AND INTENTION OF THE PARTIES TO AGREE UPON A MECHANISM AND
    PROCEDURE UNDER WHICH CONTROVERSIES AND DISPUTES ARISING OUT OF THE AGREEMENT, AS AMENDED, OR RELATED TO THE PROPERTY WILL BE RESOLVED IN A PROMPT AND EXPEDITIOUS MANNER. ACCORDINGLY, ANY ACTION, PROCEEDING OR COUNTERCLAIM BROUGHT BY EITHER PARTY
    HERETO AGAINST THE OTHER (AND/OR AGAINST ITS OFFICERS, DIRECTORS, EMPLOYEES, AGENTS OR SUBSIDIARIES OR AFFILIATED ENTITIES) ON ANY MATTERS WHATSOEVER ARISING OUT OF OR IN ANY WAY CONNECTED WITH THIS AGREEMENT, AS AMENDED, ANY CLAIM OF INJURY OR DAMAGE,
    WHETHER SOUNDING IN CONTRACT, TORT, OR OTHERWISE, SHALL BE HEARD AND RESOLVED BY A REFEREE UNDER THE PROVISIONS OF THE CALIFORNIA CODE OF CIVIL PROCEDURE, SECTIONS 638 &#8212; 645.1, INCLUSIVE (AS SAME MAY BE AMENDED, OR ANY SUCCESSOR STATUTE(S) THERETO)
    (THE &#8220;<b>REFEREE SECTIONS</b>&#8221;). ANY FEE TO INITIATE THE JUDICIAL REFERENCE PROCEEDINGS AND ALL FEES CHARGED AND COSTS INCURRED BY THE REFEREE SHALL BE PAID BY THE PARTY INITIATING SUCH PROCEDURE (EXCEPT THAT IF A REPORTER IS REQUESTED BY EITHER PARTY,
    THEN A REPORTER SHALL BE PRESENT AT ALL PROCEEDINGS WHERE REQUESTED AND THE FEES OF SUCH REPORTER &#8211; EXCEPT FOR COPIES ORDERED BY THE OTHER PARTIES &#8211; SHALL BE BORNE BY THE PARTY REQUESTING THE REPORTER); PROVIDED HOWEVER, THAT ALLOCATION OF THE COSTS
    AND FEES, INCLUDING ANY INITIATION FEE, OF SUCH PROCEEDING SHALL BE ULTIMATELY DETERMINED IN ACCORDANCE WITH THIS SECTION. THE VENUE OF THE PROCEEDINGS SHALL BE IN THE COUNTY IN WHICH THE PROPERTY IS LOCATED. WITHIN TEN (10) DAYS OF RECEIPT BY ANY
    PARTY OF A WRITTEN REQUEST TO RESOLVE ANY DISPUTE OR CONTROVERSY PURSUANT TO THIS <u>SECTION </u>13, THE PARTIES SHALL AGREE UPON A SINGLE REFEREE WHO SHALL TRY ALL ISSUES, WHETHER OF FACT OR LAW, AND REPORT A FINDING AND JUDGMENT ON SUCH ISSUES AS
    REQUIRED BY THE REFEREE SECTIONS. IF THE PARTIES ARE UNABLE TO AGREE UPON A REFEREE WITHIN SUCH TEN (10) DAY PERIOD, THEN ANY PARTY MAY THEREAFTER FILE A LAWSUIT IN THE COUNTY IN WHICH THE PROPERTY IS LOCATED FOR THE PURPOSE OF APPOINTMENT OF A REFEREE
    UNDER THE REFEREE SECTIONS. IF THE REFEREE IS APPOINTED BY THE COURT, THE REFEREE SHALL BE A NEUTRAL AND IMPARTIAL RETIRED JUDGE WITH SUBSTANTIAL EXPERIENCE IN THE RELEVANT MATTERS TO BE DETERMINED, FROM JAMS, THE AMERICAN ARBITRATION ASSOCIATION OR
    SIMILAR MEDIATION/ARBITRATION ENTITY. THE PROPOSED REFEREE MAY BE CHALLENGED BY ANY PARTY FOR ANY OF THE GROUNDS LISTED IN THE REFEREE SECTIONS. THE REFEREE SHALL HAVE THE POWER TO DECIDE ALL ISSUES OF FACT AND LAW AND REPORT HIS OR HER DECISION ON
    SUCH ISSUES, AND TO ISSUE ALL RECOGNIZED REMEDIES AVAILABLE AT LAW OR IN EQUITY FOR ANY CAUSE OF ACTION THAT IS BEFORE THE REFEREE, INCLUDING AN AWARD OF ATTORNEYS&#8217; FEES AND COSTS IN ACCORDANCE WITH THIS AGREEMENT, AS AMENDED. THE REFEREE SHALL NOT,
    HOWEVER, HAVE THE POWER TO AWARD PUNITIVE DAMAGES, NOR ANY OTHER DAMAGES WHICH ARE NOT PERMITTED BY THE EXPRESS PROVISIONS OF THE AGREEMENT, AS AMENDED, AND THE PARTIES HEREBY WAIVE ANY RIGHT TO RECOVER ANY SUCH DAMAGES. THE PARTIES SHALL BE ENTITLED
    TO CONDUCT ALL DISCOVERY AS PROVIDED IN THE CALIFORNIA CODE OF CIVIL PROCEDURE, AND THE REFEREE SHALL OVERSEE DISCOVERY AND MAY ENFORCE ALL DISCOVERY ORDERS IN THE SAME MANNER AS ANY TRIAL COURT JUDGE, WITH RIGHTS TO REGULATE DISCOVERY AND TO ISSUE AND
    ENFORCE SUBPOENAS, PROTECTIVE ORDERS AND OTHER LIMITATIONS ON DISCOVERY AVAILABLE UNDER CALIFORNIA LAW. THE REFERENCE PROCEEDING SHALL BE CONDUCTED IN ACCORDANCE WITH CALIFORNIA LAW (INCLUDING THE RULES OF EVIDENCE), AND IN ALL REGARDS, THE REFEREE
    SHALL FOLLOW CALIFORNIA LAW APPLICABLE AT THE TIME OF THE REFERENCE PROCEEDING. THE PARTIES SHALL PROMPTLY AND DILIGENTLY COOPERATE WITH ONE ANOTHER AND THE REFEREE AND SHALL PERFORM SUCH ACTS AS MAY BE NECESSARY TO OBTAIN A PROMPT AND EXPEDITIOUS
    RESOLUTION OF THE DISPUTE OR CONTROVERSY IN ACCORDANCE WITH THE TERMS OF THIS SECTION. IN THIS REGARD, THE PARTIES AGREE THAT THE PARTIES AND THE REFEREE SHALL USE BEST EFFORTS TO ENSURE THAT (A) DISCOVERY BE CONDUCTED FOR A PERIOD NO LONGER THAN SIX
    (6) MONTHS FROM THE DATE THE REFEREE IS APPOINTED, EXCLUDING MOTIONS REGARDING DISCOVERY, AND (B) A TRIAL DATE BE SET WITHIN NINE (9) MONTHS OF THE DATE THE REFEREE IS APPOINTED. IN ACCORDANCE WITH <u>SECTION </u>644 OF THE CALIFORNIA CODE OF CIVIL
    PROCEDURE, THE DECISION OF THE REFEREE UPON THE WHOLE ISSUE MUST STAND AS THE DECISION OF THE COURT, AND UPON THE FILING OF THE STATEMENT OF DECISION WITH THE CLERK OF THE COURT, OR WITH THE JUDGE IF THERE IS NO CLERK, JUDGMENT MAY BE ENTERED THEREON
    IN THE SAME MANNER AS IF THE ACTION HAD BEEN TRIED BY THE COURT. ANY DECISION OF THE REFEREE AND/OR JUDGMENT OR OTHER ORDER ENTERED THEREON SHALL BE APPEALABLE TO THE SAME EXTENT AND IN THE SAME MANNER THAT SUCH DECISION, JUDGMENT, OR ORDER WOULD BE
    APPEALABLE IF RENDERED BY A JUDGE OF THE SUPERIOR COURT IN WHICH VENUE IS PROPER HEREUNDER. THE REFEREE SHALL IN HIS/HER STATEMENT OF DECISION SET FORTH HIS/HER FINDINGS OF FACT AND CONCLUSIONS OF LAW. THE PARTIES INTEND THIS GENERAL REFERENCE
    AGREEMENT TO BE SPECIFICALLY ENFORCEABLE IN ACCORDANCE WITH THE CODE OF CIVIL PROCEDURE. NOTHING IN THIS <u>SECTION </u>SHALL PREJUDICE THE RIGHT OF ANY PARTY TO OBTAIN PROVISIONAL RELIEF OR OTHER EQUITABLE REMEDIES FROM A COURT OF COMPETENT
    JURISDICTION AS SHALL OTHERWISE BE AVAILABLE UNDER THE CODE OF CIVIL PROCEDURE AND/OR APPLICABLE COURT RULES.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.12 &#160;&#160;Time of Essence</b>. Time is of the essence of this Agreement. If the deadline for performance of any act
    hereunder shall fall on a day that is not a Business Day, the deadline for such performance shall be deemed to be the next Business Day following such day.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.13 &#160;&#160;No Waiver</b>. No waiver of any of the provisions of this Agreement shall be deemed, or shall constitute,
    a waiver of any other provision, whether or not similar, nor shall any waiver constitute a continuing waiver, nor shall a waiver in any instance constitute a waiver in any subsequent instance. No waiver shall be binding unless executed in writing by
    the Party making the waiver.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.14&#160;&#160; Not an Offer</b>. The preparation or distribution of drafts hereof by one party to the other shall not be
    deemed to constitute an offer and this Agreement shall only become binding and enforceable upon execution hereof by both parties.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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    create any third party beneficiary.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><b>Section 11.16 &#160;&#160;Exculpation</b>. Except as expressly set forth in this Agreement, (a) Seller&#8217;s shareholders, partners,
    members, the partners or members of such partners or members, the shareholders of such partners or members, and the trustees, officers, directors, employees, agents and security holders of Seller and the partners or members of Seller assume no personal
    liability for any obligations entered into on behalf of Seller and its individual assets shall not be subject to any claims of any person relating to such obligations, (b) Buyer&#8217;s shareholders, partners, members, the partners or members of such
    partners or members, the shareholders of such partners or members, and the trustees, officers, directors, employees, agents and security holders of Buyer and the partners or members of Buyer assume no personal liability for any obligations entered into
    on behalf of Buyer and their individual assets shall not be subject to any claims of any person relating to such obligations. The foregoing shall govern any direct and indirect obligations of Seller under this Agreement. The provisions of this Section
    11.16 shall survive the Closing or any termination of this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><font style="font-weight: normal">[</font>Balance of Page Intentionally Left Blank; signatures follow<font style="font-weight: normal">]</font>&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; color: #212121">IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly executed as of the day and year first above written.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; color: #212121">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 50%"><b><u>SELLER</u>:</b></td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 50%"><font style="font-family: Times New Roman, Times, Serif; text-transform: uppercase"><b>IONIS PHARMAceuticals, Inc.</b></font><b>,</b></td>
      </tr>
      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
        <td style="text-align: justify">a Delaware corporation</td>
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  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 3%">By:</td>
        <td style="text-align: justify; width: 47%; border-bottom: Black 1pt solid">/s/Elizabeth L. Hougen</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 5%">Name:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">Elizabeth L. Hougen</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="width: 5%; text-align: left">Title:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">EVP &amp; CFO</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 50%"><b><u>BUYER</u></b>:</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 50%"><b>OXFORD I ASSET MANAGEMENT USA INC., </b><br>
          a Delaware corporation</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 3%">By:</td>
        <td style="text-align: justify; width: 47%; border-bottom: Black 1pt solid">/s/Brian Barriero</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 5%">Name:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">Brian Barriero</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: left; width: 5%">Title:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">Vice President, Operations</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
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        <td style="text-align: justify; width: 3%">By:</td>
        <td style="text-align: justify; width: 47%; border-bottom: Black 1pt solid">/s/Kristen E. Binck</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 5%">Name:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">Kristen E. Binck</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: left; width: 5%">Title:</td>
        <td style="text-align: justify; width: 45%; border-bottom: Black 1pt solid">Vice President</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.75in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center; color: #212121"><i>[Signature Page </i>- <i>Build to Suite -Purchase</i> &amp; <i>Sale Agreement, Lots 21</i> &amp; <i>22]</i>&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">45</font></div>
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  <!--PROfilePageNumberReset%Num%45%%%-->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">JOINDER BY ESCROW HOLDER:</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">The Escrow Holder is executing this Agreement to evidence its agreement to act as escrow agent in accordance with the terms
    and conditions of this Agreement, including, without limitation, <u>Section 3.4</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 50%"><b>FIRST AMERICAN TITLE INSURANCE COMPANY</b></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
        <td style="text-align: justify; width: 3%">By:</td>
        <td style="text-align: justify; border-bottom: Black 1pt solid; width: 47%">/s/Lynn Graham</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT A</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Description of Real Property</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">The real property in the City of Carlsbad, County of San Diego, State of California, described as follows:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">TRACT TWO:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">LOTS 21 AND 22 OF CARLSBAD TRACT NO. 97-13-03, CARLSBAD OAKS NORTH PHASE 3, IN THE CITY&#160;OF CARLSBAD, COUNTY OF SAN DIEGO, STATE OF CALIFORNIA, ACCORDING TO MAP
    THEREOF NO.&#160; 16145, FILED IN THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY, OCTOBER 13, 2016&#160; AS DOCUMENT NO. 2016-7000438 OF OFFICIAL RECORDS.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;"><b><u>EXHIBIT B</u></b></p>
  <p style="font: 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;">&#160;</p>
  <p style="font: bold 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;"><u>List of Due Diligence Items</u></p>
  <p style="font: bold 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;">&#160;</p>
  <p style="font: 10pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;">[***]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
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  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT C</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Disclosure Items</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">Any item disclosed in any particular part of this <b><u>Exhibit C</u></b> will be deemed to be disclosed with respect to
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">This <b><u>Exhibit C</u></b> and the information and disclosures contained in this <b><u>Exhibit C</u></b> are intended
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT D</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Preliminary Title Report</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">[To be attached]</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"></p>
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        -1-</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">None.&#160;</p>
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        -1-</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Form of Deed</u></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="text-align: justify; padding-left: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="text-align: justify; border-left: Black 1pt solid"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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        <td style="text-align: justify; padding-left: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">[_________________________]</font></td>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="text-align: justify; padding-left: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">[_________________________]</font></td>
        <td style="text-align: justify; border-left: Black 1pt solid"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="text-align: justify; border-bottom: Black 1pt solid; padding-left: 10pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
        <td style="text-align: justify; border-left: Black 1pt solid; border-bottom: Black 1pt solid"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">APN:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Documentary transfer tax is $</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">GRANT DEED</p>
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      <tr style="vertical-align: top; text-align: justify">
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 50%"></td>
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  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

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        <td style="width: 3%">&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
        <td>&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><u>CALIFORNIA ALL-PURPOSE ACKNOWLEDGEMENT CIVIL CODE &#167;1189</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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        <td style="text-align: justify; border: Black 1pt solid; padding: 1pt 5pt 3pt">A notary public or other officer completing this certificate verifies only the identity of the individual who signed the document to which this certificate is attached,
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left">State of California &#160;&#160;&#160;&#160;&#160;}&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;}&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left">County of San Diego&#160;}</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: right">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">On __________________, before me, ________________________________, personally appeared _______________________________________<u>,</u> who
    proved to me on the basis of satisfactory evidence to be the person whose name is subscribed to the within instrument and acknowledged to me that he executed the same in his authorized capacity and that by his signature on the instrument the person, or
    the entity upon behalf of which the person acted, executed the instrument.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">I certify under PENALTY OF PERJURY under the laws of the State of California that the foregoing paragraph is true and correct.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">WITNESS my hand and official seal.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">(Notary Seal)</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Signature of Notary Public&#160;</p>
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  <p style="font: 8pt Times New Roman,Times,serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center;">EXHIBIT F</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">EXHIBIT A<br>
    LEGAL DESCRIPTION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">The real property in the City of Carlsbad, County of San Diego, State of California, described as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">TRACT TWO:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">LOTS 21 AND 22 OF CARLSBAD TRACT NO. 97-13-03, CARLSBAD OAKS NORTH PHASE 3, IN THE CITY OF CARLSBAD, COUNTY OF SAN DIEGO, STATE OF CALIFORNIA,
    ACCORDING TO MAP THEREOF NO. 16145, FILED IN THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY, OCTOBER 13, 2016 AS DOCUMENT NO. 2016-7000438 OF OFFICIAL RECORDS.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">APN : 209-120-23-00 (Affects Lot 21 of Tract Two)</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">EXHIBIT B</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">Permitted Exceptions</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">1.</td>
        <td style="text-align: justify">General and special taxes and assessments for the fiscal year 2022-2023, a lien not yet due or payable.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">Affects APNs: 209-120-23-00 and 209-120-24-00</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">2.</td>
        <td style="text-align: justify">The lien of special tax for the following community facilities district, which tax is collected with the county taxes, a lien not yet due and payable.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">District: Carlsbad CFD #3 IMP 2</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
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        <td style="width: 0.25in"></td>
        <td style="width: 18pt">3.</td>
        <td style="text-align: justify">The lien of supplemental taxes, if any, assessed pursuant to Chapter 3.5 commencing with Section 75 of the California Revenue and Taxation Code, resulting from changes in ownership or completion of construction on or
          after the date of the policy.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">4.</td>
        <td style="text-align: justify">The terms and provisions contained in the document entitled &#8220;Notice of Restriction on Real Property&#8221; recorded November 9, 2004 as Instrument No. 2004-1066056 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">5.</td>
        <td style="text-align: justify">The terms and provisions contained in the document entitled &#8220;Notice and Waiver Concerning Proximity of the Planned or Existing Palomar Airport Road and Melrose Drive Transportation Corridors Case No: CT 97-13&#8221;
          recorded November 9, 2004 as Instrument No. 2004-1066058 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">6.</td>
        <td style="text-align: justify">The terms and provision contained in the document entitled &#8220;Hold Harmless Agreement Drainage&#8221; recorded December 15, 2004 as Instrument No. 2004-1180067 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">7.</td>
        <td style="text-align: justify">The terms and provision contained in the document entitled &#8220;Hold Harmless Agreement Geological Failure&#8221; recorded December 15, 2004 as Instrument No. 2004-1180068 of Official Records.</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">8.</td>
        <td style="text-align: justify">Covenants, conditions, restrictions, easements, assessments, liens, charges, terms and provision in the document entitled &#8220;Declaration of Covenants, Conditions and Restrictions for Carlsbad Oaks North Business Park&#8221;
          recorded February 5, 2007 as Instrument No. 2007-0081082 of Official Records, which provide that a violation thereof shall not defeat or render invalid the lien of any first mortgage or deed of trust made in good faith and for value, but deleting
          any covenant, condition or restriction indicating a preference, limitation or discrimination based on race, color, religion, sex, handicap, familial status, national origin, sexual orientation, marital status, ancestry, source of income or
          disability, to the extent such covenants, conditions or restrictions violate Title 42, Section<u>&#160;</u>3604&#169;, or the United States Codes. Lawful restrictions under state and federal law on the age of occupants in senior housing or housing for
          older persons shall not be construed as restrictions based on familial status.</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in">Documents declaring modification thereof in document entitled &#8220;First Amendment to Declaration of Covenants, Conditions, and Restrictions for
    Carlsbad Oaks North Business Park&#8221;, recorded March 20, 2013 as Instrument No. 2013-0175873 of Official Records.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify">A declaration of annexation entitled &#8220;Declaration of Annexation to Declaration of Covenants, Conditions and Restrictions for
    Carlsbad Oaks North Business Park&#8221;, recorded October 25, 2016 as Instrument No. 2016-0576403 of Official Records.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">9.</td>
        <td style="text-align: justify">The terms and provisions contained in the document entitled &#8220;Hold Harmless Agreement Drainage&#8221; recorded September 2, 2016 as Instrument No. 2016-0460153 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 18pt">10.</td>
        <td style="text-align: justify">The terms and provisions contained in the document entitled &#8220;Hold Harmless Agreement Geological Failure&#8221; recorded September 2, 2016 as Instrument No. 2016-0460154 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">11.</td>
        <td style="text-align: justify">Abutter&#8217;s rights of ingress and egress to or from Whiptail Loop except at access opening have been dedicated or relinquished on the map of Carlsbad Tract No. 97-13-03 of Tract Maps recorded as Map No. 16145.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 18pt">12.</td>
        <td style="text-align: justify">The terms, provisions and easement(s) contained in the document entitled &#8220;Easement and Maintenance Agreement&#8221; recorded October 01, 2018 as Instrument No. 2018-407532 of Official Records.</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><u>Form of First Right Agreement&#160;</u></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><u>FIRST RIGHT AGREEMENT</u></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify">THIS FIRST RIGHT AGREEMENT (this <b><i>&#8220;</i><u>Agreement</u><i>&#8221;</i></b>) is effective as of __________ __, 20___ (&#8220;<b><u>Effective






        Date</u></b>&#8221;), by and between IONIS PHARMACEUTICALS, INC., a Delaware corporation (&#8220;<b><u>Owner</u></b>&#8221;), and [OXFORD], a Delaware limited liability company (&#8220;<b><u>Offeree</u></b>&#8221;). Owner and Offeree are sometimes hereinafter individually or
    collectively called a &#8220;<b>Party</b>&#8221; or the &#8220;<b>Parties</b>&#8221;.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>RECITALS</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify">A.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Owner owns the real property and associated
    improvements thereon in Carlsbad, California, more particularly described on <u>Exhibit A</u> attached hereto (the &#8220;<b><u>Property</u></b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify">B.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Owner and Offeree had previously entered into a
    purchase and sale agreement with respect to the Property (the &#8220;<b><u>Prior PSA</u></b>&#8221;), and the transaction contemplated under such purchase and sale agreement did not close as contemplated therein. As a result thereof, the Parties have entered into
    this Agreement to provide Offeree with certain rights with respect to the Property if Owner desires to Transfer (as hereinafter defined) all or substantially all of the Property or any direct or indirect interest therein, subject to the terms,
    conditions and limitations set forth herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>AGREEMENT</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify">NOW, THEREFORE, in consideration of the foregoing recitals, which are hereby incorporated with the same force and effect as
    if contained in this Agreement below, and other valuable consideration, the receipt of which are hereby acknowledged, Owner hereby grants to Offeree the rights with respect to the Property as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"><b>Section 1.1.</b>&#160;&#160; The all cash gross purchase price, chosen by Owner in its sole and absolute discretion, at which
    Owner desires to offer the Property for sale or other transfer on a free and clear basis (the &#8220;<b><u>ROFO Price</u></b>&#8221;). A ROFO Notice shall constitute an irrevocable offer by the Owner to sell or otherwise transfer its entire interest in the
    Property to Offeree or its assignee for the ROFO Price, free and clear of all encumbrances. For the avoidance of doubt, the right of first offer described in this <u>Section 1</u> shall not apply to any Excluded Transfer. Within thirty (30) days after
    receiving the ROFO Notice (&#8220;<b><u>ROFO Expiration Date</u></b>&#8221;), Offeree shall send Owner written notice stating either (i) that Offeree waives its rights under this <u>Section 1</u> or (ii) Offeree accepts the ROFO Notice (the &#8220;<b><u>ROFO Acceptance
        Notice</u></b>&#8221;). If Offeree sends a ROFO Acceptance Notice, the parties shall use good faith efforts to negotiate the terms on which Offeree shall acquire the Property (or the direct or indirect interests therein), other than the purchase price,
    which shall be the ROFO Price, and shall enter into a purchase and sale agreement substantially similar to Prior PSA. If Offeree waives its rights with respect to the ROFO Notice or fails to provide a ROFO Acceptance Notice on or prior to the ROFO
    Expiration Date, or does not execute a purchase and sale agreement for the Property within sixty (60) days of its delivery of a ROFO Acceptance Notice, then Owner shall be free to Transfer (as hereinafter defined) the Property (or any interests
    therein) to any third party, subject to the terms of <u>Section 2</u> of this Agreement. <b><u>Grant of Right of First Refusal</u></b><u>. <b>Sale or Transfer of Property</b></u>. Offeree shall have a right of first refusal to purchase or otherwise
    acquire Owner&#8217;s interest in the Property (whether direct or indirect and whether by deed or ground lease or otherwise), subject to and in accordance with the terms and conditions set forth in this <u>Section 2</u> (the &#8220;<b><u>ROFR</u></b>&#8221;). For the
    avoidance of doubt, the ROFR and the provisions of this <u>Section 2</u> shall not apply to any Excluded Transfer.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"> <br>
  </p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"><b>Section 2.2.&#160;&#160; <u>Offer Notice</u></b>. Before Owner enters into any contract or consummates any transaction that
    would, whether in one transaction or a series of related transactions, result in the direct or indirect sale, transfer, or conveyance of the fee simple title in and to all or substantially all of the Property (or any parcel comprising the Property) or
    the legal or beneficial interest therein to a bona fide third party purchaser for value, whether by deed or ground lease or indirect entity transfer (each, a &#8220;<b><u>Transfer</u></b>&#8221;), Owner shall first afford Offeree the opportunity to purchase or
    ground lease, as applicable, the Property in accordance with the provisions of this <u>Section 2</u> by delivering a written offer notice thereof to Offeree (the &#8220;<b><u>Offer Notice</u></b>&#8221;) containing the following: (1) the cash purchase price (the
    &#8220;<b><u>Price</u></b>&#8221;) that Owner will accept for the Property, provided that (i) if the Price is in excess of the purchase price proposed to be paid by Offeree under the Prior PSA (the &#8220;<b><u>Prior Price</u></b>&#8221;), then the purchase price to be paid
    by Offeree shall be the Prior Price and (ii) if the Price is less than the Prior Price, then the purchase price to be paid by Offeree shall be the Price; (2) the amount of any earnest money deposit required to be deposited into escrow by Offeree; (3)
    the length of the contingency period at the expiration of which the earnest money deposit will become non-refundable (other than with respect to Owner defaults, failures of conditions precedent in favor of the Offeree and casualty or condemnation
    provisions); and (4) the proposed outside closing date for the closing of the subject transaction (collectively (1) &#8211; (4), the &#8220;<b>Material Terms</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"><b>Section 2.3.&#160;&#160; <u>Acceptance Notice</u></b>. Within ten (10) business days after receiving the Offer Notice (&#8220;<b>Expiration






      Date</b>&#8221;), Offeree shall send Owner and Escrow Agent (as defined in <u>Section 7</u> below) written notice stating either (i) that Offeree waives its rights under this <u>Section 2</u> (subject to <u>Section 2.4</u> below) or (ii) Offeree accepts
    the Offer Notice (the &#8220;<b>Acceptance Notice</b>&#8221;). If Offeree sends an Acceptance Notice, then the parties will commence to negotiate the terms on which Offeree would acquire the Property or the interests therein, other than the Material Terms included
    in the Offer Price, and shall enter into a purchase and sale agreement substantially similar to Prior PSA.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"><b>Section 2.4.&#160;&#160; <u>Re-Offer Procedure</u></b>. If Offeree waives its rights with respect to the Offer Notice or fails to
    provide an Acceptance Notice on or prior to the Expiration Date or does not execute a purchase and sale agreement for the Property within sixty (60) days of its delivery of an Acceptance Notice, then the Offer Notice shall be deemed to have no further
    force or effect and Owner shall be free to Transfer the Property (or the interests therein) to any third party, <i>provided </i>that, if (a) Owner reduces the gross Price to an amount less than the gross Price set forth in the Offer Notice or (b)
    Owner does not enter into a purchase and sale agreement for the Property on or before the date that is three (3) months after the Expiration Date (or fails to close on such sale of the Property within three (3) months after the end of such three (3)
    month period), then Owner shall recommence the procedures under <u>Section 2.2</u> prior to consummating a Transfer of its interest in the Property.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"> <br>
  </p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1.25in"> </p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"><b>Section 3.&#160;&#160;&#160;&#160;&#160;&#160;<u>Termination of ROFO and ROFR</u></b>. The term of this Agreement shall commence as of the Effective
    Date and shall automatically terminate on the earlier of (a) the Transfer of the Property (or any indirect interest therein) to Offeree or its affiliate, (b) the Transfer of the Property (or any indirect interest therein) to a third party following
    Owner&#8217;s compliance with the terms of this Agreement, or (c) the date that is five (5) years after the Effective Date, at which time the Parties shall execute (and notarize, if applicable) and deliver any and all documents reasonably requested by Escrow
    Agent at such time to remove this Agreement from the Official Records.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"><b>Section 4.&#160;&#160;&#160;&#160;&#160;&#160; <u>Excluded Transfers</u></b>. Notwithstanding anything to the contrary in this Agreement, this
    Agreement shall not apply to any of the following (each, an &#8220;<b>Excluded Transfer</b>&#8221;): (i) the granting or foreclosure of any mortgage on or other security interest in the Property (or collateral assignment of rights in respect of the Property), any
    foreclosure sale pursuant thereto, any deed in lieu of such foreclosure (whether to mortgagee or its designee), or any transfers by such mortgagees, purchasers at foreclosure or deed in lieu transaction, or their successors or assigns (and in
    connection with any such transfer, Offeree shall no longer have any right of first offer or ROFR) with respect to the Property, this Agreement shall terminate and the Property shall be conclusively released from the rights of Offeree under this
    Agreement); (ii) any utility, construction and other easements and encumbrances of title of any type; (iii) any transfer or sale of the Property to an entity that is wholly-owned and controlled by Owner, or any transfer or sale of publicly-traded
    shares in Owner (provided that this Agreement shall survive any transfer or sale of publicly-traded shares in Owner), or a merger or acquisition of Owner as a going concern (and not primarily for purposes of acquiring the Property); (iv) entering into
    the Buyer-Seller Lease or any amendments thereto; or (v) any condemnation or taking or agreement in lieu thereof.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"><b>Section 5.&#160;&#160;&#160;&#160;&#160; <u>Assignment</u></b>. Offeree may assign its rights and duties hereunder upon written notice, but
    without the consent of Owner, to any entity that is controlled or owned by, controls or owns or is under common control or ownership with Offeree. Owner may not assign its rights and duties hereunder without Offeree&#8217;s consent, other than to any entity
    that is controlled or owned by, controls or owns or is under common control or ownership with Owner. <b><u>Default; Remedies</u></b>. If any Party defaults hereunder, the non-defaulting Party may pursue any and all rights and remedies that may be
    available at law or in equity. In the event of any action or proceeding at law or in equity between Owner and Offeree to enforce any provision of this Agreement or to protect or establish any right or remedy of any Party hereunder, the unsuccessful
    Party to such litigation shall pay the prevailing Party all costs and expenses, including reasonable attorneys&#8217; fees incurred therein by such prevailing Party.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"> <br>
  </p>
  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"> </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.85in; margin-bottom: 0pt; text-align: justify"><b>Section 7.&#160;&#160;&#160;&#160;&#160; <u>Notices</u></b>. Any notice which a Party is required or may desire to give another Party shall be
    in writing and may be delivered (1) by hand delivery, (2) by United States registered or certified mail, postage prepaid, (3) by Federal Express or other reputable courier service regularly providing evidence of delivery (with charges paid by the Party
    sending the notice), or (4) by electronic mail, provided that (i) in the event of delivery by the methods described in clauses (1), (2) or (3) above, the Party shall also deliver such notice by electronic mail, and (ii) in the event of delivery by the
    method in clause (4) above, such electronic mail shall be immediately followed by delivery of such notice pursuant to clause (1), (2) or (3) above. Any such notice to a Party shall be addressed at the address set forth below (subject to the right of a
    Party to designate a different address for itself by notice similarly given). Service of any such notice or other communications so made shall be deemed effective on the day of actual delivery (whether accepted or refused) unless such party receives a
    &#8220;bounce-back&#8221; electronic mail response, as shown by the addressee&#8217;s return receipt if by certified mail, and as confirmed by the courier service if by courier; provided, however, that if such actual delivery occurs after 6:00 p.m. (local time where
    received) or on a non-business day, then such notice or demand so made shall be deemed effective on the first business day after the day of actual delivery. Notices may be delivered by counsel to the Parties hereto with the same force and effect. The
    Parties&#8217; addresses for notices are as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 80%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-left: 0.85in">

      <tr style="vertical-align: top">
        <td style="width: 20%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>If to Owner:</u></font></td>
        <td style="width: 60%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Ionis Pharmaceuticals, Inc.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2855 Gazelle Ct.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Carlsbad, California 92008</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attention: General Counsel</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">With a copy to:</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Cooley LLP</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4401 Eastgate Mall</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">San Diego, CA 92121</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attention: David Crawford</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>If to Offeree:</u></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">c/o Oxford Properties Group</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Boston, MA 02110</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attn: Kristen Binck</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">With a copy to:</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">c/o Oxford Properties Group</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">450 Park Avenue, 9<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">New York, NY 10022</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attn: Legal Department</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">With a copy to:</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">DLA Piper LLP (US)</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">33 Arch Street, 26<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Boston, MA 02110</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attn: John L. Sullivan, Esq.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>If to Escrow Agent:</u></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">First American Title Insurance Company (<b>&#8220;<u>Escrow Agent</u>&#8221;</b>)</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4380 La Jolla Drive, Suite 110</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">San Diego, CA 92122</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attn: Lynn Graham</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td>
          <div><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Email: [***]</font></div>
        </td>
      </tr>

  </table>
  <div><br>
  </div>
  <div>
    <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
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  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.85in">IN WITNESS WHEREOF, the undersigned have executed this Agreement as of the date first above written.</p>
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        <td style="width: 50%"><font style="font-size: 10pt"><b>OWNER</b>:</font></td>
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        <td> a Delaware corporation </td>
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    <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>LEGAL DESCRIPTION</u></p>
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    <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT G-1</div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Form of Memorandum of First Right Agreement</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">RECORDING REQUESTED BY</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">DLA Piper LLP&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attention: John L. Sullivan</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>MEMORANDUM OF FIRST RIGHT AGREEMENT</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">THIS MEMORANDUM OF FIRST RIGHT AGREEMENT (this &#8220;<b>Memorandum</b>&#8221;) is made as of _____________, 202__, by and between <b>IONIS






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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>Form of Assignment and Assumption Agreement</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT I</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><u>Form of Seller&#8217;s Certificate</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Reference is hereby made to that certain Purchase and Sale Agreement dated as of ___________, 2022 (the &#8220;<b>Purchase Agreement</b>&#8221;), by and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Seller hereby certifies to Buyer that each of the representations and warranties of Seller set forth in the Purchase Agreement are, as of the
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        <td style="width: 50%">&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"></p>
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        <td style="width: 50%">&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
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      <tr style="vertical-align: top">
        <td style="width: 50%">&#160;</td>
        <td style="width: 5%">Title:</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
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        -1-</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT J</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><u>Form of Buyer&#8217;s Certificate</u></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Reference is hereby made to that certain Purchase and Sale Agreement dated as of ___________, 2022 (the &#8220;<b>Purchase Agreement</b>&#8221;), by and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Buyer hereby certifies to Seller that each of the representations and warranties of Buyer set forth in the Purchase Agreement are, as of the
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Dated as of this ___ day of ___________, 2022.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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      <tr style="vertical-align: top; text-align: justify">
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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      <tr style="vertical-align: top; text-align: justify">
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        <td style="text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-style: normal">[____________________________________]</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 50%">&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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      <tr style="vertical-align: top">
        <td style="width: 50%">&#160;</td>
        <td style="width: 5%">Name:</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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      <tr style="vertical-align: top">
        <td style="width: 50%">&#160;</td>
        <td style="width: 5%">Title:</td>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: left"></p>
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        -1-</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>EXHIBIT K</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b><u>Form of Owner&#8217;s Affidavit</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">FIRST AMERICAN TITLE INSURANCE COMPANY</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>STATEMENT REQUIRED FOR THE ISSUANCE OF ALTA OWNERS AND/OR LOAN POLICIES</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Commitment No. ________________</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Date: ______________</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">To the best knowledge and belief of the undersigned, the following is hereby certified with respect to the land described in the above commitment:</p>
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        <td style="width: 0.25in"></td>
        <td style="width: 0.25in">1.</td>
        <td style="text-align: justify">That, except as noted at the end of this paragraph, within the last six (6) months (a) no labor, service or materials have been furnished to improve the land, or to rehabilitate, repair, refurbish, or remodel the
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          machinery, apparatus or equipment which are to be completed subsequent to the date hereof; (d) nor have any notices of lien been received, except the following, if any:</td>
      </tr>
      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: justify">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
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        <td style="width: 0.25in"></td>
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        <td style="text-align: justify">That there are no unrecorded contracts or options to purchase the land, except the following, if any:</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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        <td style="width: 0.25in"></td>
        <td style="width: 0.25in">3.</td>
        <td style="text-align: justify">That there are no unrecorded leases, easements or other servitudes to which the land or building, or portions thereof, are subject, except the following, if
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in">4.</td>
        <td style="text-align: justify">That there are no rights of first refusal or options to purchase all or any part of the Property except:________________________________________________</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in"></td>
        <td style="width: 0.25in">5.</td>
        <td style="text-align: justify">That there are no unpaid real estate taxes or assessments except as shown on the current tax roll. That the undersigned has not received any supplemental tax bill which is unpaid.</td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in"></td>
        <td style="width: 0.25in">6.</td>
        <td style="text-align: justify">That the undersigned is authorized to execute this affidavit, has the ability to execute all instruments necessary to mortgage or convey the Land pursuant to authority, and that the owner was properly created and is
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in">7.</td>
        <td style="text-align: justify">That the undersigned has not received any written notice of violation of any covenants, conditions or restrictions, if any, affecting the Land.</td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in">8.</td>
        <td style="text-align: justify">In order to induce First American Title Insurance Company (the &#8220;Company&#8221;) to issue its policy(ies) of title insurance with full knowledge that the Company will rely upon the accuracy of same, the undersigned hereby
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      </tr>

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        -1-</font></div>
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        <td style="text-align: justify">The undersigned does hereby agree to indemnify and hold the Company harmless of and from any and all loss, cost, damage and expense of every kind, including attorneys&#8217; fees, which the Company shall or may suffer or
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
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        <td style="text-align: justify">The undersigned does hereby agree to indemnify and hold the Company harmless during the gap period between the last title examination of the Land that was conducted by, for and/or on behalf of the Company, and the
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red">&#160;</p>
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        <td style="width: 1.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">State of California</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">On &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;, before me, _ &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;, personally appeared
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">WITNESS my hand and official seal.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">(Notary Seal)</p>
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  <p style="margin-top: 0pt; font: 10pt Times New Roman, Times, Serif; margin-bottom: 0pt; color: Red"></p>
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        -3-</font></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">Non-Foreign Status Affidavit</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">Section 1445 of the Internal Revenue Code of 1986, as amended (the &#8220;<b><i>Code</i></b>&#8221;), provides that a transferee of a United States real
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    transferor of the property and not the disregarded entity. To inform the transferee that withholding of tax is not required upon the disposition of a United States real property interest by _________________________ (&#8220;<b><i>Transferor</i></b>&#8221;), which
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Transferor is not a non resident alien individual foreign corporation,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"> 4. &#160;&#160;&#160;&#160;&#160;&#160;&#160;Transferor&#8217;s office address is <u>______________________________</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">[signature on following page]&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"> <br>
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  <div style="text-align: center; color: rgb(0, 0, 0); font-family: 'Times New Roman',Times,serif; font-size: 8pt;">EXHIBIT L</div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"> </p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

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        <td style="width: 60%"></td>
        <td style="text-align: justify; width: 40%; border-top: Black 1pt solid">a</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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      <tr style="vertical-align: top; text-align: justify">
        <td>&#160;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">IONIS PHARMACEUTICALS, INC.,&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>a Delaware corporation</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>AS TENANT</b>&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">BASIC LEASE INFORMATION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">For convenience of the parties, certain basic provisions of this Lease are set forth herein, and are, together with any Exhibits and Schedules,
    expressly incorporated into the Lease. The provisions set forth herein are subject to the remaining terms and conditions of this Lease and are to be interpreted in light of such remaining terms and conditions.</p>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 35%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>TERMS OF LEASE</b></font></td>
        <td style="width: 65%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>DESCRIPTION</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Commencement Date</b>&#8221;:</font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">The date that is the earlier of: (i) ten (10) months after the Delivery Date, as defined in the Work Letter, or (ii) the date Tenant begins
            operating in the Premises for business purposes.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Premises</b>&#8221;:</font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">That certain Land described on <u>Exhibit A</u> attached hereto and the Building and other improvements to be constructed thereon, located on Lots
            21 &amp; 22, Whiptail Loop W in Carlsbad, 92010 California consisting of approximately 164,833 gross square feet, and the appurtenances thereto, as defined and further described in the Work Letter. The square footage of the Premises set forth
            above is deemed conclusive and shall not be subject to remeasurement</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>&#8220;Companion Lease&#8221;:</b></font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">That certain lease to be executed between Landlord or its affiliate and Tenant pursuant to the PSA for certain real property located at 2850, 2855
            &amp; 2859 Gazelle Court, Carlsbad, 92010 California (the &#8220;<b>Companion Premises</b>&#8221;) and the buildings consisting of approximately 246,699 square feet and other improvements located thereon and appurtenances thereto, as described therein.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Term</b>&#8221;: (<u>Article 1</u>)</font></td>
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">The period commencing on the Commencement Date and ending on the Expiration Date.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>&#8220;Expiration Date</b>&#8221;</font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">The date that is one hundred eighty (180) months after the Commencement Date, together with any Extension Period as to which an Extension Option is
            exercised under Section 1.4.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt"><font style="font-size: 10pt">&#8220;<b>Escalation</b>&#8221;: (<u>Article 2</u>)</font></td>
        <td style="font-size: 10pt; text-align: justify"><font style="font-size: 10pt">The percentage of increase, if any, shown by the Consumer Price Index for All Urban Consumers U.S. City Average, All Items (base years 1982-1984 = 100) (&#8220;<b>Index</b>&#8221;),
            published by the United States Department of Labor, Bureau of Labor Statistics, for the month immediately preceding the Adjustment Date as compared with the Index for the month immediately preceding the Commencement Date (with respect to the
            first Adjustment Date), or the month immediately preceding the prior Adjustment Date (for all subsequent Adjustment Dates), but the percentage of increase shall not be less than 2.5% nor greater than 5.5%.</font></td>
      </tr>

  </table>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">1</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 35%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>TERMS OF LEASE</b></font></td>
        <td style="width: 65%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>DESCRIPTION</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Option to Renew</b>&#8221;: (<u>Article 1</u>)</font></td>
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">Tenant shall have two (2), five year (5) options at ninety-five percent (95%) of fair market rent.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Base Rent</b>&#8221;: (<u>Article 2</u>)</font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">For the period beginning on the Commencement Date until the first Adjustment Date, a fixed annual amount (payable in monthly installments)
            determined by multiplying six and thirty-five hundredths percent (6.35%) by the Construction Costs, as defined in the Work Letter, and thereafter the amount calculated pursuant to Section 2.1.3. A hypothetical example of the calculation of Base
            Rent is shown on Schedule 1, which shall be for illustrative purposes only and shall not be deemed a representation of the actual amounts or categories to be used in the calculation of Base Rent.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Net Lease</b>&#8221;: (<u>Article 2</u>)</font></td>
        <td style="font-size: 10pt; text-align: justify; padding-bottom: 10pt"><font style="font-size: 10pt">Landlord and Tenant acknowledge and agree that this is an &#8220;absolute net lease&#8221; and that Landlord shall receive the Base Rent during the Term, free
            from all charges, assessments, impositions, expenses and deductions of any and every kind or nature whatsoever relating to the Premises. Landlord shall have no obligations relating to the repair, maintenance or operation of the Premises, or any
            part thereof. Tenant shall be solely responsible for same.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Purchase Option</b>&#8221;: (Article 11)</font></td>
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">Tenant shall have a right of first offer to purchase the entire Premises.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt"><font style="font-size: 10pt">&#8220;<b>Security Deposit/Letter of Credit</b>&#8221;: (<u>Article 2</u>)</font></td>
        <td style="font-size: 10pt; text-align: justify"><font style="font-size: 10pt">Tenant shall provide a Letter of Credit equal to ten (10) months of the initial Base Rent, subject to adjustment as provided in Section 2.5.1.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt"><font style="font-size: 10pt">&#8220;<b>Permitted Use</b>&#8221;: (<u>Article 3</u>)</font></td>
        <td style="font-size: 10pt; text-align: justify"><font style="font-size: 10pt">Premises may be used solely for biotechnology and other life sciences uses, including research and development, laboratory, manufacturing, assembly, storage,
            warehousing, office and administrative uses, all of which must be ancillary to biotechnology and other life sciences uses and, in each such case, to the extent Tenant remains in compliance with current zoning for the Premises and all Applicable
            Laws.</font></td>
      </tr>

  </table>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font></div>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 35%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>TERMS OF LEASE</b></font></td>
        <td style="width: 65%; font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>DESCRIPTION</b></font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt"><b>&#8220;Work Letter&#8221;</b>: (Exhibit D)</font></td>
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">The &#8220;Work Letter&#8221; attached hereto as <u>Exhibit D</u>.</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Address of Tenant</b>&#8221;: (<u>Article 13</u>)</font></td>
        <td style="padding-bottom: 10pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Ionis Pharmaceuticals, Inc.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">2855 Gazelle Ct.&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attention: General Counsel</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Email: [***]</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">With a copy to:</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Cooley LLP&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">4401 Eastgate Mall&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">San Diego, CA 92121-1909&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attn: David L. Crawford, Esq.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Email: [***]</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="font-size: 10pt; padding-bottom: 10pt"><font style="font-size: 10pt">&#8220;<b>Address of Landlord</b>&#8221;: (<u>Article 13</u>)</font></td>
        <td style="padding-bottom: 10pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">c/o Oxford Property Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Boston, MA 02110&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">United States&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attn: Kristin Binck, Esq.,</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Vice President, Legal&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Email: [***]</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">With a copy to:</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">c/o Oxford Property Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">101 Second St, Suite 300</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">San Francisco, CA 94105</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attn: Abby Mondani</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">and</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">DLA Piper LLP (US)&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">33 Arch Street, 26<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Boston, MA 02110</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">United States&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Attn: John L. Sullivan, Esq.&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">Email: [***]</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">and all legal notices shall also be sent to:</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">[***]</p>
        </td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b><u>TABLE OF CONTENTS</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 50%">ARTICLE 1 LEASE OF PREMISES; TERM</td>
        <td style="width: 50%; text-align: right">1</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">1.1</td>
        <td style="text-align: justify; width: 84%">Lease </td>
        <td style="text-align: right; width: 5%">1</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">1.2</td>
        <td style="text-align: justify; width: 84%">As Is; No Representations </td>
        <td style="text-align: right; width: 5%">1</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">1.3</td>
        <td style="text-align: justify; width: 84%">Holdover </td>
        <td style="text-align: right; width: 5%">2</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">1.4</td>
        <td style="text-align: justify; width: 84%">Extension Option </td>
        <td style="text-align: right; width: 5%">2</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 50%">ARTICLE 2 RENT</td>
        <td style="width: 50%; text-align: right">4</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">2.1</td>
        <td style="text-align: justify; width: 84%">Base Rent and Additional Rent </td>
        <td style="text-align: right; width: 5%">4</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">2.2</td>
        <td style="text-align: justify; width: 84%">Expenses; Taxes; Insurance Expenses </td>
        <td style="text-align: right; width: 5%">6</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">2.3</td>
        <td style="text-align: justify; width: 84%">Net Lease </td>
        <td style="text-align: right; width: 5%">8</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">2.4</td>
        <td style="text-align: justify; width: 84%">Interest and Late Charge </td>
        <td style="text-align: right; width: 5%">9</td>
      </tr>

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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
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        <td style="text-align: right; width: 5%">9</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
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      <tr style="vertical-align: top">
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
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        <td style="text-align: right; width: 5%">13</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
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        <td style="text-align: justify; width: 84%">Hazardous Materials </td>
        <td style="text-align: right; width: 5%">13</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">3.4</td>
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        <td style="text-align: right; width: 5%">18</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
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        <td style="text-align: right; width: 5%">20</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
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        <td style="text-align: right; width: 5%"> 21</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">3.7</td>
        <td style="text-align: justify; width: 84%">LEED Standards </td>
        <td style="text-align: right; width: 5%">22</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 50%">ARTICLE 4 REPAIR AND MAINTENANCE; SERVICES</td>
        <td style="width: 50%; text-align: right">22</td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">4.1</td>
        <td style="text-align: justify; width: 84%">Tenant Repair and Maintenance Obligations </td>
        <td style="text-align: right; width: 5%">22</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">4.2</td>
        <td style="text-align: justify; width: 84%">Condition of Premises on Surrender</td>
        <td style="text-align: right; width: 5%"> 22</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">4.3</td>
        <td style="text-align: justify; width: 84%">Services </td>
        <td style="text-align: right; width: 5%">23</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 50%">ARTICLE 5 ASSIGNMENT AND SUBLETTING</td>
        <td style="width: 50%; text-align: right">24</td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">5.1</td>
        <td style="text-align: justify; width: 84%">General Prohibition on Transfers </td>
        <td style="text-align: right; width: 5%">24</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">5.2</td>
        <td style="text-align: justify; width: 84%">Other Permitted Transfers </td>
        <td style="text-align: right; width: 5%">27</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">5.3</td>
        <td style="text-align: justify; width: 84%">Non-Transfers </td>
        <td style="text-align: right; width: 5%">27</td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">5.4</td>
        <td style="text-align: justify; width: 84%">Conditions to Effectiveness </td>
        <td style="text-align: right; width: 5%">27</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">5.5</td>
        <td style="text-align: justify; width: 84%">Miscellaneous </td>
        <td style="text-align: right; width: 5%">27</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 50%">ARTICLE 6 INDEMNIFICATION; RELEASE; INSURANCE</td>
        <td style="width: 50%; text-align: right">29</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">6.1</td>
        <td style="text-align: justify; width: 84%">Indemnification and Release </td>
        <td style="text-align: right; width: 5%">29</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">6.2</td>
        <td style="text-align: justify; width: 84%">Insurance</td>
        <td style="text-align: right; width: 5%"> 30</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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      <tr style="vertical-align: top">
        <td style="width: 95%">ARTICLE 7 THIRD PARTIES</td>
        <td style="width: 5%; text-align: right">32</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">7.1</td>
        <td style="text-align: justify; width: 84%">Subordination, Attornment and Non-Disturbance </td>
        <td style="text-align: right; width: 5%">32</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">7.2</td>
        <td style="text-align: justify; width: 84%">Mortgagee&#8217;s Right to Cure </td>
        <td style="text-align: right; width: 5%">33</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">7.3</td>
        <td style="text-align: justify; width: 84%">Sale of the Premises </td>
        <td style="text-align: right; width: 5%">34</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">7.4</td>
        <td style="text-align: justify; width: 84%">Estoppel Certificates </td>
        <td style="text-align: right; width: 5%">34</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">7.5</td>
        <td style="text-align: justify; width: 84%">Liens </td>
        <td style="text-align: right; width: 5%">34</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 95%">ARTICLE 8 EVENTS OF DEFAULT &amp; REMEDIES</td>
        <td style="width: 5%; text-align: right">35</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">8.1</td>
        <td style="text-align: justify; width: 84%">Events of Default </td>
        <td style="text-align: right; width: 5%">35</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">8.2</td>
        <td style="text-align: justify; width: 84%">Remedies </td>
        <td style="text-align: right; width: 5%">36</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">8.3</td>
        <td style="text-align: justify; width: 84%">Landlord Default </td>
        <td style="text-align: right; width: 5%">39</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">8.4</td>
        <td style="text-align: justify; width: 84%">Non-Waiver </td>
        <td style="text-align: right; width: 5%">40</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 95%">ARTICLE 9 CASUALTY &amp; CONDEMNATION</td>
        <td style="width: 5%; text-align: right">40</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">9.1</td>
        <td style="text-align: justify; width: 84%">Casualty </td>
        <td style="text-align: right; width: 5%">40</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">9.2</td>
        <td style="text-align: justify; width: 84%">Waiver </td>
        <td style="text-align: right; width: 5%">42</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">9.3</td>
        <td style="text-align: justify; width: 84%">Total Condemnation </td>
        <td style="text-align: right; width: 5%">42</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">9.4</td>
        <td style="text-align: justify; width: 84%">Partial Condemnation </td>
        <td style="text-align: right; width: 5%">43</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
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        <td style="width: 5%; text-align: right">43</td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.1</td>
        <td style="text-align: justify; width: 84%">Notices </td>
        <td style="text-align: right; width: 5%">43</td>
      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
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      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.2</td>
        <td style="text-align: justify; width: 84%">Certain Representations</td>
        <td style="text-align: right; width: 5%"> 43</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.3</td>
        <td style="text-align: justify; width: 84%">Brokers </td>
        <td style="text-align: right; width: 5%">44</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.4</td>
        <td style="text-align: justify; width: 84%">No Waivers </td>
        <td style="text-align: right; width: 5%">44</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.5</td>
        <td style="text-align: justify; width: 84%">Future Development </td>
        <td style="text-align: right; width: 5%">45</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.6</td>
        <td style="text-align: justify; width: 84%">Other Provisions </td>
        <td style="text-align: right; width: 5%">46</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.7</td>
        <td style="text-align: justify; width: 84%">Interpretation</td>
        <td style="text-align: right; width: 5%"> 48</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.8</td>
        <td style="text-align: justify; width: 84%">Tenant&#8217;s Signage </td>
        <td style="text-align: right; width: 5%">49</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.9</td>
        <td style="text-align: justify; width: 84%">Choice of Law </td>
        <td style="text-align: right; width: 5%">49</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.10</td>
        <td style="text-align: justify; width: 84%">CASp Inspection </td>
        <td style="text-align: right; width: 5%">49</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">10.11</td>
        <td style="text-align: justify; width: 84%">Landlord Access </td>
        <td style="text-align: right; width: 5%">50</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 95%">ARTICLE 11 TENANT&#8217;S RIGHT OF FIRST OFFER</td>
        <td style="width: 5%; text-align: right">51</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">11.1</td>
        <td style="text-align: justify; width: 84%">Right of First Offer </td>
        <td style="text-align: right; width: 5%">51</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">11.2</td>
        <td style="text-align: justify; width: 84%">Tenant&#8217;s Competitors </td>
        <td style="text-align: right; width: 5%">52</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">11.3</td>
        <td style="text-align: justify; width: 84%">Transfers </td>
        <td style="text-align: right; width: 5%">52</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">11.4</td>
        <td style="text-align: justify; width: 84%">Termination </td>
        <td style="text-align: right; width: 5%">53</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">11.5</td>
        <td style="text-align: justify; width: 84%">Confidentiality </td>
        <td style="text-align: right; width: 5%">53</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 95%">ARTICLE 12 LIMITATION OF LIABILITY</td>
        <td style="width: 5%; text-align: right">53</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">12.1</td>
        <td style="text-align: justify; width: 84%">Landlord&#8217;s Liability </td>
        <td style="text-align: right; width: 5%">53</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 7%"></td>
        <td style="width: 4%">12.2</td>
        <td style="text-align: justify; width: 84%">Assignment of Rents </td>
        <td style="text-align: right; width: 5%">54</td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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      <tr style="vertical-align: top">
        <td style="width: 12%; padding-bottom: 10pt"><font style="font-size: 10pt">Schedule 1</font></td>
        <td style="width: 88%; padding-bottom: 10pt"><font style="font-size: 10pt">Example Showing Calculation of Base Rent</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit A</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Legal Description of the Premises</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit B</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Work Letter</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit C</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Form of Tenant Estoppel Certificate</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit D</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Form of Memorandum of Lease</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit E</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Form of SNDA</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit F</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Form of Non-Disclosure and Confidentiality Agreement</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit G</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Landlord Signage</font></td>
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        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit H</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Commencement and Termination Date Agreement</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit I</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Tenant Construction Manual</font></td>
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      <tr style="vertical-align: top">
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Exhibit J</font></td>
        <td style="padding-bottom: 10pt"><font style="font-size: 10pt">Tenant Standard Operating Procedures</font></td>
      </tr>

  </table>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">LEASE AGREEMENT</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">This Lease Agreement (this &#8220;<b>Lease</b>&#8221;), dated ___________, 2022 (the &#8220;<b>Effective Date</b>&#8221;), is made between Lots 21
    &amp; 22 Owner (DE) LLC, a Delaware limited liability company (&#8220;<b>Landlord</b>&#8221;), and Ionis Pharmaceuticals, Inc., a Delaware corporation (&#8220;<b>Tenant</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE 1&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>LEASE OF PREMISES; TERM</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Lease</u>. Landlord hereby leases to Tenant,
    and Tenant hereby leases from Landlord, the Premises for the Term. All of the terms and covenants of this Lease shall be effective as of the Effective Date. After the Commencement Date, Tenant and Landlord shall execute, acknowledge and deliver a
    written agreement in the form attached hereto as Exhibit H memorializing the Commencement Date, the Expiration Date, the original Term, and the commencement and termination dates of the Extension Terms if such are exercised.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>As Is; No Representations</u>. Tenant&#8217;s
    lease of the Premises is on an &#8220;AS IS WHERE IS&#8221; basis, and Landlord shall have no obligation to prepare the Premises for Tenant&#8217;s occupancy or to pay for or construct any improvements to the Premises, except for performance of the Landlord&#8217;s
    Construction Work as defined in the Work Letter (including with respect to any Warranty Issue [as defined in the Work Letter] arising after completion of Landlord&#8217;s Construction Work, to the extent required by the Work Letter) and with respect to
    payment of the TI Allowance as defined in the Work Letter and as otherwise expressly set forth in this Lease. Landlord has not made any representation or warranty to Tenant regarding (a) the condition or suitability of the Premises for the conduct of
    Tenant&#8217;s business (including, without limitation, any utilities serving the Premises, any structural components of the improvements or the condition of any Building system, except as otherwise expressly set forth in the Work Letter), (b) the
    restrictions that may affect the conduct of Tenant&#8217;s business in, or Tenant&#8217;s use of, the Premises, or any other rights or benefits under this Lease, (c) the suitability of the Premises for Tenant&#8217;s intended Permitted Use, or (d) compliance with
    Environmental Laws at the Premises or any environmental conditions at, or Hazardous Materials on, under, above, emanating to or from, or having emanated to or from, the Premises. TENANT EXPRESSLY WAIVES ANY WARRANTY OF CONDITION OR OF HABITABILITY OR
    SUITABILITY FOR OCCUPANCY, USE, HABITATION, FITNESS FOR A PARTICULAR PURPOSE OR MERCHANTABILITY, EXPRESS OR IMPLIED, RELATING TO THE PREMISES. Except in connection with the performance of Landlord&#8217;s Construction Work, as provided in the Work Letter,
    Tenant assumes full responsibility for all costs and expenses required to cause the Premises to comply with all Applicable Laws. &#8220;<b>Applicable Laws</b>&#8221; means all applicable present and future federal, state, municipal and local laws, codes,
    ordinances, rules and regulations of governmental authorities, committees, associations, or other regulatory committees, agencies or governing bodies having jurisdiction over the Premises or any portion thereof, Landlord or Tenant, including both
    statutory and common law and Environmental Laws. &#8220;<b>Environmental Laws</b>&#8221; means any applicable present and future federal, state and local laws, statutes, ordinances, rules, and regulations, as well as common law, relating to protection of human
    health, natural resources or the environment or governing the use, transport, or disposal of biological, bio-hazardous wastes, or radiological elements. The term &#8220;Environmental Laws&#8221; includes, but is not limited to, the Comprehensive Environmental
    Response, Compensation and Liability Act of 1980, as amended (&#8220;<b>CERCLA</b>&#8221;), 42 U.S.C. &#167;9601 et seq.; the Toxic Substance Control Act, 15 U.S.C. &#167;2601 et seq.; the Hazardous Materials Transportation Act, 49 U.S.C. &#167;5101 et seq.; the Resource
    Conservation and Recovery Act, 42 U.S.C. &#167;6901, et seq.; the Clean Water Act, 33 U.S.C. &#167;1251 et seq.; the Safe Drinking Water Act, 42 U.S.C. &#167;300f et seq.; the Clean Air Act, 42 U.S.C. &#167;7401 et seq.; Federal Water Pollution Control Act, 33 U.S.C. &#167;&#167;
    1251 et seq.; Clean Air Act, 42 U.S.C. &#167;&#167; 7401 et seq.; Emergency Planning and Community Right-To- Know Act, 42 U.S.C. &#167;&#167; 11001 et seq.; Occupational Safety and Health Act, 29 U.S.C. &#167;&#167; 65 et seq.; California Labor Code &#167;63.82, California Health and
    Safety Code &#167;25249.5, et seq., and all other applicable federal, state and local laws, regulations, ordinances, rules, and orders that are equivalent or similar to the laws recited above, or otherwise relate to human health, natural resources or the
    environment, in each case together with their implementing regulations, guidelines, rules, or orders, and all state, regional, county, municipal, and other local laws, regulations, ordinances, rules, and orders that are equivalent or similar to the
    federal and state laws recited above.&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Holdover</u>. If Tenant retains possession of
    any portion of the Premises after the Termination Date (as hereinafter defined) without Landlord&#8217;s written consent, then Landlord shall be entitled to exercise all remedies that may be available under this Lease or at law or in equity, and Tenant shall
    (a) be a tenant at sufferance only, (b) be liable to perform all of the obligations of Tenant set forth in this Lease, and (c) (i) for the first ninety (90) days following the Termination Date, pay Base Rent at a rate of one hundred twenty-five percent
    (125%) of the monthly Base Rent in effect immediately prior to the Termination Date, and (ii) for each month thereafter, pay Base Rent at a rate of one hundred fifty percent (150%) of the monthly Base Rent in effect immediately prior to the Termination
    Date, prorated on a daily basis. If Tenant retains possession of any portion of the Premises for more than thirty (30) days following the Termination Date without Landlord&#8217;s written consent, Tenant shall also pay to Landlord all damages, direct,
    consequential, or indirect, sustained by Landlord by reason of any such holding over. Otherwise, such holding over shall be on the terms and conditions set forth in this Lease as far as applicable. &#8220;<b>Termination Date</b>&#8221; means the date on which this
    Lease terminates for any reason, including the Expiration Date. The provisions of this <u>Section 1.3</u> shall not operate as a waiver by Landlord of any right of re-entry provided in this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 1.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Extension Option</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">1.4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Exercise of Extension Option</u>. Tenant
    shall have two (2) successive options (each, an &#8220;<b>Extension Option</b>&#8221;) to extend the Term of this Lease for a period of five (5) years each (each, an &#8220;<b>Extension Period</b>&#8221;), on the same terms and conditions in effect under this Lease
    immediately prior to the Extension Period, except that Base Rent shall be determined as set forth below and Tenant shall have no further right to extend the Term of this Lease after the end of the second (2<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup>) Extension Period; provided, however, it shall be a condition of Tenant&#8217;s exercise of the Extension Option that Tenant also exercise the corresponding &#8220;Extension Option&#8221; as defined in the Companion Lease.
    If Tenant exercises an Extension Option, such extension shall apply to the entire Premises. Tenant may exercise an Extension Option only by giving Landlord irrevocable and unconditional written notice thereof (the &#8220;<b>Extension Notice</b>&#8221;) on or
    before the date which is twelve (12) months prior to the commencement date of each applicable Extension Period and such Extension Period shall commence on the day immediately succeeding the expiration date of the preceding Term or the preceding
    Extension Period, as the case may be, and shall end at midnight Eastern Time on the last day of the applicable Extension Period. Such exercise shall, at Landlord&#8217;s election, be null and void if any Event of Default shall have occurred and is continuing
    at the date of such notice. Upon delivery of the Extension Notice, Tenant shall be irrevocably bound to lease the Premises for the Extension Period. If Tenant shall fail to timely exercise the Extension Option in accordance with the provisions of this
    <u>Section 1.4</u>, then the Extension Option shall terminate, and shall be null and void and of no further force and effect. If this Lease or Tenant&#8217;s right to possession of the Premises shall terminate in any manner whatsoever before Tenant shall
    exercise the Extension Option, then immediately upon such termination the Extension Option shall simultaneously terminate and become null and void. Time is of the essence with regard to this <u>Section 1.4</u>.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">1.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Base Rent Determination</u>. The Base Rent
    starting on the Commencement Date of each Extension Period and continuing for sixty (60) months thereafter will be ninety-five percent (95%) of the then-prevailing market rate for new leases for comparable life sciences office and lab space to the
    Premises in comparable buildings to the Building in the Market Area (defined below) that a willing, comparable, non-equity tenant (excluding sublease and assignment transactions) would pay, and a willing, comparable landlord would accept, at arm&#8217;s
    length, for a similar life sciences laboratory and research space in a first-class or &#8220;Class A&#8221; property (&#8220;<u>Fair Market Rent</u>&#8221;); provided, however, in no event shall the Fair Market Rent rate per month for the first year of each Extension Period
    be less than 103% of the Base Rent rate for the last month of the immediately preceding portion of the Term. Thereafter, escalations in the Base Rent shall be established using standard market escalations in the determination of Fair Market Rent, but
    in no event shall escalations in Base Rent be increased by less than three percent (3%) on each annual anniversary of the Commencement Date of the Extension Term. Fair Market Rent will reflect all monetary and non-monetary considerations and other
    relevant factors taken into account for comparable transactions, including, without limitation, the location of the Premises, age, quality and layout of the existing improvements in the Premises, brokerage commissions, improvements paid for by tenant
    improvement allowances, moving allowances, and all other relevant tenant concessions. Fair Market Rent will be adjusted to take into account the size of the Premises, the length of the Extension Period, and the credit of Tenant. The term &#8220;<b>Market
      Area</b>&#8221; means the real estate market area that includes Carlsbad, Sorrento Valley, Sorrento Mesa, University Town Center, and Delmar Heights.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">1.4.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Fair Market Rent</u>. Landlord will notify
    Tenant of its determination of the Fair Market Rent (consistent with the methodology reflected above) for the applicable Extension Period no later than ninety (90) days prior to the commencement date of the applicable Extension Period. If Tenant
    delivers written notice to Landlord within ten (10) business days after its receipt of Landlord&#8217;s determination of Fair Market Rent whereby Tenant disagrees with Landlord&#8217;s determination of the Fair Market Rent, Tenant shall include in its notice
    Tenant&#8217;s determination of the Fair Market Rent, and Landlord and Tenant will diligently and in good-faith confer for a period of thirty (30) days thereafter (the &#8220;<b>Negotiation Period</b>&#8221;) in an attempt to agree on the Fair Market Rent. If Landlord
    and Tenant are unable to agree on the Fair Market Rent during the Negotiation Period, then, within five (5) business days after the expiration of such period, Landlord and Tenant shall jointly appoint an independent arbitrator (the &#8220;<b>Arbitrator</b>&#8221;)
    who shall not have previously been employed by or otherwise worked with either Landlord or Tenant with experience in real estate activities, including at least ten (10) years&#8217; experience serving as a broker, appraiser and/or attorney in leasing
    transactions involving commercial life sciences laboratory and research space of comparable size and Class A quality to the Premises (collectively, the &#8220;Qualifications&#8221;), which Arbitrator shall, within twenty (20) days following the Arbitrator&#8217;s
    appointment, determine and report in writing to Landlord and Tenant the by selecting either Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent for the Extension Period, according to whichever of the applicable determinations is closer to the
    Fair Market Rent, as determined by the Arbitrator. If Landlord and Tenant cannot agree on the Arbitrator in accordance with the foregoing, Landlord or Tenant may apply to the American Arbitration Association to appoint the Arbitrator in accordance with
    the aforementioned criteria. The Arbitrator shall have no discretion other than to select Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent as aforesaid. The costs of the Arbitrator shall be shared equally by Landlord and Tenant, and each of
    Landlord and Tenant shall reasonably cooperate with the Arbitrator in providing documentation and any other reasonable evidence regarding how Landlord or Tenant, as applicable, arrived at its determination of the Fair Market Rent. If the Renewal Period
    commences prior to the final determination of the Fair Market Rent, Tenant shall pay to Landlord the monthly rate in effect immediately prior to the commencement of the applicable Renewal Period, subject to adjustment upon resolution of such dispute.&#160;</p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">1.4.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>General</u>. Notwithstanding any provision
    of this Section to the contrary, the Extension Option shall be void, at Landlord&#8217;s election, if (i) Tenant is in default hereunder, after any applicable notice and cure periods have expired, at the time Tenant elects to extend the Term or at the time
    the Term would expire but for such extension, or (ii) any Transfer has occurred under Article 5 of the Lease (other than a Permitted Transfer, or a sublease(s) comprising less than twenty-five percent (25%) of the Premises).</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE 2</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">RENT</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in"> 2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Base Rent and Additional Rent</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall pay to Landlord, without notice
    or demand and without deduction or set-off of any amount for any reason whatsoever, the annual Base Rent in equal monthly payments, in advance, beginning on the Commencement Date, and thereafter on or before the first day of each full calendar month
    during the Term. Base Rent as well as any other amounts payable by Tenant to Landlord under the terms of this Lease shall be paid by wire or electronic transfer of funds pursuant to directions provided to Tenant by Landlord. In addition to Base Rent,
    Tenant shall pay to Landlord a property management fee (&#8220;<b>Management Fee</b>&#8221;) of one percent 1%) of the gross annual revenue form the Premises, which amount shall be paid in equal monthly payments on the same date and in the same manner as Base
    Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>No later than one hundred eighty (180) days
    after the Delivery Date, Landlord will provide written notice (the &#8220;<b>Estimated Calculation Notice</b>&#8221;) of Landlord&#8217;s calculation of the initial amount of Base Rent using a preliminary estimate of the Construction Costs, to the extent they are known
    at the time of the Estimated Calculation Notice. Until the Landlord provides the Final Calculation Notice (as defined below), commencing on the Commencement Date, Tenant shall pay the estimated annual Base Rent amount set forth in the Estimated
    Calculation Notice in equal monthly installments for the applicable month(s). On or before the date that is one hundred eighty (180) days after the Commencement Date, Landlord will provide written notice (the &#8220;<b>Final Calculation Notice</b>&#8221;) of
    Landlord&#8217;s calculation of the initial amount of Base Rent using the final amount of Construction Costs. Tenant will pay any underpayment of Base Rent, and Landlord will credit to Tenant&#8217;s account any overpayment of Base Rent, based upon the difference
    between the estimated Base Rent actually paid by Tenant and the amount of Base Rent set forth in the Final Calculation Notice. If the Commencement Date is not the first day of a calendar month, Tenant shall pay to Landlord on the Commencement Date the
    prorated Base Rent for period from the Commencement Date until the end of the calendar month in which the Commencement Date occurs. Base Rent due for any partial calendar month at the end of the Term shall also be prorated and paid on the first day of
    such calendar month. Tenant shall pay to Landlord all items of Rent (as defined below), without deduction or offset and without notice or demand (except as specifically provided in this Lease in respect of Additional Rent (as defined below)), and
    Tenant shall deliver such payments to the payment address set forth in the Basic Lease Information, or to such other person, at such other place, or in such other manner as Landlord may designate by giving to Tenant Notice (as defined below) thereof. &#8220;<b>Additional






      Rent</b>&#8221; means all other amounts payable by Tenant to Landlord in accordance with this Lease, other than Base Rent. &#8220;<b>Rent</b>&#8221; means all amounts payable by Tenant to Landlord in accordance with this Lease, including, but not limited to Base Rent
    and Additional Rent.&#160;</p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord shall, on or within thirty (30) days
    prior to each Adjustment Date, calculate the Escalation after the United States Department of Labor publishes the Index on which the amount of the increase will be based. Landlord&#8217;s determination of the Escalation shall be binding absent manifest
    error. Landlord shall give written notice of the Escalation, multiplied by the number of installments of rent due under this Lease since the Adjustment Date. Tenant shall pay this amount, together with the monthly rent next becoming due under this
    Lease, and shall thereafter pay the monthly rent due under this Lease at this increased rate, which shall constitute Base Rent. Landlord&#8217;s failure to make the required calculations promptly shall not be considered a waiver of Landlord&#8217;s rights to
    adjust the monthly Base Rent due, nor shall it affect Tenant&#8217;s obligations to pay the increased Base Rent, subject to this Section 2.1.3. If Landlord does not deliver its calculation of the Escalation within twelve (12) months after the applicable
    Adjustment Date, Tenant may provide Landlord with a written request for the calculation of the Escalation, and, if Landlord fails to provide the calculation of Escalation (which request shall include, in bold and prominent print on the first page, a
    notation that &#8220;<b>FAILURE TO RESOND TO THIS REQUEST WITHIN 30 DAYS MAY RESULT IN THE LOSS OF RIGHTS PURSUANT TO SECTION 2.1.3 OF THE LEASE</b>&#8221;) within thirty (30) days after Tenant&#8217;s written request, Tenant shall not be required to so pay the
    increased Base Rent in arrearage for the applicable period based on an Escalation; provided, however, the foregoing waiver of Tenant&#8217;s obligation to pay arrearage amounts for the applicable period shall not affect Landlord&#8217;s calculation of any future
    Escalations. If the Index is changed so that the base year differs from that in effect on the Commencement Date, the Index shall be converted in accordance with the conversion factor published by the United States Department of Labor, Bureau of Labor
    Statistics. If the Index is discontinued or revised during the Term, the government index or computation with which it is replaced shall be used to obtain substantially the same result as if the Index had not been discontinued or revised. The &#8220;<b>Adjustment







      Date</b>&#8221; means the first anniversary of the Commencement Date and on each successive anniversary thereafter during the Term, including any exercised Extension Period.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in"> 2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Expenses; Taxes; Insurance Expenses</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">2.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Expenses</u>. Except as provided in the
    Work Letter regarding any Warranty Issue, Tenant shall perform all obligations with respect to the maintenance, operation, repair and replacement of the Premises and shall pay directly for all costs and expenses incurred in connection therewith,
    including, but not limited to: all insurance, maintenance, repair and replacement of any improvements (including, without limitation, the Building, the structural and nonstructural components of the Building, the Building systems, equipment (owned and
    maintained), the foundation, roof, walls, heating, ventilation, air conditioning, plumbing, electrical, mechanical, utility (owned and maintained) and safety systems, paving and parking areas, roads and driveways); maintenance of exterior areas such as
    gardening and landscaping, snow removal and signage; maintenance and repair of roof membrane, flashings, gutters, downspouts, roof drains, skylights and waterproofing; painting; lighting; cleaning; refuse removal; security; utilities for, or the
    maintenance of, outside areas; Premises personnel costs; rentals or lease payments paid by Tenant for rented or leased personal property used in the operation or maintenance of the Premises; and fees for required licenses and permits, including in
    order to operate for the Permitted Use.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">2.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Taxes</u>. Subject to Tenant&#8217;s right to
    contest Taxes as set forth below, Tenant will pay directly all Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable. Landlord and Tenant shall cooperate to place all Taxes in the name of Tenant,
    however, if and to the extent any Taxes are billed to Landlord, then Tenant shall pay the same upon receipt of such bill from Landlord and provide Landlord with evidence of such payment promptly thereafter. In any event, Tenant shall pay all Taxes
    prior to the date due. &#8220;<b>Taxes</b>&#8221; means all real property taxes and other assessments on the Premises, including, but not limited to, real estate taxes, personal property taxes, transfer taxes, documentary stamps or taxes, fees, assessments and
    other charges of any kind or nature, whether general, special, ordinary, or extraordinary (without regard to any different fiscal year used by such governmental authority) that are levied in respect of this Lease or the Premises (or Landlord&#8217;s interest
    therein), or in respect of any improvement, fixture, equipment, or other property of Landlord, real or personal, located at the Premises, and used in connection with operation of the Premises. Tenant and Landlord acknowledge that Proposition 13 was
    adopted by the voters of the State of California in the June 1978 election (&#8220;<b>Proposition 13</b>&#8221;) and that assessments, taxes, fees, levies and charges may be imposed by governmental agencies for such services as fire protection, street, sidewalk
    and road maintenance, refuse removal and for other governmental services formerly provided without charge to property owners or occupants, and, in further recognition of the decrease in the level and quality of governmental services and amenities as a
    result of Proposition 13, Taxes shall also include any governmental or private assessments or contribution towards a governmental or private cost-sharing agreement charged to the Premises for the purpose of augmenting or improving the quality of
    services and amenities normally provided by governmental agencies. Taxes shall not include (i) Landlord&#8217;s corporate franchise taxes, estate taxes, inheritance taxes or net income taxes, or (ii) transfer taxes or other taxes incurred in connection with
    Landlord&#8217;s sale of the Premises or any interest therein, other than taxes resulting from Proposition 13 reassessment. Tenant shall furnish to Landlord, within thirty (30) days after the last day when any Tax must be paid by Tenant as provided in this
    Section 2.2.2, official receipt of the appropriate taxing authority or other proof satisfactory to Landlord, evidencing the payment thereof. Tenant shall have the right, at Tenant&#8217;s sole cost and upon reasonable prior notice to Landlord, to initiate
    and prosecute any proceeding for the purpose of contesting the assessed valuation of the Premises or any personal property for tax purposes in good faith; provided, that this right to contest shall not be deemed or construed to relieve, modify or
    extend Tenant&#8217;s obligation to pay any Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable and that prior to any such contest, Tenant (a) pays the Tax under protest, (b) obtains and maintains a stay of
    all proceedings for enforcement and collection by posting a bond or other security required by law, or (c) if Tenant lawfully withholds payments of any contested amounts of Taxes during the contest, Tenant has or establishes unrestricted cash reserves
    to be held by Landlord in an amount equal to 125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contest; provided, however, that Landlord shall (1) promptly release such
    reserve upon resolution of such contest, and/or (2) use such reserve to pay Taxes directly to the applicable taxing authority following resolution of such contest. Tenant shall provide Landlord with all notices received or sent to the taxing
    authorities, as well as regular updates relating to any such contest and afford Landlord an opportunity to participate in all such proceedings. Tenant shall indemnify and defend Landlord and save Landlord harmless from all losses, judgments, costs
    (including without limitation, attorneys&#8217; fees), liabilities and expenses incurred in connection with such proceedings and shall, promptly after the final determination of such contest, fully pay and discharge the amounts which shall be levied,
    assessed, charged or imposed or be determined to be payable therein or in connection therewith, together with all penalties, fines, costs and expenses thereof or in connection therewith). Landlord shall have the right to (a) contest or dispute any
    Taxes (or file an appeal related thereto), without Tenant&#8217;s prior written consent, at Landlord&#8217;s sole cost and expense, or (b) request that Tenant contest or dispute such Taxes (or file an appeal related thereto), in which event, Tenant, in Tenant&#8217;s
    sole discretion, may agree to contest or dispute such Taxes, at Tenant&#8217;s sole cost and expense. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord, Landlord, at its option, may require Tenant to make monthly
    estimated payments to Landlord on account of Taxes. The monthly payments shall be one twelfth (1/12th) of the amount of Taxes due for the applicable year as reasonably estimated by Landlord and shall be payable as Additional Rent on or before the first
    day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. So long as no Event of Default is then continuing, any amounts received by Landlord pursuant to the immediately
    preceding sentence shall be disbursed to Tenant by Landlord for payment to the applicable taxing authority (or paid to the applicable taxing authority directly by Landlord) when directed by Tenant, accompanied by evidence of the amount due. Upon
    Tenant&#8217;s request, Landlord shall provide Tenant with evidence of any such payments of Taxes made directly by Landlord.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in"><font style="font-family: Times New Roman, Times, Serif">2.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Insurance</u>. Tenant shall
    reimburse or, at Landlord&#8217;s request, pay directly, all premiums, deductibles, and other costs incurred by Landlord in connection with obtaining and maintaining the insurance coverage described in <u>Section 6.2.1</u> below (collectively, the &#8220;<b>Insurance






      Expenses</b>&#8221;). Tenant shall pay the Insurance Expenses no later than fifteen (15) days after demand. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord, Landlord, at its option, may require Tenant to make
    monthly estimated payments to Landlord on account of Insurance Expenses. The monthly payments shall be one twelfth (1/12th) of the amount of Insurance Expenses due for the applicable year as reasonably estimated by Landlord and shall be payable as
    Additional Rent on or before the first day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. If Landlord requires monthly payments of the Insurance Expenses, Landlord
    will use reasonable efforts to provide a statement reconciling such payments within ninety (90) days after the end of each calendar year, and any underpayments shall paid by Tenant within fifteen (15) days after Tenant&#8217;s receipt of the statement, and
    any overpayments shall be credited to the next payment of Rent that becomes due under the Lease.</p>
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  </p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in"> 2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Net Lease.</u></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Absolute Triple Net Lease</u>. It is
    intended by the parties that this Lease be an absolute &#8220;triple net lease,&#8221; imposing upon Tenant the obligation to pay all charges of every kind and nature in connection with the use, operation, management, maintenance, repair, and occupancy of the
    Premises, whether or not recited herein and whether foreseeable or unforeseeable, including, but not limited to, utilities, fees, costs, real estate taxes, sales and use taxes, all operation, management, maintenance and repair costs associated with the
    Premises and the improvements located thereon and costs of compliance with Environmental Laws, except as expressly provided in this Lease. Tenant shall pay to Landlord, net throughout the Term, the Rent due hereunder free of any offset, abatement, or
    other deduction whatsoever, without notice or demand. Except to the extent due to the gross negligence or willful misconduct of, or breach of contract by, Landlord or any of Landlord&#8217;s assignees, agents, servants, employees, invitees and contractors
    (or any of Landlord&#8217;s assignees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Landlord Parties</b>&#8221;; any of them, a &#8220;<b>Landlord Party</b>&#8221;), Tenant assumes the sole responsibility for the condition, use,
    operation, maintenance, management and compliance with Environmental Laws of the Premises, and Landlord shall have no responsibility in respect thereof and shall have no liability for damage to Tenant&#8217;s personalty on any account or for any reason
    whatsoever. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant shall not be required to pay, or reimburse Landlord for: (i) depreciation charges, penalties, premiums, interest and principal payments on mortgages and other
    debt costs, ground rental payments and real estate brokerage and leasing commissions incurred by Landlord; (ii) costs incurred for Landlord&#8217;s general overhead and any property or asset management fee other than as expressly set forth in this Lease;
    (iii) costs of selling or financing any of Landlord&#8217;s interest in the Premises; (iv) costs incurred by Landlord which are reimbursed by property insurance proceeds actually received by Landlord where such proceeds result from a claim subject to the
    provisions of Section 6.2.3. below; and (v) reserves in excess of commercially reasonable amounts for comparable properties (and such reserves shall only be payable by Tenant if required by Landlord&#8217;s lender or in accordance with commercially
    reasonable business practices for comparable properties).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Payments to Third Parties</u>. Subject to
    <u>Section 2.2.3(c)</u> below, Landlord and Tenant recognize that there may be recurring payments to third parties, including governmental entities, for various items including inspections of storm water retention areas, inspections of pump stations,
    fees for storm water runoff, and assessments for maintenance and repairs under a Title Instrument (as defined below). Tenant is solely responsible for paying any fees or expenses imposed by governmental regulations or third parties, including those
    that may be required to obtain, modify and maintain compliance with any permits, licenses and approvals required by Applicable Laws, including for the use of and operation at the Premises by Tenant for the Permitted Use, or allocated to the Premises
    under any such Title Instrument. Tenant acknowledges that matters of the type contemplated by this Section may not be known to Landlord until after this Lease has been signed by Landlord and Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Title Instruments</u>. In addition to the
    foregoing, during the term of this Lease, Tenant shall timely perform all obligations of the owner of the Premises under, and pay all expenses which the owner of the Premises may be required to pay in accordance with any declarations, covenants,
    conditions and restrictions or reciprocal easement agreements or any other documents or instruments that are of record now and affect the Premises (or of record in the future if created or filed by or with the consent of Tenant), including, without
    limitation, any documents or instruments recorded in connection with any Future Development (referred to collectively herein as the &#8220;<b>Title Instruments</b>&#8221;); provided, however, Tenant need not pay any debt service on loans that encumber the fee
    estate and that do not encumber Tenant&#8217;s leasehold estate and Tenant need not pay any rent on any lease that is senior in priority to this Lease. Tenant promptly shall comply with all of the terms and provisions of all Title Instruments, including all
    insurance requirements, regardless of whether any such requirements exceed the requirements otherwise set forth in this Lease. Notwithstanding the foregoing, except as provided in Section 10.5, Landlord shall not enter into new Title Instruments or
    modify existing Title Instruments during the Term without Tenant&#8217;s prior written consent, which may be withheld in Tenant&#8217;s reasonable discretion; provided, however, that Tenant&#8217;s prior written consent shall not be required with respect to (i) any
    financing obtained by Landlord secured by Landlord&#8217;s interest in the Premises, (ii) Title Instruments necessary to effectuate transfers to third-party purchasers of the Premises, or (iii) any new Title Instruments or the modification of existing Title
    Instruments that do not (x) materially and adversely affect Tenant&#8217;s use or occupancy of the Premises or (y) impose any fees or costs that would be payable by Tenant unless Landlord agrees to pay such fees.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify">2.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Interest and Late Charge</u>. If Tenant fails
    to pay Rent as and when due and such failure continues for three (3) business days following written notice from Landlord, then, together with each payment of Rent that Tenant pays to Landlord after such payment is due, Tenant shall pay to Landlord the
    Late Charge (as defined below) and interest calculated on the amount of such payment over the period commencing on the day immediately following the day on which such payment was due and ending on the day on which Tenant pays to Landlord such payment
    at the rate of the lesser of six percent (6%) over the &#8220;Prime Rate&#8221; announced from time to time by Bank of America or its successor or the maximum lawful rate of interest. Notwithstanding the foregoing, Landlord shall not be required to provide prior
    notice of Tenant&#8217;s failure to pay Base Rent or any recurring obligation to pay Rent more than once during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be subject to the Late Charge and default interest provided
    above if Tenant fails to pay the amount when due and such failure continues for three (3) business days after the due date. &#8220;<b>Late Charge</b>&#8221; means, in respect of any such payment, five percent (5%) of such payment. In addition, Tenant shall pay to
    Landlord a reasonable fee for any checks returned by Tenant&#8217;s bank for any reason.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> 2.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Security Deposit/Letter of Credit</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Concurrently with Tenant&#8217;s execution of this
    Lease, and in lieu of a cash security deposit, Tenant shall provide a letter of credit (the &#8220;<b>Letter of Credit</b>&#8221;) in the amount set forth as the &#8220;Security Deposit/Letter of Credit&#8221; in the Basic Lease Information. Any cash security deposit drawn
    from the Letter of Credit may be mingled with other funds of Landlord and no fiduciary relationship shall be created with respect to such deposit, nor shall Landlord be liable to pay Tenant interest thereon. The initial amount of the Letter of Credit
    shall be determined using Landlord&#8217;s reasonable estimate of the Base Rent as the time of the execution of the Lease, and within thirty (30) days after the Final Calculation Notice the Letter of Credit shall be modified or reissued in the required
    amount as determined using the Base Rent set forth in the Final Calculation Notice. Provided that Tenant has not assigned its interest in this Lease (other than with respect to a Permitted Transfer) and there is no uncured Event of Default, on (i) the
    second (2<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup>) anniversary of the Commencement Date and (ii) the fourth (4<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>) anniversary of
    the Commencement Date, Tenant may notify Landlord in writing (the &#8220;<b>Reduction Request</b>&#8221;) and request the reduction of the Letter of Credit by an amount equal to two (2) months of the initial Base Rent (the &#8220;<b>Reduction Amount</b>&#8221;). Provided that
    the conditions above have been satisfied at the time Landlord receives a Reduction Request, Landlord shall instruct the Bank, within sixty (60) days after Landlord&#8217;s receipt of the Reduction Request, that the Letter of Credit may be reduced by the
    Reduction Amount. In no event shall the Letter of Credit be reduced to an amount less than six (6) months of the initial Base Rent.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Letter of Credit (i) shall be irrevocable
    and shall be issued by a commercial bank that has a financial condition reasonably acceptable to Landlord and that is otherwise an Eligible Bank (as defined below) and has an office in San Francisco, California that accepts requests for draws on the
    Letter of Credit; provided, Silicon Valley Bank shall be deemed an approved issuer of the Letter of Credit so long as Silicon Valley Bank remains an Eligible Bank, (ii) shall require only the presentation to the issuer (which may be in a location other
    than San Francisco if permitted on the basis of a fax or electronic submittal only) a certificate of the holder of the Letter of Credit stating that Landlord is entitled to draw on the Letter of Credit pursuant to the terms of the Lease, (iii) shall be
    payable to Landlord or its successors in interest as the Landlord and shall be freely transferable without cost to any such successor or any lender holding a collateral assignment of Landlord&#8217;s interest in the Lease, (iv) shall be for an initial term
    of not less than one year and contain a provision that such term shall be automatically renewed for successive one-year periods unless the issuer shall, at least forty five (45) days prior to the scheduled expiration date, give Landlord notice of such
    nonrenewal, (v) shall be transferrable by Landlord without any cost to Landlord or the transferee (or, if there is a transfer fee, Tenant shall pay such fee and such transfer shall not be conditioned upon payment of such fee), and (vi) shall otherwise
    be in form and substance reasonably acceptable to Landlord. Notwithstanding the foregoing, the term of the Letter of Credit for the final period shall be for a term ending not earlier than the date forty-five (45) days after the last day of the Term.
    In the event that the issuer ceases to be reasonably acceptable to Landlord, due to a deterioration in its financial condition or change in status that threatens to compromise Landlord&#8217;s ability to draw on the Letter of Credit as determined in good
    faith by Landlord or otherwise by its failure to be an Eligible Bank, then Tenant shall provide a replacement Letter of Credit from an issuer satisfying the terms of this Section <u>2.5.2</u> within thirty (30) days after Landlord&#8217;s notice of such
    event. &#8220;<b>Eligible Bank</b>&#8221; shall mean shall mean a commercial or savings bank organized under the laws of the United States or any state thereof or the District of Columbia and having total assets in excess of $1,000,000,000.00 that shall be a
    financial institution having a rating of not less than BBB or its equivalent by Standard and Poors Corporation and subject to a Thompson Watch Rating of C or better.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Letter of Credit shall be held by, or for
    the benefit of Landlord, as security for the performance of the provisions hereof by Tenant, and if the Letter of Credit or portion thereof is applied by Landlord for the payment of any Rent or any other sum in default, then Tenant shall, upon demand
    therefor, restore the Letter of Credit to its original amount as provided in <u>Section 2.5.1</u> above. Tenant hereby irrevocably waives and relinquishes any and all rights, benefits, or protections, if any, Tenant now has, or in the future may have
    under any provision of law which (i) establishes the time frame by which a landlord must refund a security deposit under a lease, or (ii) provides that a landlord may claim from a security deposit only those sums reasonably necessary to remedy defaults
    in the payment of rent, or to repair damage caused by a tenant or to clean the subject premises, as required and subject to the provisions of this Lease. Tenant acknowledges and agrees that (A) any statutory time frames for the return of a security
    deposit are superseded by the express period identified in this <u>Section 2.5</u>, and (B) rather than be so limited, Landlord may claim from the security deposit (i) any and all sums expressly identified in this <u>Section 2.4</u>, above, and (ii)
    any additional sums reasonably necessary to compensate Landlord for any and all losses or damages caused by Tenant&#8217;s default of this Lease, including, but not limited to, all damages or rent due upon termination of this Lease.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord shall be entitled to draw upon the
    Letter of Credit for its full amount or any portion thereof if (a) Tenant shall fail to perform any of its obligations under the Lease after the expiration of any applicable notice and cure period, or fail to perform any of its obligations under the
    Lease and transmittal of a default notice or the running of any cure period is barred or tolled by Applicable Law, or fail to perform any of its obligations under the Lease and any applicable notice and cure period would expire after the expiration of
    the Letter of Credit, (b) not less than thirty (30) days before the scheduled expiration of the Letter of Credit, Tenant has not delivered to Landlord a new Letter of Credit in accordance with this Section; provided no such delivery shall be required
    if the Letter of Credit provides for automatic renewals in compliance with <u>Section 2.5.2</u>, and the issuer of the Letter of Credit has not sent a notice of non-renewal, or (c) as provided in Schedule 8 to the Work Letter attached as Exhibit D.
    Without limiting the generality of the foregoing, Landlord may, but shall not be obligated to, draw on the Letter of Credit from time to time in the event of a bankruptcy filing by or against Tenant and/or to compensate Landlord, in such order as
    Landlord may determine, for all or any part of any unpaid rent, any damages arising from any termination of the Lease in accordance with the terms of the Lease, and/or any damages arising from any rejection of the Lease in a bankruptcy proceeding
    commenced by or against Tenant. Landlord may, but shall not be obligated to, apply the amount so drawn to the extent necessary to cure Tenant&#8217;s failure.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Any amount of the Letter of Credit drawn in
    excess of the amount applied by Landlord to cure any such failure or as provided on Schedule 8 to the Work Letter shall be held by Landlord as a cash security deposit for the performance by Tenant of its obligations under the Lease. If Tenant shall
    fail to perform any of its obligations under the Lease, Landlord may, but shall not be obliged to, apply the cash security deposit to the extent necessary to cure Tenant&#8217;s failure. After any such application by Landlord of the Letter of Credit or cash
    security deposit, as the case may be, Tenant shall reinstate the Letter of Credit to the amount originally required to be maintained under the Lease, within ten (10) business days of Landlord&#8217;s demand. Provided that Tenant is not then in default under
    the Lease, and no condition exists or event has occurred that after the expiration of any applicable notice or cure period would constitute such a default, within forty five (45) days after the later to occur of (i) the payment of the final Rent due
    from Tenant or (ii) the later to occur of the Term Expiration Date or the date on which Tenant surrenders the Premises to Landlord in compliance with Section 20 of the Lease, the Letter of Credit and any cash security deposit, to the extent not applied
    or held by Landlord for the purposes described in Schedule 8 to the Work Letter, shall be returned to the Tenant, without interest, and Landlord, upon request, shall confirm termination of the Letter of Credit with the issuer thereof.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>In the event of a sale of the Building or
    lease, conveyance or transfer of the Building, Landlord shall transfer the Letter of Credit or cash security deposit to the transferee. Upon such transfer, the transferring Landlord shall be released by Tenant from all liability for the return of such
    security, and Tenant agrees to look to the transferee solely for the return of said security. The provisions hereof shall apply to every transfer or assignment made of the security to such a transferee. Tenant further covenants that it will not assign
    or encumber or attempt to assign or encumber the Letter of Credit or the monies deposited herein as security, and that neither Landlord nor its successors or assigns shall be bound by any assignment, encumbrance, attempted assignment or attempted
    encumbrance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.95in">2.5.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord and Tenant acknowledge and agree
    that in no event or circumstance shall the Letter of Credit, any renewal thereof or substitute therefor or the proceeds thereof be (i) deemed to be or treated as a security deposit within the meaning of California Civil Code Section 1950.7, (ii)
    subject to the terms of such Section 1950.7, or (iii) intended to serve as a security deposit within the meaning of such Section 1950.7. The parties hereto (A) recite that the Letter of Credit is not intended to serve as a security deposit and such
    Section 1950.7 and any and all other laws, rules and regulations applicable to security deposits in the commercial context (&#8220;<b>Security Deposit Laws</b>&#8221;) shall have no applicability or relevancy thereto, and (B) waive any and all rights, duties and
    obligations either party may now or, in the future, will have relating to or arising from the Security Deposit Laws. Notwithstanding the foregoing, to the extent California Civil Code 1950.7 in any way: (a) is determined to be applicable to this Lease
    or the Letter of Credit (or any proceeds thereof); or (b) controls Landlord&#8217;s rights to draw on the Letter of Credit or apply the proceeds of the Letter of Credit to any amounts due under this Lease or any damages Landlord may suffer following
    termination of this Lease, then Tenant fully and irrevocably waives the benefits and protections of Section 1950.7 of the California Civil Code, it being agreed that Landlord may recover from the Letter of Credit (or its proceeds) all of Landlord&#8217;s
    damages under this Lease and California law including, but not limited to, any damages accruing upon the termination of this Lease in accordance with this Lease and Section 1951.2 of the California Civil Code.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE 3&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>USE, COMPLIANCE WITH LAWS, HAZARDOUS MATERIALS, DOGS</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Use</u>. Tenant shall use the Premises solely
    for the Permitted Use, in a manner consistent with first-class life science buildings, and shall comply (and ensure that the Premises at all times comply) with all Applicable Laws. Tenant shall be solely responsible for the securing, modifying,
    maintaining, and compliance with any and all permits, licenses and approvals required or that may be required or otherwise in effect for the Permitted Use and under Environmental Laws in connection with Tenant&#8217;s use and operation of the Premises.
    Tenant shall not commit, or allow to commit, any waste of or injury to the Premises or create, maintain or exacerbate any nuisance thereon or therefrom. Landlord agrees to reasonably cooperate with Tenant, at Tenant&#8217;s sole cost and expense, in
    obtaining any permits, licenses and approvals required by Applicable Laws for the use of and operation at the Premises by Tenant for the Permitted Use, including, without limitation, by executing or joining in the execution of such applications and
    other documentation (the form and content of which shall be subject to Landlord&#8217;s reasonable approval) in Landlord&#8217;s name, solely as and because Landlord is the fee simple owner of the Premises, as may be necessary for obtaining such permits, licenses
    and approvals, all without cost or liability to Landlord. Tenant shall operate in a first-class manner and shall not exceed the density limit for the Building under Applicable Laws. Tenant shall not commit waste or cause a public nuisance.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Compliance with Applicable Laws</u>. Tenant
    shall comply with all Applicable Laws and any agreements between Tenant and third parties with respect to the Premises and Tenant&#8217;s operation at the Premises. It is intended that the Tenant bear the sole risk of all present or future Applicable Laws,
    regulations and orders affecting the Premises, and the Landlord shall not be liable for their enforcement. Should there be any material noncompliance or alleged material noncompliance by Tenant with Applicable Laws or agreements between Tenant and
    third parties with respect to the Premises and Tenant&#8217;s operation at the Premises, Tenant shall promptly notify Landlord in writing of such actual or alleged noncompliance, which notice shall include (i) documentation that such actual or alleged
    noncompliance has been fully addressed and eliminated or, (ii) if such actual or alleged noncompliance has not been fully addressed and eliminated, a schedule to fully and expeditiously address and eliminate such actual or alleged noncompliance. The
    giving of such notice shall not relieve Tenant of any liability to Landlord or others for such actual or alleged noncompliance. To ensure Tenant&#8217;s compliance with Applicable Laws and Tenant&#8217;s performance of Tenant&#8217;s management, repair, maintenance, and
    compliance obligations hereunder, upon reasonable notice to Tenant and subject to and in accordance with Applicable Laws and reasonable confidentiality requirements pertaining to Tenant&#8217;s operations (provided such requirements do not impair or delay
    Landlord&#8217;s rights under this Section), Landlord may inspect or cause non-invasive independent third party inspections of the facility and Tenant&#8217;s operation to confirm compliance with Applicable Laws and Tenant&#8217;s management, repair, maintenance, and
    compliance obligations hereunder, at Landlord&#8217;s expense, except as otherwise provided in Section 3.3.7.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 3.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Hazardous Materials</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant, and any of Tenant&#8217;s assignees,
    sublessees, licensees, agents, servants, employees, invitees and contractors (or any of Tenant&#8217;s assignees, sublessees and/or licensees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Tenant Parties</b>&#8221;; any of
    them, a &#8220;<b>Tenant Party</b>&#8221;) (a) shall not, and shall not permit at any time, the handling, use, manufacture, release, storage, or disposal of Hazardous Materials in or about any portion of the Premises in violation of Applicable Laws, (b) shall
    always manage, handle, use, store, and dispose of such Hazardous Materials in a safe manner, according to prudent industry practice, and in compliance with Applicable Laws, and (c) shall at all times have any and all required permits, licenses and
    approvals required for or in connection with, the use and handling of Hazardous Materials at the Premises and at all times be in compliance with such required permits, licenses and approvals. &#8220;<b>Hazardous Materials</b>&#8221; means (a) any and all
    substances (whether solid, liquid or gas) defined, listed or otherwise classified or regulated as &#8220;biological compounds&#8221;, &#8220;bio-hazardous wastes&#8221;, &#8220;radiological elements&#8221;, &#8220;hazardous wastes,&#8221; &#8220;hazardous materials,&#8221; &#8220;hazardous substances,&#8221; &#8220;toxic
    substances,&#8221; &#8220;pollutants,&#8221; &#8220;contaminants,&#8221; &#8220;radioactive materials&#8221;, &#8220;toxic pollutants&#8221;, &#8220;solid wastes,&#8221; or other similar designations in, or otherwise subject to regulation under Environmental Laws, and (b) any other substances, constituents or wastes
    that are deemed to have a negative impact on human health or the environment, whether or not naturally occurring, or that are subject to Environmental Law, now or hereafter in effect, including but not limited to (A) petroleum, (B) refined petroleum
    products, (C) waste oil, (D) waste aviation or motor vehicle fuel and their byproducts, (E) asbestos, (F) lead in water, paint or elsewhere, (G) radon, (H) Polychlorinated Biphenyls (PCBs), (I) urea formaldehyde, (J) volatile organic compounds (VOC),
    (K) total petroleum hydrocarbons (TPH), (L) benzene derivative (BTEX), (M) poly- and perfluoroalkyl substances and other emerging contaminants, and (N) petroleum byproducts. Hazardous Materials further includes flammables, explosives, corrosive
    materials, radioactive materials, materials capable of emitting toxic fumes, hazardous wastes, toxic wastes or materials, and other similar substances, petroleum products and derivatives, and any substance subject to regulation by or under any
    Environmental Law. As between Landlord and Tenant, Tenant is deemed to be the operator of the Premises, the generator of any Hazardous Materials waste present at or generated at the Premises or as part of Tenant&#8217;s operations, and the owner of all
    Hazardous Materials at the Premises at any and all times during the Term. On or before the expiration or earlier termination of this Lease, Tenant shall remove from the Premises all Hazardous Materials introduced to the Premises by Tenant, any other
    Party or any other party other than Landlord during the Term of the Lease, regardless of whether such Hazardous Materials are included on the Hazardous Materials List or present at the Premises in concentrations which require removal under Applicable
    Laws. As used herein, the term &#8220;<b>Contamination</b>&#8221; means the presence of Hazardous Materials in the air, soil, surface and/or ground water in, on or under the Premises and/or any adjacent property at levels above those permitted by applicable
    Environmental Laws.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>Landlord acknowledges that it is not the intent
    of this <u>Section 3.3</u> to prohibit Tenant from using the Premises for the Permitted Use. Tenant may operate its business according to best industry practices so long as the use or presence of Hazardous Materials is strictly and properly monitored
    according to all then applicable Environmental Laws, all Hazardous Materials at the Premises are used in the operation of Tenant&#8217;s business, and such use is consistent with similar first-class facilities engaged in the Permitted Use in the greater San
    Diego County area. Notwithstanding the foregoing, Tenant shall have no right to install any underground storage tanks at the Premises unless Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s sole and
    absolute discretion. In conducting its research activities using Hazardous Materials, Tenant shall not perform work at or above the risk category Biosafety Level 3 as established by the Department of Health and Human Services publication Biosafety in
    Microbiological and Biomedical Laboratories (5th Edition) (as it may be or may have been further revised, the &#8220;<b>BMBL</b>&#8221;) or such nationally recognized new or replacement standards as Landlord may reasonable designate, without the prior written
    approval of Landlord, which approval shall not be unreasonably withheld, conditioned, or delayed (and if such change in Tenant&#8217;s operation requires the approval of Landlord&#8217;s lender, the lender&#8217;s denial of approval shall be deemed a reasonable basis
    for Landlord to deny its approval); provided, however, Landlord&#8217;s approval of any operation above the risk category Biosafety Level 3 shall be in Landlord&#8217;s sole discretion. Tenant shall comply with all applicable provisions of the standards of the
    BMBL to the extent applicable to Tenant&#8217;s operations in the Premises.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>As a material inducement to Landlord to allow
    Tenant to use Hazardous Materials in connection with its business, Tenant agrees to deliver to Landlord prior to the Commencement Date a list identifying each type of Hazardous Materials (other than ordinary office and cleaning supplies used in
    cleaning of the office spaces within the Building) to be brought upon, kept, used, stored, handled, treated, generated on, or released or disposed of from, the Premises and setting forth any and all governmental approvals or permits required in
    connection with the presence, use, storage, handling, treatment, generation, release or disposal of such Hazardous Materials on or from the Premises (&#8220;<b>Hazardous Materials List</b>&#8221;). Upon Landlord&#8217;s request (not more than once per year, unless
    Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>, a release or threatened release of Hazardous Materials has occurred, or in connection with a sale, financing, refinancing, or recapitalization of
    Landlord&#8217;s interest in the Premises), or any time that Tenant is required to deliver a Hazardous Materials List to any governmental authority (e.g., the fire department) or an insurer in connection with Tenant&#8217;s use or occupancy of the Premises, Tenant
    shall deliver to Landlord a copy of such Hazardous Materials List. Tenant shall deliver to Landlord true and correct copies of the following documents (the &#8220;<b>Haz Mat Documents</b>&#8221;) relating to the use, storage, handling, treatment, generation,
    release or disposal of Hazardous Materials prior to the Commencement Date, or if unavailable at that time, concurrent with the receipt from or submission to a governmental authority: permits; licenses, approvals; reports and correspondence; storage and
    management plans; notice of violations of any Applicable Laws; fire safety plans; spill response plans; plans relating to the installation of any storage tanks to be installed in or under the Premises (provided, said installation of tanks shall only be
    permitted after Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s sole and absolute discretion with respect to underground storage tanks); all closure plans or any other documents required by any and
    all governmental authorities for any storage tanks installed in, on or under the Premises for the closure of any such tanks; and a Surrender Plan (to the extent surrender in accordance with Section 3.3.9 cannot be accomplished in three (3) months).
    Tenant is not required, however, to provide Landlord with any portion(s) of the Haz Mat Documents containing proprietary information of a proprietary nature that, in and of themselves, do not contain a reference to any Hazardous Materials or hazardous
    activities. It is not the intent of this Section to provide Landlord with information that could be detrimental to Tenant&#8217;s business should such information become possessed by Tenant&#8217;s competitors.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except to the extent caused by the gross
    negligence or willful misconduct of, or breach of contract by, Landlord or Landlord Parties, Tenant releases Landlord and Landlord Parties from and agrees to indemnify, defend and hold Landlord and Landlord Parties harmless for, from and against any
    and all actions (including, without limitation, remedial or enforcement actions of any kind, administrative or judicial proceedings, and orders or judgments arising out of or resulting therefrom), costs, claims, damages (including, without limitation,
    punitive damages and damages based upon diminution in value of the Premises, or the loss of, or restriction on, use of the Premises), expenses (including, without limitation, legal, consultants&#8217; and experts&#8217; fees, court costs and amounts paid in
    settlement of any claims or actions), fines, forfeitures or other civil, administrative or criminal penalties, injunctive or other relief (whether or not based upon personal injury, property damage, or Contamination of, or adverse effects upon, the
    environment, water tables or natural resources), liabilities or losses (i) that arise prior to, during, or after the Term, as a result of the presence, suspected presence, release, or suspected release of any Hazardous Materials in or into the
    environment, including the air, soil, surface water, or groundwater at, on, about, under, emanating to or from, having emanated to or from, or within the Premises, or any portion thereof caused or exacerbated by, or otherwise attributable to, Tenant or
    any other party (other than Landlord or Landlord Parties) prior to the date that Tenant vacates the Premises in the condition required following the termination or earlier expiration of the Term, or (ii) that arise prior to, during, or after the Term,
    as a result of the breach by Tenant of any of its obligations under this Section 3.3, including in each case, without limitation, the cost of assessment, containment and/or removal of any such Hazardous Materials, the reasonable and necessary cost of
    any actions taken in response to a release of any such Hazardous Materials so that it does not migrate or otherwise cause or threaten danger to present or future public health, safety, welfare or the environment, and costs incurred to comply with
    Environmental Laws in connection with all or any portion of the Premises or the operation thereof (or any surrounding areas for which Tenant or Landlord has any legal liability or obligation) during the Term.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>EXCEPT AS OTHERWISE PROVIDED FOR HEREIN,
    LANDLORD LEASES AND WILL LEASE, AND TENANT TAKES AND WILL TAKE, THE PREMISES IN AN ENVIRONMENTALLY &#8220;AS IS&#8221; CONDITION, AND TENANT ACKNOWLEDGES THAT LANDLORD HAS NOT MADE AND WILL NOT MAKE, NOR SHALL LANDLORD BE DEEMED TO HAVE MADE, ANY WARRANTY OR
    REPRESENTATION, EXPRESS OR IMPLIED, WITH RESPECT TO THE ENVIRONMENTAL CONDITION OF THE PREMISES, INCLUDING ANY WARRANTY OR REPRESENTATION AS TO FITNESS OF THE PREMISES FOR ANY PARTICULAR USE OR PURPOSE, AS TO THE PRESENCE OR ABSENCE OF ANY HAZARDOUS
    MATERIALS, LATENT OR PATENT, ANY ENVIRONMENTAL CONDITION, KNOWN OR UNKNOWN, OR ANY AIR, SOIL, SOIL GAS, OR GROUNDWATER CONDITION, IT BEING AGREED THAT ALL RISKS AND LIABILITY INCIDENT TO ANY OF THE FOREGOING ARE TO BE BORNE BY TENANT</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant hereby represents and warrants to
    Landlord that (i) neither Tenant nor any of its legal predecessors has been required by any prior landlord, lender or governmental authority at any time to take remedial action in connection with Hazardous Materials contaminating the natural
    environment, which contamination was caused or permitted by Tenant or such predecessor or resulted from Tenant&#8217;s or such predecessor&#8217;s acts, omissions, or use or occupation of the property in question, and (ii) Tenant is not subject to any enforcement
    order issued, or regulatory proceedings or prosecution commenced, by any governmental authority in connection with the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials (including, without limitation, any order
    related to the failure to make a required reporting to any governmental authority).</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Upon prior notice and using reasonable efforts
    to coordinate with Tenant, Landlord shall have the right but not the obligation to conduct annual tests (or at any time Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>) of the Premises including, without
    limitation, intrusive tests of the subsurface soil and/or ground water, to determine whether any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation. Landlord shall pay the cost of such test of the Premises; provided,
    however, that if such tests show any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation, Tenant shall pay the cost of such test. In connection with such testing, upon the request of Landlord, Tenant shall deliver to
    Landlord or its consultant such non-proprietary information concerning the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials in or about the Premises by Tenant or any Tenant Party as Landlord may reasonably
    request. If Contamination has occurred for which Tenant is liable under this Section 3.3, Tenant shall pay all costs to conduct such tests. Tenant shall, at its sole cost and expense, promptly and satisfactorily remediate any Contamination identified
    by such testing in accordance with all Environmental Laws. Landlord&#8217;s receipt of or satisfaction with any environmental assessment in no way waives any rights that Landlord may have against Tenant.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Furthermore, upon the expiration of the Term
    or earlier termination of Tenant&#8217;s right of possession, Tenant shall surrender the Premises to Landlord free of Hazardous Materials brought upon, kept, used, stored, handled, treated, generated in, or released or disposed of from, the Premises by any
    person other than Landlord (collectively, &#8220;<b>Tenant&#8217;s Hazardous Materials</b>&#8221;) and released of any license, clearance or other authorization or requirement of any kind required to enter into and restore the Premises issued by any governmental
    authority having jurisdiction over the use, storage, handling, treatment, generation, release, disposal, removal or remediation of Hazardous Materials in, on or about the Premises (collectively referred to herein as &#8220;<b>Hazardous Materials Clearances</b>&#8221;).






    At least three (3) months prior to the surrender of the Premises or such earlier date as Tenant may elect to cease operations at the Premises, Tenant shall deliver to Landlord a narrative description of the actions proposed (or required by any
    governmental authority) to be taken by Tenant in order to surrender the Premises (including any Alterations permitted by Landlord to remain in the Premises) at the expiration or earlier termination of the Term, free from any residual impact from
    Tenant&#8217;s Hazardous Materials and otherwise released for unrestricted use and occupancy (the &#8220;<b>Surrender Plan</b>&#8221;). Such Surrender Plan shall be accompanied by a current listing of (i) all Hazardous Materials licenses and permits held by or on behalf
    of any Tenant Party with respect to the Premises, and (ii) all Hazardous Materials used, stored, handled, treated, generated, released or disposed of from the Premises, and shall be subject to the review and reasonable approval of Landlord&#8217;s
    environmental consultant. In connection with the review and approval of the Surrender Plan, upon the request of Landlord, Tenant shall deliver to Landlord or its consultant such additional non-proprietary information concerning Tenant&#8217;s Hazardous
    Materials as Landlord shall reasonably request. On or before such surrender, Tenant shall deliver to Landlord evidence that the approved Surrender Plan shall have been satisfactorily completed and Landlord shall have the right, subject to reimbursement
    at Tenant&#8217;s expense as set forth below, to cause Landlord&#8217;s environmental consultant to inspect the Premises and perform such additional procedures, including without limitation intrusive subsurface testing of soil and/or ground water, as may
    reasonably be deemed necessary to confirm that the Premises are, as of the effective date of such surrender or early termination of the Lease, free from any Tenant&#8217;s Hazardous Materials. Tenant shall reimburse Landlord, as Additional Rent, for the
    actual out-of- pocket expense incurred by Landlord for Landlord&#8217;s environmental consultant to review the Surrender Plan and to visit the Premises and verify satisfactory completion of the same, which cost shall not exceed $5,000 (which amount shall be
    increased by the same percentage as the Index as of each Adjustment Date). Landlord shall have the unrestricted right to deliver such Surrender Plan and any report by Landlord&#8217;s environmental consultant with respect to the surrender of the Premises to
    third parties on a need-to-know basis.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>If Tenant shall fail to prepare or submit a
    Surrender Plan approved by Landlord, or if Tenant shall fail to complete the approved Surrender Plan, or if such Surrender Plan, whether or not approved by Landlord, shall fail to adequately address any Tenant&#8217;s Hazardous Materials in, on or about the
    Premises, Landlord shall have the right to take such actions as Landlord may reasonably deem appropriate to assure that the Premises are surrendered free from any Tenant&#8217;s Hazardous Materials, the cost of which actions shall be reimbursed by Tenant as
    Additional Rent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.3.10<font style="font-family: Times New Roman, Times, Serif">&#160; &#160;&#160; </font>Tenant&#8217;s obligations under this Section 3.3
    shall survive the expiration or earlier termination of the Lease. During any period of time after the expiration or earlier termination of this Lease required by Tenant or Landlord to complete the removal from the Premises of any Hazardous Materials
    (including, without limitation, the release and termination of any licenses or permits restricting the use of the Premises and the completion of the approved Surrender Plan), Tenant shall continue to pay the full Rent in accordance with this Lease for
    any portion of the Premises not relet by Landlord in Landlord&#8217;s sole discretion, which Rent shall be prorated daily.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 3.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Alterations</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Consent</u>. Tenant may make any alterations,
    improvements, additions or changes to the Premises, including, without limitation, the Tenant Improvements as defined in the Work Letter, (collectively &#8220;<b>Alterations</b>&#8221;) that meet all of the following criteria without first obtaining Landlord&#8217;s
    Consent: (a) the Alterations are cosmetic, (b) the Alterations are non-structural and do not affect the mechanical systems of the Building, (c) the Alterations cost less than $1,000,000.00 per project (which amount shall be increased by the same
    percentage as the Index as of each Adjustment Date); and (d) after the Alterations, the Premises will continue to be used for the Permitted Use (collectively, Alterations meeting the criteria of (a)-(d), &#8220;Minor Alterations&#8221;). Any Alterations that are
    not Minor Alterations shall be subject to Landlord&#8217;s approval, such approval not to be unreasonably withheld, conditioned or delayed. Tenant shall reimburse Landlord for any third-party expenses reasonably incurred by Landlord in connection with the
    review, inspection, and coordination of Tenant&#8217;s plans for Alterations and Tenant&#8217;s performance thereof. Tenant hereby agrees to provide copies of all plans of such Alterations, regardless of whether Landlord&#8217;s consent is required. Tenant shall
    diligently and expeditiously complete any Alterations commenced. All Alterations shall become part of the realty constituting the Premises and shall belong to Landlord and shall not be removed by Tenant. If any Alteration is anticipated to cost more
    than $1,500,000, Landlord shall have the right to require Tenant to post a performance or payment bond in connection with any work or service done or purportedly done by or for the benefit of Tenant. Tenant acknowledges and agrees that all such work or
    service is being performed for the sole benefit of Tenant and not for the benefit of Landlord. Landlord shall, at the time it provides its approval for a proposed Alteration, advise Tenant whether the Alteration, or any portion thereof, is a Required
    Removable, as defined in Section 4.2.2. For the avoidance of doubt, with respect to the Tenant Improvements only, in the event of any conflict between the terms of this Section 3.4 and the terms of the Work Letter, the terms of the Work Letter shall
    control.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Liens</u>. With respect to any Alterations,
    Tenant hereby agrees as follows: (a) Tenant shall not cause or permit any construction, mechanics&#8217; or other liens or encumbrances to be placed upon the Premises, or Tenant&#8217;s leasehold interest hereunder, whether in connection with any work or service
    done or purportedly done by or for the benefit of Tenant, its subtenants, or any other party acting under or through Tenant, or otherwise, (b) Tenant shall cause all Alterations to be constructed free of all liens, in accordance with all Applicable
    Laws and shall, upon Landlord&#8217;s request, deliver lien waivers to Landlord in the form required by Applicable Law, (c) Tenant shall pay the costs of the Alterations and so that Landlord, the Premises will be protected against any loss from any
    mechanic&#8217;s, materialmen&#8217;s, or other liens, and (d) prior to the commencement of the construction of any Alterations, Tenant shall give to Landlord evidence of the insurance required by <u>Section 6.2.4</u>. Notwithstanding the foregoing or anything to
    the contrary in this Lease, Tenant may contest any lien if (i) such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord of such dispute, and (iii) such lien is fully
    bonded by Tenant to the reasonable satisfaction of Landlord and any Mortgagee. Tenant shall give Landlord notice at least fifteen (15) days prior to the commencement of any work in the Premises, other than any Alterations that are purely cosmetic.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requirements</u>. Prior to starting work on
    any Alterations, Tenant shall furnish Landlord with two (2) complete sets of professionally prepared working drawings (which shall include any architectural, structural, electrical, mechanical, computer system wiring, and telecommunication plans, which
    shall all be in CAD or other electronic format if requested by Landlord), and will be consistent with the construction methods and procedures manual attached hereto as Exhibit I, as amended from time to time for the Premises (the &#8220;<b>Tenant
      Construction Manual</b>&#8221;); names of contractors reasonably acceptable to Landlord; required permits and approvals; and evidence of contractor&#8217;s and subcontractor&#8217;s insurance in amounts reasonably required by Landlord and naming as additional insureds
    the Landlord, the managing agent for the Premises, and such other Additional Insured Parties (as defined in Section 13) as Landlord may designate for such purposes. All Cable shall be clearly marked with adhesive plastic labels (or plastic tags
    attached to such Cable with wire) to show the purpose of such Cable (i) every six (6) feet in locations behind walls, beneath floors, and above ceilings (specifically including, but not limited to, the electrical room risers), and (ii) at the
    termination point(s) of such Cable. &#8220;<b>Cable</b>&#8221; shall mean and refer to any electronic, fiber, phone and data cabling and related equipment that is installed by or for the exclusive benefit of Tenant or any party acting under or through Tenant. Any
    changes to the plans and specifications, other than di minimus changes that are purely cosmetic, do not affect the Building structure or mechanical systems, and do not cause the cost of the Alterations to exceed $1,000,000 (which amount shall be
    increased by the same percentage as the Index as of each Adjustment Date), must also be submitted to Landlord for its approval. Prior to commencing Alterations, Tenant shall provide Landlord with a copy of the contract for the Alterations and evidence
    satisfactory to Landlord as to the existence of all necessary permits (to the extent not previously provided). Alterations shall be (a) constructed in a good and workmanlike manner, (b) consistent with first class standards, (c) consist of materials of
    a quality reasonably approved by Landlord, and Tenant shall ensure that no Alteration impairs any Building system, (d) performed by contractors or mechanics whose labor union affiliations are not incompatible with those of any workers, contractors or
    subcontractors who may be employed, retained or engaged by the Landlord for the development and making of any alterations at the Premises, and who are otherwise reasonably approved by Landlord, (e) in accordance with the Tenant Construction Manual, if
    any, and (f) designed and performed in accordance with all applicable Laws. It shall be deemed reasonable for Landlord to withhold its consent to any Alteration that adversely affects a Building&#8217;s roof, structure, or systems, that is inconsistent with
    a first-class life science building, that results in an increase in gross floor area at the Premises or alteration of any Building footprint, that would violate any certificate of occupancy for the Building or any other permits or licenses relating to
    the Building, that would reduce the utility of the Premises for life sciences laboratory, research, and manufacturing purposes, or that is otherwise inconsistent with the requirements of this Section. Tenant shall reimburse Landlord for any third-party
    expenses incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s plans for Alterations and Tenant&#8217;s performance thereof. Upon completion, Tenant shall furnish &#8220;as-built&#8221; plans (in CAD or other electronic format, if
    requested by Landlord) for Alterations, customary American Institute of Architects completion affidavits, full and final waivers of lien, any applicable certificate of occupancy for the space affected by such Alterations and other applicable municipal
    or local sign-offs and inspection reports, and any other items reasonably required by Landlord for closing out the particular work in question. Landlord&#8217;s approval of an Alteration shall not be deemed to be a representation by Landlord that the
    Alteration complies with Law or will not adversely affect any Building system.&#160;</p>
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Construction Oversight Fee</u>. With respect
    to any Alterations requiring Landlord&#8217;s consent under Section 3.4.1, Tenant shall pay Landlord a construction oversight fee (&#8220;<b>Construction Oversight Fee</b>&#8221;) equal to the sum of one percent (1%) of total hard and soft project costs, provided that
    Landlord&#8217;s obligations in connection with the Alterations are limited to oversight only and not direct management of the project. The Construction Oversight Fee shall be calculated based on hard and soft project costs for the Alterations that were
    approved by Landlord for the portion of work that has been performed and invoiced and shall be payable monthly in arrears concurrent with the approved hard and soft project costs for the Alterations during the applicable month.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Completion</u>. Upon the completion of any
    Alterations, Tenant shall, to the extent applicable, promptly give to Landlord (a) a reproducible copy of the &#8220;as-built&#8221; drawings of such Alterations, (b) a certificate of completion executed on behalf of Tenant&#8217;s architect and/or engineering
    certifying completion of such Alterations in accordance with the respective plans and specifications, (c) a copy of the certificate of occupancy issued by the applicable governmental authorities with respect to such Alterations, and (d) copies of any
    warranties or guarantees with respect to such Alterations (and ensure that such warranties or guarantees are assignable to Landlord and/or run to both Landlord and Tenant&#8217;s benefit).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">3.4.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Ownership of Alterations</u>. Any Alterations
    shall belong to Tenant until the Termination Date, at which time the Alterations (other than Tenant&#8217;s Trade Fixtures (as hereinafter defined)) shall belong to Landlord; provided, however, in no event shall the Alterations be removed by Tenant prior to
    the Termination Date, except as expressly provided herein. For purposes of this Lease, &#8220;<b>Trade Fixtures</b>&#8221; shall mean a piece of equipment placed on the Premises owned by Tenant and used in Tenant&#8217;s trade or business. For the avoidance of doubt,
    Trade Fixtures shall not include, without limitation, Building systems and machinery, built-in cabinet work and/or lab benches, purpose-built mezzanine space, all HVAC, air handling, electrical, mechanical and plumbing equipment and related ducts,
    shafts, and conduits, all exterior venting fume hoods, walk-in freezers and refrigerators, clean-rooms, climatized rooms, electrical panels and power back-up distribution systems. The parties agree that Landlord will be treated for all purposes,
    including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other cost recovery deductions for federal tax purposes with respect to) any improvements, equipment, or personal property that were paid for, or
    reimbursed by, Landlord, including any allowance provided by Landlord, and Tenant will be treated for all purposes, including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other cost recovery deductions for
    federal tax purposes with respect to) any improvements to the extent that the cost for such improvements were paid for by Tenant and to the extent any such costs exceed any allowance provided by Landlord. Unless required to adopt a contrary position as
    a result of an administrative or judicial proceeding, the parties shall take no action inconsistent with, the intentions set forth in this paragraph. The parties will provide each other with such cooperation as is reasonably necessary to implement the
    intentions of this paragraph.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Jeopardy of Insurance</u>. Tenant shall
    neither do nor omit to do anything that might result in the actual or threatened reduction or cancellation of or material adverse change in insurance carried by Landlord or Tenant on the Premises. If any such insurance is actually, or threatened to be,
    cancelled, reduced or materially adversely changed by an insurer as a result of the use or occupancy of the Premises or any article kept in or about the Premises or any act or omission of Tenant or any person for whom Tenant is in law responsible or
    any occupant of the Premises, and if Tenant fails to remedy the condition or the use or occupancy giving rise to such actual or threatened cancellation, reduction or change within three (3) business days after notice thereof, Landlord may, without
    limiting its other remedies for the default, enter upon the Premises and remedy the condition, use or occupancy giving rise to such actual or threatened cancellation, reduction or change, and Tenant shall pay to Landlord its cost of doing so within ten
    (10) days following invoice, plus an administrative fee equal to ten percent (10%) of such cost. Landlord shall not be liable for any damage to either the Premises or any property located on the Premises as a result of such entry.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Dogs</u>. Tenant shall be permitted to bring
    a reasonable number of non-aggressive, fully domesticated, properly licensed, fully vaccinated, and well behaved dogs, kept by Tenant&#8217;s employees as pets, into the Premises, provided and upon condition that: (a) all dogs shall be strictly controlled at
    all times, (b) dogs shall not be permitted to foul, damage or otherwise mar any part of the Building or Premises; and (c) while entering and exiting the Premises, all dogs shall be kept on leashes. Landlord may limit the number, weight, and breed of
    dogs that may be permitted in the Premises, and Landlord may implement other rules and regulations not inconsistent with this Section 3.6 that Landlord, in its sole discretion, deems reasonable or prudent. Tenant shall be responsible for any damage and
    additional cleaning costs and all other costs which may arise from the dogs&#8217; presence in the Building and on the Premises. Tenant shall be liable for, and hereby agrees to indemnify, defend and hold Landlord harmless from any and all claims arising
    from any and all acts (including but not limited to biting and causing bodily injury to, or damage to the property of, another lessee, sublessee, occupant, licensee, invitee, Landlord or an employee of Landlord) of, or the presence of, any dog in or
    about the Premises or the Building. Tenant shall promptly remove any dog waste and excrement from the Premises and Building. Dogs shall be strictly controlled and supervised at all times (including, without limitation, by being on leashes) by Tenant&#8217;s
    employees, with no less than one (1) such employee responsible for so controlling and supervising no more than two (2) dogs apiece. Within three (3) business days following Landlord&#8217;s request therefor, Tenant shall provide Landlord with reasonably
    satisfactory evidence showing that all current vaccinations have been received by any dogs permitted on the Premises. No dog shall be brought to the Premises if such dog is ill or contracts a disease that could potentially threaten the health or
    wellbeing of any person on the Premises (which diseases may include, without limitation, rabies, leptospirosis and lyme disease). Tenant shall not permit any objectionable dog related noises or odors to emanate from the Premises (as determined by
    Landlord in its sole discretion), and in no event shall any dog be at the Premises overnight or for any extended period of time. Tenant shall install and maintain dog waste bag dispensers in outdoor areas of the Premises, and all waste generated by any
    dogs in or about the Premises shall be promptly removed and disposed of (on no less than a daily basis) in trash receptacles. Any areas of the Premises affected by such waste shall be immediately cleaned and otherwise sanitized. Landlord may require
    Tenant to permanently ban any dog from the Premises if (i) any such dog exhibits aggressive behavior, damages or destroys property in the Premises, violates specific provisions of this Section, defecates or urinates in any non-outdoor area of the
    Project, or defecates in any outdoor area of the Project and Tenant fails to remove such waste in accordance with the terms of this Section, and (ii) any such dog is found by Landlord in its sole but good faith discretion to be a substantial, repeated
    nuisance to the Premises, and, in any such event, such substantial, repeated nuisance persists after at least two (2) written notices to Tenant from Landlord in any twelve (12) month period), then Landlord may terminate Tenant&#8217;s rights under this
    Section. Tenant shall promptly pay to Landlord, within thirty (30) days after demand, all costs incurred by Landlord that directly result from the presence of any of dogs in the Premises. Tenant&#8217;s right provided in this Section is personal only to the
    original named Tenant and/or any Permitted Transferee, shall not be exercisable by any other assignee, subtenant or other transferee of or successor to any portion of Tenant&#8217;s interest under the Lease or to the Premises.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">3.7<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;&#160;&#160;&#160;&#160;</font><u>LEED Standards</u>. Landlord and Tenant each
    acknowledge that the Building has been designed to meet the standard for at least a &#8220;Gold&#8221; rating under the U.S. Green Building Council&#8217;s Leadership in Energy and Environmental Design (&#8220;<b>LEED</b>&#8221;) rating system. Tenant shall reasonably cooperate
    with Landlord to obtain and maintain LEED Gold certification for the Building, including, without limitation, cooperating with Landlord in its submission of all filings and applications for LEED Gold certification, at Tenant&#8217;s cost and expense. All
    Alterations, and any lighting installed by Tenant in the Premises, shall be designed, maintained, and installed in accordance with the requirements for at least LEED Gold, as the same may change from time to time. If necessary to ensure compliance with
    LEED Gold or such other standards, Tenant further agrees to engage a qualified third party LEED or Green Globe Accredited Professional or similarly qualified professional during the design phase of any Alterations, in order to review all plans,
    material procurement, demolition, construction and waste management procedures to ensure they are in full conformance with the requirements to maintain a LEED Gold or such other rating.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 4&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>REPAIR AND MAINTENANCE; SERVICES</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">4.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;</font><u>Tenant Repair and Maintenance Obligations</u>.
    The parties intend for this Lease to be absolutely triple net. Tenant shall be responsible for all repairs, replacements and maintenance of the Premises. Landlord shall have no obligation whatsoever to repair or maintain the Premises. Tenant shall
    repair and maintain the Premises in substantially the condition as exists as of the Commencement Date of this Lease (and as it may be improved or altered thereafter, including, without limitation, pursuant to the Work Letter), keep same in good order,
    condition and repair, and in compliance with Applicable Laws, ordinary wear and tear and casualty excepted, to the extent Tenant is not otherwise obligated to restore the same.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 4.2&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;<u>Condition of Premises on Surrender</u></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">4.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except as otherwise provided in this <u>Section
      4.2</u>, upon the Termination Date, all Alterations (other than Tenant&#8217;s Trade Fixtures) shall belong to Landlord without compensation, and title shall pass to Landlord under this Lease. On the Termination Date, Tenant shall give Landlord possession
    of the Premises, together with all such Alterations (other than Tenant&#8217;s Trade Fixtures), in the good, broom clean condition, free of all debris, excepting only ordinary wear and tear and damage that Tenant is not required to repair or restore under
    this Lease. On or prior to the Termination Date, Tenant shall also (a) remove all of Tenant&#8217;s furniture, Trade Fixtures, furnishings, equipment belonging to the Tenant, and other personal property (collectively, the &#8220;<b>Personalty</b>&#8221;), and (b) repair
    any damage caused by the removal of such Personalty. All of Tenant&#8217;s Personalty not so removed by Tenant, may be removed from the Premises by Landlord and stored, at Tenant&#8217;s sole risk and expense, and in any event, Landlord shall not be responsible
    for the value, preservation, or safekeeping thereof. Tenant shall pay to Landlord, upon demand, all reasonable expenses so incurred by Landlord, including the cost of repairing any damage caused by removal and storing such Personalty (collectively, &#8220;<b>Tenant&#8217;s






      Property</b>&#8221;). Any such Tenant&#8217;s Property not claimed by Tenant within sixty (60) days after Tenant&#8217;s surrender of the Premises shall, at Landlord&#8217;s option, be deemed either abandoned or conveyed by Tenant to Landlord under this Lease without
    further payment or credit by Landlord to Tenant. On the Termination Date, Tenant shall assign to Landlord all manufacturers&#8217; and contractors&#8217; warranties with respect to the Premises and the Alterations (including all fixtures therein or thereon but
    excluding Tenant&#8217;s Trade Fixtures) and Tenant shall use commercially reasonable efforts obtain the consent of the issuers of such warranties (which may include, without limitation, the payment of an assignment fee), to the extent that such consent is
    required for the assignment to Landlord.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">4.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord, at the time required by <u>Section
      3.4.1</u>, by written notice to Tenant may require Tenant, at Tenant&#8217;s expense, to remove any Alterations or other affixed installations that, in Landlord&#8217;s reasonable judgment, are of a nature that are not customary office or life science
    improvements and would require removal and repair costs that are materially in excess of the removal and repair costs associated with standard improvements for the Permitted Use (&#8220;<b>Required Removables</b>&#8221;). Required Removables shall include, without
    limitation, internal stairways, raised floors, vaults, rolling file systems, structural alterations and modifications (including any slab penetrations) other than de minimis alterations and modifications associated with connection of other improvements
    to the structure of the Building or relocation of demising walls provided that the same are otherwise consistent with first class life science buildings, Tenant&#8217;s signage, supplemental systems (including HVAC), vivariums, and any Cable installed by or
    on behalf of Tenant that is not necessary for the proper functioning of any Alterations remaining in the Premises in accordance with this Lease. Notwithstanding the foregoing, any fixtures or improvements existing within the Premises on the Effective
    Date shall not be deemed Required Removables. The Required Removables shall be removed by Tenant before the expiration or earlier termination of this Lease in accordance with Section this Section 4.2, unless otherwise directed by Landlord. Landlord
    shall be treated as the owner of all Alterations (but, subject to Section 4.2.1, not any of Tenant&#8217;s Property, including any trade fixtures and equipment that are installed in a manner that will not damage the Premises when removed) during the term of
    the Lease, including for tax and depreciation purposes, but Tenant shall have the exclusive right to use the same subject to the terms of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">4.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Services and Utilities</u>. Landlord shall
    not be obligated to furnish to the Premises any services or utilities (including, without limitation, janitorial services), and Tenant shall contract directly with the providers of all services and utilities Tenant desires to receive at the Premises,
    at Tenant&#8217;s sole cost and expense. Tenant shall have the right to add alternative electricity sources such as additional solar panels, the installation of which shall be subject to Section 3.4. Landlord is not responsible for the furnishing of, or any
    interruption, diminishment or termination of, services or utilities, whether due to the application of Laws, the failure of any equipment, the performance of maintenance, repairs, improvements or alterations, or utility interruptions, and no such
    interruption, diminishment, or termination shall render Landlord liable to Tenant, give rise to an abatement of Rent, or relieve Tenant from the obligation to fulfill any covenant or agreement. Except as expressly set forth in Article 9, below,
    Landlord shall in no event be required under any provision of this Lease or applicable Law to maintain or repair or to make any alterations, rebuildings, replacements, changes, additions or improvements on or off the Premises during the Term of this
    Lease. Tenant acknowledges that it shall be responsible for providing and procuring all other services necessary to its operations in and on the Premises. If Tenant (or any party claiming by, through or under Tenant) pays directly to the provider for
    any energy consumed at the Building, Tenant, promptly upon request, shall deliver to Landlord (or, at Landlord&#8217;s option, execute and deliver to Landlord an instrument enabling Landlord to obtain from such provider) any data about consumption that
    Landlord, in its reasonable judgment, is required to disclose to a prospective buyer, tenant or mortgage lender under California Public Resources Code &#167;25402.10 or any similar law. Further, Tenant hereby waives and releases its right to make repairs at
    Landlord&#8217;s expense under Sections 1932(1), 1933(4), 1941 and 1942 of the California Civil Code or any similar or successor laws now or hereinafter in effect. At Landlord&#8217;s request, Tenant shall provide Landlord information regarding Tenant&#8217;s energy
    usage at the Premises from time to time (provided that Landlord shall hold such information confidential to the extent Landlord is not required to disclose such information pursuant to Applicable Law, nothing in this sentence being deemed to prohibit
    Landlord from utilizing such information to make public statements about the sustainability profile or &#8220;green&#8221; nature of Landlord, or Landlord&#8217;s affiliates, properties).&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in"></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 5</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ASSIGNMENT AND SUBLETTING</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 5.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>General Prohibition on Transfers</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.1.1&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Transfers Generally</u>. Tenant shall not,
    directly or indirectly, make a Transfer (as defined below), without Landlord&#8217;s consent, except as expressly set forth in this <u>Article 5</u>, and any purported Transfer that does not comply with the provisions of this <u>Article 5</u> shall, at
    Landlord&#8217;s option, be deemed an Event of Default by Tenant and shall be voidable by Landlord. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or successor laws, now or hereinafter in effect, and all
    other remedies, including any right at law or equity to terminate this Lease in connection with Landlord&#8217;s withholding its consent to any Transfer, on its own behalf and on behalf of the proposed transferee. Landlord shall not unreasonably withhold,
    condition, or delay its consent to an assignment of this Lease or any sublet of the Premises, subject to the terms and conditions of this Article 5. Without limitation, it is agreed that Landlord&#8217;s consent shall not be considered unreasonably withheld
    if the proposed Transferee (defined below) (a) is a governmental entity, (b) is incompatible with the character of occupancy of a first class life sciences building, (c) is an entity with which the payment for the sublease or assignment is determined
    in whole or in part based upon its net income or profits, (d) would subject the Premises to a use that would: (i) involve increased personnel or wear upon the Building in a manner inconsistent with first-class life science buildings; (ii) require any
    addition to or material modification of the Premises or the Building in order to comply with building code or other governmental requirements; or (iii) involve a violation of the Permitted Use clauses of this Lease, or (e) if there is any other
    reasonable ground not stated above for withholding consent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>&#8220;<b>Clients and Business
      Partners</b>&#8221; means persons or entities who are not employees or agents of Tenant or its Affiliates but are occupying or using portions of the Premises and are either (i) performing services for Tenant as subcontractors under Tenant&#8217;s contracts, (ii)
    personnel employed by persons or entities for whom Tenant is performing services on a contractual basis, or (iii) personnel employed by persons or entities with whom Tenant is engaged in a joint venture or joint teaming effort.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"> <br>
  </p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>&#8220;<b>Office Sharing</b>&#8221;
    means the use of portions of the Premises by Clients and Business Partners, if, with respect to such Clients and Business Partners, such use is in connection with the services being provided to Tenant by the applicable Clients and Business Partners,
    the services being provided to the applicable Clients and Business Partners by Tenant, or the services being jointly provided by Tenant and the applicable Clients and Business Partners.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>&#8220;<b>Transfer</b>&#8221; means any
    assignment, pledge, mortgage, charge, debenture (floating or otherwise), hypothecation, encumbrance, lien attaching to, collateral assignment, or other transfer of this Lease or the leasehold created hereby, or any sublet or other transfer of any
    portion of the Premises, or any Interest Transfer (as defined below), in any case whether voluntarily, by operation of law, or otherwise, or permitting the Premises to be used or occupied by anyone other than Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"> <font style="font-family: Times New Roman, Times, Serif">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font> &#8220;<b>Transferee</b>&#8221;
    means the party to which a Transfer is made.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>&#8220;<b>Interest Transfer</b>&#8221;
    means if Tenant is a corporation, trust, partnership, limited liability company or other entity, (i) the transfer of a Controlling Interest or a majority of the voting stock, beneficial interest, partnership interests, membership interests or other
    ownership interests therein (whether at one time or in the aggregate) or (ii) the sale, mortgage, hypothecation, or pledge of more than 50% of Tenant&#8217;s net assets. A &#8220;<b>Controlling Interest</b>&#8221; means the effective control over the management of such
    entity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.1.2&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Consent Requests</u>. If Tenant desires to
    effect a Transfer and such Transfer requires Landlord&#8217;s consent, then Tenant shall give to Landlord Notice thereof at least thirty (30) days, but not more than sixty (60) days, prior to the proposed effective date of the Transfer, which Notice shall
    include (a) the name and address of the proposed Transferee, (b) the relevant terms of the Transfer, (c) copies of financial reports and other relevant financial information for the proposed Transferee, (d) information regarding the nature of the
    business the proposed Transferee intends to operate in the Premises and how long the proposed Transferee has operated such business, (e) a fully executed copy of the proposed assignment, sublease, or other document to be used to effect the Transfer
    (the &#8220;<b>Transfer Document</b>&#8221;), and (f) payment to Landlord of One Thousand and No/100 Dollars ($1,000.00) as a transfer review fee. In addition, Tenant shall reimburse Landlord for any third-party expenses reasonably incurred by Landlord in
    connection with the review, inspection, and coordination of Tenant&#8217;s request for Landlord&#8217;s consent to a Transfer, not to exceed $5,000 per request (which amount shall be increased by the same percentage as the Index as of each Adjustment Date).
    Landlord shall not unreasonably withhold, condition or delay its consent to a Transfer. If Landlord&#8217;s consent is required with respect to a Transfer, and Landlord fails to respond to Tenant&#8217;s request for consent within thirty (30) days of Tenant&#8217;s
    request and submission of the documents required by this Section 5.1.2, Tenant may send a second written request, which request shall contain, in bold, capital letters, the following: &#8220;THIS NOTICE CONSTITUTES TENANT&#8217;S SECOND NOTICE OF ITS REQUEST FOR
    CONSENT TO A TRANSFER PURSUANT TO SECTION 5.1.2 OF THE LEASE; LANDLORD&#8217;S FAILURE TO RESPOND TO THIS NOTICE WITHIN FIVE (5) BUSINESS DAYS SHALL BE DEEMED LANDLORD&#8217;S CONSENT TO THE REQUESTED TRANSFER.&#8221; If Landlord fails to respond to such second notice
    within five (5) business days of receipt, Tenant&#8217;s request for the applicable Transfer shall be deemed approved. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or successor laws, now or hereinafter
    in effect, and all other remedies, including, without limitation, any right at law or in equity to terminate this Lease, on its own behalf and, to the extent permitted under all Applicable Laws, on behalf of the proposed transferee.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Permitted Transfer</u>. Notwithstanding
    anything in this <u>Article 5</u> to the contrary, Tenant may assign its interest in this Lease or sublease all or any part of the Premises (each a &#8220;<b>Permitted Transfer</b>&#8221;) to a Permitted Transferee (defined below) with notice to Landlord
    (delivered prior to the Transfer, or in the event Tenant is prohibited from doing so by Applicable Laws or contractual obligations, then as soon as reasonably practical) but without Landlord&#8217;s prior written consent; provided, that (i) with respect to a
    Permitted Transfer involving an assignment of this Lease, the Permitted Transferee assumes this Lease by a written assumption agreement delivered to Landlord prior to the effective date of such Permitted Transfer (unless such prior delivery is
    prohibited by Applicable Laws, in which event Tenant shall deliver such assumption agreement as soon as allowed), (ii) the Permitted Transferee shall use the Premises only for the Permitted Use, (iii) the use of the Premises by the Permitted Transferee
    shall not violate any other agreements or leases affecting the Property, (iv) the occurrence of a Permitted Transfer shall not waive Landlord&#8217;s rights as to any subsequent Transfer, (v) the Permitted Transferee shall satisfy the Credit Requirement
    (defined below), and (vi) Tenant shall have given Landlord written notice at least thirty (30) day before such Transfer (unless such notice is prohibited by applicable Law, in which event Tenant shall give such notice within ten days following such
    Transfer). As used herein, (A) &#8220;<b>Affiliate</b>&#8221; means any person or entity who or which controls, is controlled by, or is under common control with Tenant, (ii) a corporation or other entity which shall be a wholly owned subsidiary of the Tenant,
    (iii) the parent corporation or other entity that wholly owns Tenant, or (iv) a subsidiary of such parent corporation or other entity that wholly owns Tenant, or a corporation or other entity having a majority of its ownership in common with the
    ownership of Tenant, or (v) a Successor corporation, limited liability company or other entity; (B) &#8220;<b>Successor</b>&#8221; means any (i) business entity in which or with which Tenant is merged or consolidated in accordance with applicable statutory
    provisions governing merger and consolidation of business entities, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor, or (ii) the successor or surviving corporation or other entity in the event of a merger or consolidation
    of the Tenant with another corporation, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor; (C) &#8220;<b>Purchaser</b>&#8221; means any person or entity who or which acquires all or substantially all of the assets or equity interests of
    Tenant; (D) &#8220;<b>Permitted Transferee</b>&#8221; means an Affiliate, Successor or Purchaser. The &#8220;<b>Credit Requirement</b>&#8221; shall be deemed satisfied if, as of the effective date of the Permitted Transfer, the resulting tenant under this Lease meets or
    exceeds all of following minimum criteria immediately following the Transfer: (i) cash on hand equal to at least Two Billion Dollars ($2,000,000,000) according to the Permitted Transferee&#8217;s most recent financial statement, determined in accordance with
    generally accepted accounting principles (&#8220;<b>GAAP</b>&#8221;), (ii) outstanding debt of not more than sixty (60%) of the Permitted Transferee&#8217;s available cash on hand (as determined pursuant to the foregoing subsection (i) according to the Permitted
    Transferee&#8217;s most recent financial statement, determined in accordance with GAAP, and (iii) a market capitalization equal to at least Five Billion Three Hundred Million Dollars ($5,300,000,000).&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> </p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">5.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Other Permitted Transfers</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Office Sharing</u>. Notwithstanding anything
    in this <u>Article 5</u> to the contrary, provided no Event of Default has occurred and is continuing, Tenant may, without Landlord&#8217;s consent but upon at least ten (10) days&#8217; prior notice to Landlord, permit up to ten percent (10%) of the total
    leasable area of the Premises to be used for Office Sharing by Clients and Business Partners, without the same constituting a Transfer. Tenant agrees to notify Landlord, promptly upon Landlord&#8217;s written request therefor, as to the approximate amount of
    Office Sharing by Clients and Business Partners and to certify to Landlord that such use or occupancy constitutes Office Sharing by Clients and Business Partners and does not constitute a sublease, assignment or other leasehold interest.
    Notwithstanding the foregoing, Tenant shall not have the right to engage in Office Sharing with respect to any particular Clients and Business Partners as aforesaid if such Clients and Business Partners are engaged in a business, or the Premises will
    be used in a manner, that is inconsistent with the Permitted Use. For purposes of this Lease, the acts or omissions of the employees or other personnel of Clients and Business Partners shall be deemed to be the acts or omissions (as applicable) of
    Tenant. Upon Landlord&#8217;s request, Clients and Business Partners who are Office Sharing shall provide to Landlord satisfactory evidence of insurance covering their activities within the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">5.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;</font><u>Non-Transfers</u>. For so long as Tenant is
    a corporation whose ownership equity is available through the free trade of shares of stock on nationally recognized stock exchanges or over-the-counter (OTC) markets that are subject to the oversight of the United States Securities and Exchange
    Commission (a &#8220;<b>Public Company</b>&#8221;), any transfer of Tenant&#8217;s equity interests (or those of its Affiliates) whatsoever shall not be deemed a Transfer under this Lease and, for the avoidance of doubt, shall not require Landlord&#8217;s consent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">5.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;&#160;</font><u>Conditions to Effectiveness</u>. As
    conditions precedent to any Transfer becoming effective and binding on Landlord:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>except as otherwise specified herein, prior to
    the proposed effective date of the Transfer, Tenant shall give to Landlord a copy of the fully executed Transfer Document, which shall (i) be in form and substance reasonably acceptable to Landlord, and (ii) for an assignment of this Lease, contain
    Transferee&#8217;s express assumption of Tenant&#8217;s obligations under this Lease and waivers by Tenant, for the benefit of Landlord, of all applicable suretyship defenses (unless such prior delivery is prohibited by Applicable Laws, in which event Tenant shall
    deliver such documents as soon as allowed); and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.4.2 </font>as of the proposed effective date of the Transfer,
    there shall exist no Event of Default.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 5.5&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160; <u>Miscellaneous</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Notwithstanding any Transfer, permitted or
    otherwise, including without limitation a Permitted Transfer, (a) Tenant shall not be released and shall at all times remain directly, primarily, and fully responsible and liable for the payment of Rent and for compliance with all of the other
    obligations to be performed by Tenant under the terms, provisions and covenants of this Lease, and (b) if any Transferee defaults under this Lease, then Landlord may proceed directly against Tenant without the necessity of exhausting remedies against
    such Transferee. Notwithstanding the foregoing, Tenant shall be automatically released from all liability under the Lease accruing from and after the date of a Transfer if the Transfer is a Permitted Transfer that is a merger or consolidation whereby
    the named Tenant herein is not the surviving entity; provided, however, as conditions of the foregoing release: (i) the surviving entity shall assume, either expressly or by operation of law, all of the obligations of the preceding entity for
    liabilities accruing before and after the Transfer, and (ii) the surviving entity must retain ownership of substantially all of the assets of the preceding entity.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">27</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Upon the occurrence of an Event of Default, if
    all or any portion of the Premises is then subject to one or more subleases, then Landlord, in addition to any other remedies provided in this Lease or at law or in equity, may collect directly from the subtenants under such subleases all rents due and
    becoming due to Tenant or a Transferee under such subleases and apply such rent against any sums due to Landlord from Tenant under this Lease, and no such collection shall be construed to constitute a novation or release of Tenant from the further
    performance of Tenant&#8217;s obligations under this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except for any Permitted Transfer, if the
    proposed Transfer is an assignment or a sublease of more than seventy five percent (75%) of the Premises for a term longer than seventy five percent (75%) of the then remaining Term, then Landlord shall have the right in its sole and absolute
    discretion to terminate this Lease by sending Tenant written notice of such termination within thirty (30) days after Landlord&#8217;s receipt of Tenant&#8217;s notice requesting consent to the Transfer. If Landlord elects to terminate this Lease, Tenant may
    withdraw its notice requesting consent to the Transfer by providing written notice within five (5) business days after Landlord&#8217;s termination (with time being of the essence), in which case Landlord&#8217;s termination shall be negated, and the Lease shall
    continue pursuant to its terms. If Landlord elects to terminate this Lease, then Tenant shall tender the Premises to Landlord in the condition required by this Lease at the end of the Term, and this Lease shall terminate, on the proposed effective date
    of the requested Transfer, and Tenant shall have no further obligations under this Lease except for those accruing prior to the termination date and those that, pursuant to the terms of the Lease, survive the expiration or early termination of the
    Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except for a Permitted Transfer, in the event,
    if any, that (i) all rent and other consideration that Tenant receives as a result of a Transfer exceeds (ii) the Rent payable to Landlord for the portion of the Premises and Term covered by the Transfer (allocated on a per square foot basis), then
    Tenant shall, at Landlord&#8217;s election, pay to Landlord an amount equal to fifty percent (50%) of such excess, from time to time on a monthly basis upon Tenant&#8217;s receipt of such excess; provided that in determining any such excess, Tenant may deduct from
    the excess all reasonable and customary expenses directly incurred by Tenant in connection with such Transfer, except that any construction costs incurred by Tenant in connection with such Transfer shall be deducted on a straight-line basis over the
    term of the applicable Transfer. If Tenant is in Default, Landlord may require that all sublease payments be made directly to Landlord, in which case Tenant shall receive a credit against Rent in the amount of Tenant&#8217;s share of payments received by
    Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">28</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Without limiting Landlord&#8217;s right to withhold
    its consent to any transfer by Tenant, and regardless of whether Landlord shall have consented to any such transfer, neither Tenant nor any other person having an interest in the possession, use or occupancy of the Premises or any part thereof shall
    enter into any lease, sublease, license, concession, assignment or other transfer or agreement for possession, use or occupancy of all or any portion of the Premises that provides for rent or other payment for such use, occupancy or utilization based,
    in whole or in part, on the net income or profits derived by any person or entity from the space so leased, used or occupied, and any such purported lease, sublease, license, concession, assignment or other transfer or agreement shall be absolutely
    void and ineffective as a conveyance of any right or interest in the possession, use or occupancy of all or any part of the Premises..</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">5.5.6 </font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Section 5.5 shall survive the expiration or
    earlier termination of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 6</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">INDEMNIFICATION; RELEASE; INSURANCE</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> 6.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Indemnification and Release</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>To the extent permitted by Applicable Law,
    Tenant shall protect, indemnify, release, defend and hold Landlord (and the Landlord Parties) harmless from and against any and all Claims to the extent caused by or incurred by reason of: (a) any damage to any property (including the property of
    Landlord), or any injury (including death) to any person, occurring in, on, or about any portion of the Premises, except to the extent caused by or arising from the gross negligence or willful misconduct of Landlord or the Landlord Parties; (b) any
    Alterations, work, or other thing done by Tenant or any Tenant Parties in or about any portion of the Premises, or from transactions of Tenant concerning any portion of the Premises; (c) Tenant&#8217;s failure to comply with any Applicable Laws; (d) any
    breach or default by Tenant of any representation, covenant or other term of this Lease; provided that Tenant shall not be obligated to so indemnify Landlord to the extent any such matter arises from, or is caused by, the willful misconduct or gross
    negligence of Landlord or the Landlord Parties; or (e) Tenant&#8217;s use and occupancy of the Premises. Tenant&#8217;s agreement to indemnify, defend and hold the Landlord and the Landlord Parties (the &#8220;<b>Indemnitees</b>&#8221;) harmless is conditioned upon the
    Indemnitees (i) providing written notice to Tenant of any claim, demand or action arising out of the indemnified activities within thirty (30) days after Landlord has actual knowledge of such claim, demand or action, provided that the failure to so
    notify Tenant will not relieve Tenant of its obligations hereunder except to the extent such failure has actually materially prejudiced Tenant; (ii) permitting Tenant to assume full responsibility to investigate, prepare for and defend against any such
    claim or demand, subject to Landlord&#8217;s reasonable approval of any counsel used in the defense of such claim or demand; (iii) assisting Tenant, at Tenant&#8217;s expense, in the reasonable investigation of, preparation of and defense of any such claim or
    demand; and (iv) not settling such claim or demand that would result in a payment in excess of $100,000 (individually or in the aggregate) without Tenants&#8217; prior written consent, which shall not be unreasonably withheld, conditioned, or delayed. &#8220;<b>Claims</b>&#8221;
    mean claims, demands, losses, penalties, fines, liabilities, actions (including informal proceedings), settlements, judgments, damages, reasonable costs, and reasonable expenses (including reasonable attorneys&#8217; fees and consultants&#8217; fees, court costs,
    and other litigation expenses) of whatever kind or nature, known or unknown, contingent or otherwise, incurred or suffered by, or asserted against, the party in question.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">29</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant hereby releases Landlord and the Landlord
    Parties from any and all liability for any loss or claim, including all economic losses and all consequential and indirect losses, as a result of loss, damage or injury to the property and persons of Tenant and its employees, as a result of any
    occurrence in, upon or at the Premises or the occupancy or use by the Tenant of the Premises, including damage to the Building or loss of access to the Premises, whether or not such loss or claim may have arisen out of the acts, omissions or negligence
    of Landlord, the Landlord Parties or those for whom Landlord or the Landlord Parties are in law responsible. Except with respect to Sections 1.3 and 3.3.4, Landlord hereby releases Tenant from any and all liability for consequential or special damages,
    including lost profits (which shall not limit the rights and remedies of Landlord expressly provided in this Lease).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> 6.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Insurance</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Insurance</u>. Landlord shall
    obtain and keep in force throughout the Term the following coverages in the following amounts: (a) commercial general liability insurance on an &#8220;occurrence&#8221; basis on the current ISO CG 00 01 occurrence form or its equivalent with a deductible
    reasonably acceptable to Landlord with a limit of not less than $5,000,000 per occurrence, (b) property damage insurance covering the core and shell of the Building and structural elements of other improvements situated upon the Premises on a
    replacement cost basis against loss or damage as provided by the standard fire and extended coverage policy, including, without limitation, earthquake and terrorism, and all other risks of direct physical loss as insured against under a special
    extended coverage endorsement in amounts and with a deductible determined by Landlord in its commercially reasonable discretion, (c) boiler and machinery insurance on a repair or replace basis, (d) business interruption insurance with respect to
    insurance required under (b) and (c) above with an indemnity period determined by Landlord, and (e) any such other insurance as Landlord&#8217;s lender may require. Tenant shall provide Landlord with such information from time to time as Landlord may
    reasonably require in connection with Landlord&#8217;s determination of the insurance required pursuant to clause (b), above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Insurance.</u> Tenant shall procure
    and maintain during the Lease Term, at its sole cost and expense, a policy or policies of insurance protecting Landlord and Tenant against each of the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Commercial general liability
    insurance with respect to the operations of Tenant insuring against bodily injury or death and property damage in amounts (i) not less than $10,000,000 in the aggregate,(ii) not less than $2,000,000 per occurrence and (iii) not less than $10,000,000 of
    excess umbrella liability insurance. Such insurance shall contain separation of insured clauses and separation of insureds, with Landlord and any third party now or hereafter providing financing to Landlord where such third party has a security
    interest in the Premises under such financing shall be included as additional insureds. Tenant may satisfy the foregoing limits through any combination of primary and umbrella/excess policies, provided the combined total coverage is not less than
    $20,000,000 in the aggregate. The amount of such commercial general liability insurance shall be increased from time to time as Landlord may reasonably determine. All such bodily injury and property damage insurance shall insure Tenant&#8217;s exposure with
    respect to the indemnity agreement as to personal injury or property damage contained in Section 6.1 herein.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">30</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Insurance covering Tenant&#8217;s
    construction, alterations, additions or improvements permitted herein (other than the core and shell of the Building and structural elements of other improvements), existing tenant improvements, trade fixtures and personal property, in an amount not
    less than 100% of their full replacement cost from time to time during the Lease Term, providing protection on an all risk basis, including, without limitation, coverage for earthquakes with coverage commencing on or prior to the commencement of
    Tenant&#8217;s construction, for the repair or replacement of the property damaged or destroyed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Pollution Legal Liability that
    provides first party coverage for clean-up costs and third party coverage for bodily injury and property damage resulting from pre-existing and future contamination conditions, of at least Five Million Dollars ($5,000,000.00) per pollution event; such
    coverage shall specifically include this lease as an insured contract.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The minimum limits of
    insurance required to be carried by Tenant shall not limit Tenant&#8217;s liability. All policies of insurance to be provided by Tenant shall be issued by insurance companies, with general policy holder&#8217;s rating of not less than A and a financial rating of
    not less than Class VIII as rated in the most current available &#8220;Best&#8217;s&#8221; Insurance Reports, and admitted to do business in the State of California. Such policies shall be issued in the name of Tenant, with Landlord, Landlord&#8217;s managing agent, lenders,
    and any other party designated by Landlord (&#8220;<b>Additional Insured Parties</b>&#8221;) included as an additional insured. Tenant&#8217;s property insurance and any builder&#8217;s risk policy carried by Tenant or its contractors shall identify Landlord or, at Landlord&#8217;s
    direction, Landlord&#8217;s lender, as a loss payee. The full replacement cost of improvements under Tenant&#8217;s property insurance may be designated by Landlord in the good faith exercise of Landlord&#8217;s judgment. In the event that Tenant does not agree with
    Landlord&#8217;s designation, Tenant shall have the right to submit the matter to an insurance appraiser reasonably selected by Landlord and paid for by Tenant. The insurance appraiser shall submit a written report of his appraisal, and if said report
    discloses that the improvements are not insured as therein required, Tenant shall promptly obtain the insurance required. The policies provided by Tenant shall be for the mutual and joint benefit and protection of Landlord and Tenant, and certificates
    of insurance shall be delivered to the Landlord within ten (10) days after the Lease Commencement Date and, thereafter, within thirty (30) days after to the expiration of the term of each such policy. Upon Landlord&#8217;s request, Tenant shall deliver to
    Landlord, in lieu of such certificates, copies of the policies of insurance required to be carried under Section 6.2.2 showing that the Additional Insured Parties are named as additional insureds (with respect to the applicable policies). Upon the
    expiration or termination of any such policy, renewal or additional policies shall be procured and maintained by the Tenant to provide the required coverage. All policies of insurance delivered to Landlord must contain a provision that the company
    writing said policy will provide Landlord with thirty (30) days&#8217; notice in writing in advance of any cancellation or lapse or the effective date of any reduction in the amounts of insurance (except in the event of non-payment of premium, in which case
    ten (10) days&#8217; written notice shall be given). Notwithstanding the foregoing, if the foregoing requirement that the insurance company provide prior notice to Landlord of cancellation or material change of the applicable policy cannot reasonably be
    obtained based on then-prevailing insurance industry practices, Tenant shall so advise Landlord of such unavailability and shall instead shall use reasonable efforts to cause its insurer to provide Landlord, and in any event Tenant shall provide
    Landlord with, notice of any such cancellation of any of Tenant&#8217;s insurance policies. All of Tenant&#8217;s commercial general liability, property damage and other casualty policies shall be written as primary policies, not contributing with and not in
    excess of coverage which Landlord may carry. Tenant agrees that if, after the Commencement Date, Tenant does not take out and maintain the insurance required under this Section 6.2, Landlord may (but shall not be required to) procure, and thereafter
    maintain, said insurance on Tenant&#8217;s behalf, and any costs or expenses incurred by Landlord in connection therewith, plus an administration fee of ten percent (10%) of the cost, shall promptly be paid by Tenant to Landlord as Additional Rent.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">31</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Notwithstanding anything to
    the contrary, Tenant&#8217;s obligation to carry the insurance described in this Section 6.2.2 may be brought within the coverage of a so-called blanket policy or policies of insurance carried and maintained by the Tenant, provided that (i) Landlord will be
    an additional insured thereunder as its interests may appear; (ii) the coverage afforded Landlord will not be reduced or diminished by reason of the use of such blanket policy of insurance; and (iii) the requirements set forth herein are otherwise
    satisfied. In the event of any Claims covered by Tenant&#8217;s insurance, Tenant shall, within 10 days following Landlord&#8217;s written request, provide Tenant with copies of the applicable insurance policies carried by Tenant pursuant to this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Release of Subrogation Rights</u>. Tenant and
    Landlord each hereby releases the other from liability and waives all right to recover against the other for any loss from perils insured against under their property insurance policies, including any extended coverage and special form endorsements to
    said policies; provided, however, this <u>Section 6.2.3</u> shall be inapplicable if it would have the effect, but only to the extent that it would have the effect of invalidating any insurance coverage of Landlord or Tenant. Tenant and Landlord&#8217;s
    property damage policies shall contain, if available, a waiver of subrogation clause.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">6.2.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Insurance for Alterations</u>. During the
    performance of any Alterations by Tenant, (a) the insurance required under this <u>Section 6.2</u> shall extend to all of Tenant&#8217;s consultants and contractors (and subcontractors of any tier) and shall include injuries to persons and damage to
    property arising in connection with such Alterations and (b) Tenant shall also maintain such other insurance as Landlord may reasonably require, including all-risk builder&#8217;s insurance, each of which policies shall name Landlord and Landlord&#8217;s lender as
    additional insureds and loss payees. Tenant shall give to Landlord copies of the policies of such insurance prior to commencing construction of such Alterations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: 0.5in">ARTICLE 7</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: 0.5in">THIRD PARTIES</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Subordination, Attornment and
      Non-Disturbance</u>. This Lease shall be automatically subject and subordinate at all times to the lien of any first priority mortgages or deeds of trust on, against, or affecting any portion of the Premises, or Landlord&#8217;s interest or estate in any
    portion of the Premises, and to all renewals, modifications, consolidations, replacements, and extensions thereof (each, a &#8220;<b>Mortgage</b>&#8221;); provided that, as a condition precedent to such subordination, Tenant must receive a fully executed
    subordination, non-disturbance and attornment agreement substantially in the form attached as Exhibit E hereto, or in such other commercially reasonable form as required by Landlord&#8217;s Mortgagee (as hereinafter defined) (a &#8220;<b>SNDA</b>&#8221;) from any
    current and future encumbrance holder (each, a &#8220;<b>Mortgagee</b>&#8221;) with such changes as reasonably requested by Tenant. Landlord shall request a SNDA from each present and any future Mortgagee seeking to subordinate this Lease to the lien of its
    Mortgage and deliver the same to Tenant. In the event Mortgagee enforces it rights under the Mortgage, Tenant, at Mortgagee&#8217;s option, will attorn to Mortgagee or its successor; provided, however, that, subject to the terms of any SNDA between Tenant
    and such Mortgagee (which shall govern in the event of any conflicts with the provisions of this Section 7.1), Mortgagee or its successor shall not be liable for or bound by (i) any payment of any Rent installment that may have been made more than
    thirty (30) days before the due date of such installment, (ii) any act or omission of or default by Landlord under this Lease (but Mortgagee, or such successor, shall be subject to the continuing obligations of landlord under the Lease arising from and
    after such succession, but only to the extent of Mortgagee&#8217;s, or such successor&#8217;s, interest in the Premises as provided in Article 12), (iii) any then- exercisable credits, claims, setoffs or defenses that Tenant may have against Landlord, or (iv) any
    obligation to provide tenant improvements allowances or perform tenant improvements to be provided by Landlord hereunder.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Mortgagee&#8217;s Right to Cure</u>.
    Notwithstanding anything to the contrary in this Lease, before exercising any right (a) of offset, counterclaim, reduction, deduction, or abatement against Tenant&#8217;s payment of Rent under this Lease or (b) to terminate the Lease or to claim a partial or
    total eviction, in each case arising from Landlord&#8217;s default under this Lease, (i) Tenant shall provide to each Mortgagee whose name and address has been furnished in writing to Tenant with written notice of the default by Landlord giving rise to same,
    and (ii) Mortgagee shall have a period of thirty (30) days after the last date on which Landlord could have cured such default within which such Mortgagee will be permitted, but not be obligated, to cure such default. If such default cannot be cured
    within such thirty-(30)-day period, then such Mortgagee shall have such additional time as may be necessary to cure such default, if prior to the end of such thirty-(30)-day period such Mortgagee has commenced and is diligently pursuing such cure or
    the remedies under the Mortgage necessary for Mortgagee to be able to effect such cure, in which event Tenant shall have no right with respect to such default while such cure and remedies are being diligently pursued by such Mortgagee. Notwithstanding
    the foregoing, such Mortgagee shall have no obligation to cure (and shall have no liability or obligation for not curing) any default by Landlord. In addition, as to any default by Landlord the cure of which requires possession and control of the
    Premises, provided that such Mortgagee undertakes by written notice to Tenant to exercise reasonable efforts to cure or cause to be cured by a receiver such default within the period permitted by this <u>Section 7.2</u>, such Mortgagee&#8217;s cure period
    shall continue for such additional time as such Mortgagee may reasonably require to either: (A) obtain possession and control of the Premises with due diligence and thereafter cure the default with reasonable diligence and continuity; or (B) obtain the
    appointment of a receiver and give such receiver a reasonable period of time in which to cure the default.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Sale of the Premises</u>. Subject to the
    provisions of Article 11, if Landlord sells or conveys the Premises, such sale or conveyance shall release Landlord from any liability from and after such sale or conveyance upon any of the covenants or conditions, expressed or implied, contained in
    this Lease in favor of Tenant (to the extent such liability is expressly assumed by such transferee), and in such event, Tenant agrees to look solely to the successor-in-interest of Landlord in and to this Lease with respect to such liabilities that
    are incurred from and after such sale or conveyance. In the event Landlord enters into a purchase and sale agreement for the sale or conveyance of the Premises, in the event such purchaser is an entity engaged primarily in the business of research,
    development, manufacturing, sale, or marketing of a biopharmaceutical product (a &#8220;<b>Pharma Competitor</b>&#8221;), then the Pharma Competitor shall execute a non-disclosure and confidentiality agreement substantially in the form attached hereto as <u>Exhibit






      F</u>; provided, however, that Tenant shall negotiate in good faith in the event the Pharma Competitor wishes to deviate from the form attached as <u>Exhibit F</u>. Except as set forth in this <u>Section 7.3</u>, this Lease shall not be affected by
    any such sale or conveyance and Tenant agrees to attorn to the purchaser or assignee. Landlord shall transfer or deliver the Security Deposit to Landlord&#8217;s successor-in-interest and thereupon Landlord shall be discharged from any further liability with
    regard thereto.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">7.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Estoppel Certificates</u>. Within ten (10)
    business days after Landlord&#8217;s written request, Tenant shall execute and deliver to Landlord and any of Landlord&#8217;s then existing or prospective lenders, investors, or purchasers of any portion of the Premises, a certificate substantially in the form
    attached as <u>Exhibit C</u>, or in such other commercially reasonable form and containing such other information as Landlord or any such lenders, investors, or purchasers, may reasonably require. Any certificate delivered in accordance with this <u>Section






      7.4</u> may be relied upon by any such lender, investor, or purchaser. Within ten (10) business days after Tenant&#8217;s request, Landlord shall execute and deliver to Tenant and any of Tenant&#8217;s then existing or prospective lenders, investors, or
    purchasers, a statement in writing certifying that Tenant is in possession of the Premises under the terms of this Lease, that this Lease is unmodified and in full force and effect (or, if there have been modifications, that this Lease is in full force
    and effect, as modified, and setting forth such modifications), stating the dates to which rent has been paid, and either stating that no defaults exist hereunder, or specifying each such default of which Landlord may have knowledge, and such other
    matters as may be reasonably requested by Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-size: 10pt">7.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Liens</u>.
      Tenant shall, within fifteen (15) business days of written notice of filing, discharge (either by payment or by filing of the necessary bond, insure over, or otherwise) any mechanic&#8217;s, materialman&#8217;s or other lien or encumbrance against any portion of
      the Premises that arises out of any payment due for, or purported to be due for, any labor, services, materials, supplies or equipment alleged to have been furnished to or for Tenant. If Tenant shall fail to so discharge such lien or encumbrance
      (either by payment or by filing of the necessary bond, insure over or otherwise) then, such failure shall be an Event of Default under this Lease and, in addition to any other right or remedy of Landlord, Landlord may discharge the same (either by
      payment or by filing of the necessary bond or otherwise), and any payment, costs and expenses incurred by Landlord in connection therewith, including reasonable attorneys&#8217; fees, shall be repaid together with interest thereon at the rate set forth in
      <u>Section 2.3</u> from the date of payment. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant may contest any lien (and Landlord shall not discharge such lien at Tenant&#8217;s expense for so long as Tenant is diligently
      pursuing such contest) if (i) such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord in writing of such dispute, (iii) Tenant has </font>or establishes unrestricted
    cash reserves to in an amount equal to 125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contested lien and (iv) such lien is fully bonded by Tenant to the reasonable
    satisfaction of Landlord and any Mortgagee.&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"></p>
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE 8&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>EVENTS OF DEFAULT &amp; REMEDIES</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"> 8.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Events of Default</u>. &#8220;<b>Event of Default</b>&#8221; means any of the following:</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant fails to pay when due
    any Rent, and such failure continues for five (5) business days after Landlord delivers to Tenant notice thereof; provided, however, Landlord shall not be required to provide prior notice of Tenant&#8217;s failure to pay any recurring obligation to pay any
    Base Rent or any monthly payment of estimated Taxes or Insurance Expenses more than twice during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be an Event of Default if Tenant fails to pay the amount when due and
    such failure continues for five (5) business days after the due date;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>except as otherwise provided
    in this Lease, Tenant fails to comply with any term, provision, or covenant of this Lease and such failure continues for thirty (30) days after Landlord gives to Tenant Notice thereof (but if such failure is curable but cannot reasonably be cured
    during such 30-day period, and if Tenant has commenced such cure promptly and in any case within such 30-day period and thereafter has diligently pursued such cure to completion, then such 30-day period shall be extended to ninety (90) days);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant fails to obtain and
    keep in force at all times any insurance required under this Lease, and such failure continues for five (5) days after Landlord gives to Tenant Notice thereof;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant fails to deliver to
    Landlord, within fifteen (15) business days after Landlord gives Tenant Notice thereof, any instrument or assurance required under this Lease;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>The filing by Tenant in any
    court pursuant to any statute or petition in bankruptcy or insolvency or for reorganization or arrangement for the appointment of a receiver or all of a portion of Tenant&#8217;s property the filing against Tenant of any such petition, or the commencement of
    a proceeding for the appointment of a trustee, receiver or liquidator for Tenant, or of any property of Tenant, or a proceeding by any governmental authority for the dissolution or liquidation of Tenant, if such proceeding shall not be dismissed or
    trusteeship discontinued within sixty (60) days of commencement of such proceeding or the appointment of such trustee or receiver; or the making by Tenant of an assignment for the benefit of creditors. Tenant hereby stipulates to the lifting of the
    automatic stay in effect and relief from such stay for Landlord in the event Tenant files a petition under the United States Bankruptcy Laws, for the purpose of landlord pursuing its rights and remedies against Tenant;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant&#8217;s failure to cause to
    be released any mechanics liens filed against the Premises within twenty (20) days after the date Tenant is notified that the same shall have been filed or recorded, subject to Tenant&#8217;s right to dispute liens as set forth in <u>Section 7.5</u>;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Abandonment of the Premises
    pursuant to California Civil Code Section 1951.3, or failure by Tenant or a transferee permitted pursuant to Article 5 to occupy at least sixty percent (60%) of the Premises for a period of ninety (90) consecutive days or more for any reason other than
    restoration following a casualty or condemnation, Force Majeure affecting Tenant&#8217;s ability to operate within the Premises, and temporary cessations in order to complete Alterations in accordance with this Lease, provided that it shall not be deemed to
    be a failure to occupy for purposes of this clause (ii) if the applicable portion of the Premises remains fully furnished with the necessary equipment to conduct business operations consistent with the Permitted Use as it was undertaken prior to such
    failure to occupy, with regular repair, maintenance, and cleaning occurring in accordance with the terms of this Lease, no other Event of Default has occurred, and Tenant is actively marketing the applicable portion of the Premises for sublease (or
    marketing this Lease for assignment);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Tenant&#8217;s failure to provide a
    SNDA within the period required by Section 7.1 or Tenant&#8217;s failure to provide a certificate within the time period required by Section 7.4 and such failure continues for five (5) business days after Landlord delivers to Tenant notice thereof;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(i) </font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant performs a Transfer
    in violation of Article 5, or</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(j)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>If Landlord elects, in its
    sole discretion, the occurrence of any &#8220;Event of Default&#8221; under the Companion Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">8.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Remedies</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif">8.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Upon Event of Default</u>.
    Upon the occurrence of any Event of Default, Landlord shall have the option to pursue any one or more of the following remedies without any Notice or demand whatsoever (except as expressly provided herein), concurrently or consecutively and not
    alternatively (in addition to any other remedies available to Landlord at law or in equity), all of which remedies shall be distinct, separate and cumulative:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in"><font style="font-family: Times New Roman, Times, Serif">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Termination</u>. Landlord
    may terminate this Lease upon notice to Tenant, in which event Tenant shall vacate the Premises immediately and deliver possession of the Premises to Landlord in the condition which Tenant is required to surrender the Premises at the expiration of the
    Term (Tenant hereby waives, relinquishes and releases for itself and for all those claiming under Tenant any right of occupancy of the Premises following termination of this Lease, and any right to redeem or reinstate this Lease by order or judgment of
    any court or by any legal process or writ under Applicable Laws, including, without limitation, California Code of Civil Procedure Sections 473 and 1179, and California Civil Code Section 3275), and if Tenant fails to do so, then Landlord may, after
    due process of law, enter upon and take possession of the Premises, and expel or remove Tenant and any other person who may be occupying the Premises or any portion thereof, without being liable for prosecution or any claim or damages therefor. Upon
    termination of the Lease as provided in this Section, Landlord may recover from Tenant the following: (i) the worth at the time of award of any unpaid rent which has been earned at the time of such termination; plus (ii) the worth at the time of award
    of the amount by which the unpaid rent which would have been earned after termination until the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iii) the worth at the time of award of the
    amount by which the unpaid rent for the balance of the Term after the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iv) any other amount necessary to compensate Landlord for all the
    detriment proximately caused by Tenant&#8217;s failure to perform its obligations under this Lease or which in the ordinary course of things would be likely to result therefrom, specifically including but not limited to, attorneys&#8217; fees, brokerage
    commissions and advertising expenses incurred, expenses of remodeling the Premises or any portion thereof for a new tenant, whether for the same or a different use, and any special concessions made to obtain a new tenant; plus (v) at Landlord&#8217;s
    election, such other amounts in addition to or in lieu of the foregoing as may be permitted from time to time by Applicable Law. The term &#8220;rent&#8221; as used in this Section 8.2.1(a) shall be deemed to be and to mean all sums of every nature required to be
    paid by Tenant pursuant to the terms of this Lease, whether to Landlord or to others, including, without limitation, late charges and interest. As used in Sections 8.2.1(a)(i) and (ii), the &#8220;worth at the time of award&#8221; shall be computed by allowing
    interest at the rate set forth in Section 2.4 above, but in no case greater than the maximum amount of such interest permitted by Applicable Law. As used in Section 8.2.1(a)(iii), the &#8220;worth at the time of award&#8221; shall be computed by discounting such
    amount at the discount rate of the Federal Reserve Bank of San Francisco at the time of award plus one percent (1%). Landlord shall have no obligation to relet the Premises or any part thereof and shall in no event be liable for failure to relet the
    Premises or any part thereof, or, in the event of any such reletting, for refusal or failure to collect any rent due upon such reletting. No such refusal or failure shall operate to relieve Tenant of any liability under this Lease. Tenant shall instead
    remain liable for all unpaid Rent and for all such expenses. This paragraph is expressly intended to afford Landlord the remedies provided for in California Civil Code &#167; 1951.2.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Possession</u>. Landlord
    may re-enter the Premises without terminating this Lease by Notice to Tenant and sublet the whole or any part thereof for the account of Tenant upon as favorable terms and conditions as the market will allow; <u>provided</u>, <u>however</u>, that
    Tenant shall have not less than thirty (30) days following such re-entry to remove Tenant&#8217;s Personalty from the Premises. In the latter event (a) Landlord shall have the right to collect any Rent which may thereafter become due and payable under such
    sublease and to apply the same first, to the payment of any expenses incurred by Landlord in dispossessing Tenant and in subletting the Premises, and second, to the payment of the Rent herein reserved and to the fulfillment of Tenant&#8217;s other covenants
    hereunder, and (b) Tenant shall be liable for amounts equal to the Rent as the same would under the terms of this Lease become due, less any amounts actually received by Landlord and applied on account of Rent as aforesaid. Landlord shall have the
    remedy described in California Civil Code Section 1951.4 (lessor may continue lease in effect after lessee&#8217;s breach and abandonment and recover rent as it becomes due, if lessee has the right to sublet or assign, subject only to reasonable
    limitations). Accordingly, if Landlord does not elect to terminate this Lease due to any Event of Default, Landlord may, from time to time, without terminating this Lease, enforce all of its rights and remedies under this Lease, including, without
    limitation, the right to recover all Rent as it becomes due.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Subleases of Tenant</u>.
    Whether or not Landlord elects to terminate this Lease, Landlord may terminate any and all subleases or other consensual arrangements for possession or occupancy of the Premises entered into by Tenant or any subtenant of Tenant, or may succeed to
    Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in such subleases or other arrangements. If Landlord elects to succeed to Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in any such subleases or other arrangements, then as of the date of Notice by Landlord of such
    election (i) Tenant shall have no further right to, or interest in, the rent or other consideration receivable thereunder, and (ii) any sublessee or other occupant of the Premises shall attorn to and recognize Landlord as its landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(e)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Right to Perform Tenant&#8217;s
      Covenants</u>. If Tenant shall at any time fail to pay any Taxes or to take out, pay for, maintain or deliver any of the insurance provided for in this Lease, or shall fail to make any other payment or perform any obligation under this Lease, and
    such failure continues beyond applicable notice and cure periods (or without any notice and right to cure where required to protect life or property), then Landlord may, without waiving or releasing Tenant from any obligations of Tenant in this Lease
    contained, pay any such Tax, effect any such insurance coverage and pay premiums therefor, and make any other payment or perform any other act which Tenant is obligated to perform under this Lease, in such manner and to such extent as Landlord shall,
    in its sole discretion, deem necessary. In exercising any such rights, Landlord may pay necessary and incidental costs and expenses including reasonable attorneys&#8217; fees. All sums so paid by Landlord and all necessary and incidental costs and expenses
    in connection with the performance of any such act by Landlord, together with interest thereon at the Interest Rate, shall be payable to Landlord on demand. If Landlord incurs any third-party expenses to cure a breach of any non-monetary obligation of
    Tenant, Tenant shall also pay an administrative charge equal to ten percent (10%) of the cost of the work performed by Landlord. Landlord shall have no obligation to perform on Tenant&#8217;s behalf and if Landlord does so, Landlord shall not be liable to
    Tenant for any damage resulting from its actions.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0.5in">(f)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Other Remedies</u>. In
    addition to the remedies set forth in this Lease, Landlord shall have all other remedies provided by law or statute to the same extent as if fully set forth herein word for word (including, without limitation, the right to enforce Tenant&#8217;s specific
    performance of each and every covenant, condition and other provisions of this Lease). No remedy herein conferred upon, or reserved to Landlord shall exclude any other remedy herein or by law provided, but each shall be cumulative.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">8.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Form of Payment Following Event of Default</u>.
    Following the occurrence of a monetary Event of Default, Landlord shall have the right to require that any or all subsequent amounts paid by Tenant to Landlord under this Lease, whether relating to the Event of Default in question or otherwise, be paid
    in the form of wire transfer or immediately available funds, or by other means approved by Landlord, notwithstanding any prior acceptance by Landlord of payments from Tenant in any different form.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">38</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">8.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Mitigation of Damages</u>. Except as required
    by law, Landlord shall have no obligation to mitigate its damages. If Landlord is required by law to mitigate its damages under this Lease, then (a) Landlord shall be required only to use reasonable efforts to so mitigate, which shall not exceed such
    efforts as commercial landlords generally use to lease similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California; (b) Landlord shall not be deemed to have failed to so mitigate if Landlord leases
    less than all of the Premises; and (c) Landlord&#8217;s failure to so mitigate shall only reduce the Rent to which Landlord is entitled. Tenant acknowledges that Landlord&#8217;s rejection of a prospective replacement tenant based on an offer of rentals below
    published rates for new leases of similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California at the time in question, or containing terms less favorable than those contained herein, shall not give
    rise to a claim by Tenant that Landlord failed to so mitigate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">8.2.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Waiver of Right of Redemption</u>. Tenant
    (for itself and all others claiming through Tenant) irrevocably waives and releases any rights under any law now or hereafter existing to redeem or reinstate this Lease or Tenant&#8217;s right of occupancy of the Premises after termination of this Lease,
    including, without limitation, any and all rights conferred by Section 3275 of the Civil Code of California and by Sections 1174(c) and 1179 of the Code of Civil Procedure of California..</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">8.2.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Reimbursement of Expenses</u>. In the case of
    termination of this Lease pursuant to this Section 8.2, Tenant shall reimburse Landlord for all expenses arising out of such termination, including without limitation, all costs incurred in collecting amounts due from Tenant under this Lease (including
    legal fees, costs of litigation and the like); all expenses incurred by Landlord in attempting to relet the Premises or parts thereof (including advertisements, brokerage commissions, Tenant&#8217;s allowances, costs of preparing space, and the like); all of
    Landlord&#8217;s then unamortized costs of any work allowances provided to Tenant for the Premises; and all Landlord&#8217;s other reasonable expenditures necessitated by the termination. The reimbursement from Tenant shall be due and payable immediately from time
    to time upon notice from Landlord that an expense has been incurred, without regard to whether the expense was incurred before or after the termination.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">8.2.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Claims in Bankruptcy</u>. Nothing herein
    shall limit or prejudice the right of Landlord to prove and obtain in a proceeding for bankruptcy, insolvency, arrangement or reorganization, by reason of the termination, an amount equal to the maximum allowed by a statute or Applicable Law in effect
    at the time when, and governing the proceedings in which, the damages are to be proved, whether or not the amount is greater to, equal to, or less than the amount of the loss or damage that Landlord has suffered.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">8.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Landlord Default</u>. If Landlord shall fail
    to perform any material obligation under this Lease required to be performed by Landlord, Landlord shall not be deemed to be in default hereunder nor subject to claims for damages of any kind, unless such failure shall have continued for a period of
    thirty (30) days after written notice thereof by Tenant or, if such failure is curable but cannot reasonably be cured during such 30-day period, such additional time as it would reasonably take to cure. If Landlord shall fail to cure within the time
    permitted for cure herein, Landlord shall be liable to Tenant for those actual damages sustained by Tenant as a result of Landlord&#8217;s default and Tenant shall also have the right to pursue injunctive relief against Landlord, to the extent available
    under Applicable Laws. Except as may be expressly provided in this Lease, in no event shall Tenant have the right to terminate the Lease nor shall Tenant&#8217;s obligation to pay Base Rent or other charges under this Lease abate based upon any default by
    Landlord of its obligations under the Lease. In no event shall Landlord or any Landlord Related Party ever be liable to Tenant for loss of profits, loss of business, or indirect or consequential damages suffered by Tenant from whatever cause.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">39</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">8.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Non-Waiver</u>. The failure of Landlord to
    insist upon strict performance of any of the terms, covenants, conditions or agreements contained herein shall not be deemed a waiver of any rights or remedies that Landlord may have, and shall not be deemed a waiver of any subsequent breach or default
    in the performance of any of the terms, covenants, conditions or agreements contained herein. The performance of each and every term, covenant, condition and agreement to be performed by Landlord pursuant to this Lease shall not be a condition
    precedent to Landlord&#8217;s right to collect Rent or to enforce this Lease. Further, pursuant to the requirements of California Code of Civil Procedure Section 1161.1(c), Tenant is hereby placed on actual notice that Landlord&#8217;s acceptance of Rent shall not
    constitute a waiver by Landlord of (a) any preceding breach by Tenant of any provision of this Lease, other than the failure of Tenant to pay the particular Rent so accepted; or (b) any of Landlord&#8217;s rights, including, without limitation, any rights
    Landlord may have to recover possession of the Premises or to sue for any remaining Rent owed by Tenant.</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 9 <br>
    CASUALTY &amp; CONDEMNATION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Casualty</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Generally</u>. Subject to <u>Section 9.1.2</u>
    below, if the Premises are damaged by fire, the elements or other casualty (collectively a &#8220;<b>Casualty</b>&#8221;), Tenant shall promptly notify Landlord of the same. Except as expressly set forth below, this Lease shall not terminate in the event of damage
    to the Premises by other casualty, nor any other obligation of Tenant hereunder be abated or affected in any way. If all or any portion of the Premises becomes untenantable or inaccessible by a Casualty, Landlord shall cause a general contractor
    selected by Landlord to provide Landlord and Tenant with a written estimate of the amount of time required, using standard working methods, to substantially complete the repair and restoration of the affected portion of the Premises (&#8220;<b>Completion
      Estimate</b>&#8221;). Landlord shall promptly forward a copy of the Completion Estimate to Tenant. Notwithstanding anything to the contrary contained in this Lease, Landlord and Tenant hereby waive the provisions of any Law relating to the matters
    addressed in this Section, and agree that their respective rights for damage to or destruction of the Premises shall be those specifically provided in this Lease, which shall constitute an express agreement between the parties with respect thereto, and
    Landlord and Tenant hereby agree that any Applicable Law, including Sections 1932(2) and 1933(4) of the California Civil Code, with respect to any rights or obligations concerning damage or destruction of leased or hired property, shall have no
    application to this Lease or to any damage or destruction to all or any part of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>. Notwithstanding <u>Section
      9.1.1</u>, if the Completion Estimate indicates that the Premises cannot be made tenantable within twenty-four (24) months from the date the repair is started, then either party shall have the right to terminate this Lease upon written notice to the
    other within ten (10) days after Tenant&#8217;s receipt of the Completion Estimate, which notice, if sent by Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. Tenant, however, shall not have the
    right to terminate this Lease if the Casualty was caused by the negligence or intentional misconduct of Tenant or any Tenant Parties. If (i) the Completion Estimate indicates that the Premises can be made tenantable within thirty-six (36) months from
    the date the repair is started, and (ii) Tenant terminates this Lease pursuant to the first sentence of this <u>Section 9.1.2</u>., then, within thirty (30) days after receipt of Tenant&#8217;s termination notice, Landlord may, in its sole and absolute
    discretion, negate Tenant&#8217;s termination by providing notice to Tenant that Landlord agrees to an abatement of Base Rent beginning immediately following the twenty-fourth (24<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>)
    month after the date the repair is started and ending on the date when Landlord has substantially completed the repair and restoration of the affected portion of the Premises. In addition, if the Premises are damaged by fire, the elements or other
    casualty during the last twelve (12) months of the Term, and the Completion Estimate shows that the restoration cannot be completed within one hundred twenty (120) days after the Casualty, then either party shall have the right, in lieu of Tenant
    fulfilling its obligations under <u>Section 9.1.1</u> above, to terminate this Lease as of the date of the Casualty by notice to the other party within ten (10) business days after the delivery of the Completion Estimate, which notice, if sent by
    Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. If Tenant elects to terminate the Lease pursuant to this <u>Section 9.1.2</u>, Tenant shall (1) assign to Landlord all of Tenant&#8217;s right,
    title and interest in and to any property insurance proceeds received in connection with such casualty for the Tenant Improvements (defined below) and (2) pay to Landlord an amount equal to Tenant&#8217;s deductible under any insurance and/or any applicable
    self-insured retention amount covering the Tenant Improvements. In addition, Landlord, by notice to Tenant within ninety (90) days after the date of the Casualty, shall have the right to terminate this Lease if (1) any Mortgagee requires that the
    insurance proceeds be applied to the payment of the mortgage debt; or (2) a material uninsured loss to the Building or Premises occurs, and, in either case, Tenant does not provide Landlord with sufficient funds (or evidence of the same satisfactory to
    Landlord) to complete such restoration within thirty (30) days after Landlord&#8217;s termination notice.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Restoration</u>. If this Lease is not
    terminated, Landlord shall promptly and diligently, subject to reasonable delays for insurance adjustment or other matters beyond Landlord&#8217;s reasonable control, restore the core and shell of the Building and structural elements of other improvements
    situated upon the Premises, subject to the following provisions. Such restoration shall be to substantially the same condition that existed prior to the Casualty, except for modifications required by Applicable Law or any other modifications deemed
    desirable by Landlord (&#8220;<b>Landlord&#8217;s Restoration</b>&#8221;). Landlord shall be paid a construction management fee equal to three percent (3%) of the hard and soft costs of construction in connection with Landlord&#8217;s Restoration. In no event shall Landlord
    be required to spend more for the Landlord&#8217;s Restoration than the proceeds received by Landlord, whether from Landlord&#8217;s insurance proceeds or proceeds from Tenant. Landlord shall not be liable for any inconvenience to Tenant, or injury to Tenant&#8217;s
    business resulting in any way from the Casualty or the repair thereof. Landlord shall not be responsible for restoration of any portion of the non-structural tenant improvements, any improvements or fixtures installed for Tenant&#8217;s specific business
    operations, or any Alterations (collectively, the &#8220;<b>Tenant Improvements</b>&#8221;). If this Lease is not terminated, upon the substantial completion of Landlord&#8217;s Restoration, Tenant shall diligently and promptly repair all such damage and restore the
    Tenant&#8217;s Improvements (the &#8220;<b>Tenant&#8217;s Restoration</b>&#8221;) to substantially the same quality, use and usability to the Building and related improvements that existed immediately prior to the Casualty.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.1.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>No abatement of Rent</u>. If the Premises are
    damaged or destroyed by casualty, then the Rent shall not be abated and Tenant shall not be entitled to any compensation or damages from Landlord for loss of the use of the Premises, damage to Tenant&#8217;s Personalty or to any Alterations, or any
    inconvenience occasioned by any damage, repair, or restoration.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.1.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Insurance Proceeds</u>. Tenant shall be
    entitled to any and all of the insurance proceeds payable for the damage to the Tenant Improvements, <u>provided</u>, <u>however</u>, that if Tenant elects to terminate this Lease pursuant to <u>Section 9.1.2</u>, then Tenant shall assign and pay
    over to Landlord all insurance proceeds received by or payable to Tenant with respect to damage to the core and shell of the Building and structural elements of other improvements situated upon the Premises (but not Tenant Improvements and Tenant&#8217;s
    Personalty). Whether or not Tenant so elects to terminate this Lease, Tenant shall be entitled to any and all of the insurance proceeds payable for the damage to Tenant&#8217;s Personalty.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Waiver</u>. Tenant (for itself and all
    others claiming through Tenant) irrevocably waives and releases its rights to make repairs at Landlord&#8217;s expense. The provisions of this Lease, including this <u>Section 9.2</u>, constitute an express agreement between Landlord and Tenant with respect
    to any damage to, or destruction of, any portion of the Premises. Any law in respect of any rights or obligations concerning any such damage or destruction in the absence of an express agreement between the parties, and any other law relating to damage
    or destruction of leased premises, whether in effect on the date of this Lease or thereafter, shall have no application to this Lease or any damage or destruction of any part of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Total Condemnation</u>. If after the
    execution of this Lease and prior to the expiration of the Term, all or a significant portion of the Premises shall be permanently taken under power of eminent domain by any public or private authority, or conveyed by Landlord to said authority in lieu
    of such taking (collectively, a &#8220;<b>Taking</b>&#8221;), and if as a result of such Taking: (a) access to the Premises to and from the publicly dedicated roads adjacent to the Premises as of the Effective Date is permanently and materially impaired such that
    Tenant no longer has access to such dedicated road; (b) there is insufficient parking to operate the Premises under Applicable Laws and replacement parking cannot be constructed or provided elsewhere on the Premises; or (c) the taking includes a
    portion of the Building such that the remaining portions are unsuitable for the Permitted Use and the remaining portions of the Premises cannot, in the reasonable opinion of a contractor mutually agreed upon by Landlord and Tenant, be restored to
    useful condition within eighteen (18) months after the Taking (such event, a &#8220;<b>Total Condemnation</b>&#8221;), then, in such event:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Termination</u>. On the date of the Total
    Condemnation, this Lease shall automatically terminate; <u>provided</u>, <u>however</u>, that Tenant&#8217;s obligations under any indemnification provisions of this Lease and Tenant&#8217;s obligation to pay Rent and all other monetary obligations (whether
    payable to Landlord or a third party) accruing under this Lease prior to the date of termination shall survive such termination. If the date of such Total Condemnation is other than the first day of a month, the Base Rent for the month in which such
    Total Condemnation occurs shall be apportioned based on the date of the Total Condemnation</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">42</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">9.3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Award</u>. Landlord shall be entitled to
    receive the entire award payable in connection with a Total Condemnation without deduction for any estate vested in Tenant by this Lease, and Tenant hereby expressly assigns to Landlord all of its right, title and interest in and to every such award
    and agrees that Tenant shall not be entitled to any such award or other payment for the value of Tenant&#8217;s leasehold interest in this Lease; <u>provided</u>, <u>however</u>, that Tenant shall have the right to file any separate claim available to
    Tenant for any taking of Tenant&#8217;s Personalty, loss of goodwill, and for moving and relocation expenses (but only if such payment to Tenant does not reduce any award available to Landlord).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">9.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Partial Condemnation</u>. In the event of a
    Taking which is not a Total Condemnation, neither party shall have the right to terminate this Lease and Landlord shall, using proceeds therefor from the condemning authority, restore the core and shell of the Building and structural elements of other
    improvements situated upon the Premises reasonably sufficient to make a functional unit of the remaining portion of the Premises, and Tenant shall proceed with restoration of the Tenant Improvements to the extent possible to make a functional unit of
    the remaining portion of the Premises. In the event any partial taking materially affects Tenant&#8217;s operations in the Building for the Permitted Use, such that the Premises no longer provides sufficient space for Tenant to carry out its business without
    material interference with the Permitted Use, then, commencing on the date on which Tenant&#8217;s operations are materially affected, the Base Rent shall be abated in proportion to the square footage of the portion of the Building taken.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: 0">ARTICLE 10 <br>
    MISCELLANEOUS</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Notices</u>. Any notice, consent, demand, or
    other communication or document required or permitted to be given under this Lease or pursuant to any law (&#8220;<b>Notice(s)</b>&#8221;), shall be (a) in writing (except as otherwise provided in this Lease), (b) addressed to the intended recipient at its address
    set forth in the Basic Lease Information (provided that each of Landlord and Tenant may change its addresses for the giving of notices by giving written notice thereof to the other party), (c) sent by fully prepaid registered or certified United States
    Mail return receipt requested, or by any nationally recognized overnight courier service furnishing a written record of attempted or actual delivery, and (d) deemed to have been delivered upon actually delivery or rejection of delivery. Any Notice may
    be given by an attorney on behalf of Landlord or Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Certain Representations</u></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.2.1&#160;&#160; </font>Neither of Tenant nor any wholly-owned subsidiary of
    Tenant is (i) in violation of any OFAC Law or Regulation, the U.S. Patriot Act or Anti-Corruption Legislation, (ii) is named by any Executive Order (including the September 23, 2001, Executive Order Blocking Property and Prohibiting Transactions With
    Persons Who Commit, Threaten to Commit, or Support Terrorism) or the United States Treasury Department as a terrorist, &#8220;Specially Designated National and Blocked Person,&#8221; or (iii) (to the Tenant&#8217;s knowledge) acting, directly or indirectly, on behalf of
    any such person. To Tenant&#8217;s actual knowledge, no such person, group, entity or nation owns 20% or more Tenant&#8217;s voting securities. To the Tenant&#8217;s knowledge, the monies used in connection with this Agreement and amounts committed with respect thereto,
    were not and are not derived from any activities that contravene any applicable OFAC Laws and Regulations, the U.S. Patriot Act, AML Legislation or Anti-Corruption Legislation, each as defined below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">43</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.2.2&#160;&#160; </font>As used herein, the term &#8220;<b>AML Legislation</b>&#8221;
    means United States anti-money laundering-related and anti-terrorism financing laws, regulations, and codes of practice applicable to the Tenant, its affiliates, and their operations from time to time, including, any regulations, guidelines or orders
    thereunder. As used herein, the term &#8220;<b>Anti-Corruption Legislation</b>&#8221; means U.S. Foreign Corrupt Practices Act and similar anticorruption and anti-bribery laws of the United States. As used herein, the term &#8220;<b>OFAC Laws and Regulations</b>&#8221; means
    (i) any lists, laws, rules, sanctions and regulations maintained by OFAC pursuant to any authorizing statute, Executive Order or regulation, including the Trading with the Enemy Act, 50 U.S.C. App. &#167; 1 et seq., the International Emergency Economic
    Powers Act, 50 U.S.C. &#167; 1701 et seq., the Iraq Sanctions Act, Pub. L. 101-513, Title V, &#167;&#167; 586 to 586J, 104 Stat. 2047, the National Emergencies Act, 50 U.S.C. &#167;&#167; 1601 et seq., the Antiterrorism and Effective Death Penalty Act of 1996, Pub. L. 104-
    132, 110 Stat. 1214-1319, the United Nations Participation Act, 22 U.S.C. &#167; 287c, the International Security and Development Cooperation Act, 22 U.S.C. &#167; 2349aa-9, the Nuclear Proliferation Prevention Act of 1994, Pub. L. 103-236, 108 Stat. 507, the
    Foreign Narcotics Kingpin Designation Act, 21 U.S.C. &#167;&#167; 1901 et seq., the Iran and Libya Sanctions Act of 1996, Pub. L. 104-172, 110 Stat. 1541, the Cuban Democracy Act, 22 U.S.C. &#167;&#167; 6001 et seq., the Cuban Liberty and Democratic Solidarity Act, 22
    U.S.C. &#167;&#167; 6021-91, and the Foreign Operations, Export Financing and Related Programs Appropriations Act, 1997, Pub. L. 104-208, 110 Stat. 3009-172; (ii) all regulations, executive orders, or administrative orders of any kind issued under these
    statutes, including 31 C.F.R., Subtitle B, Chapter V; and (iii) any other applicable United States civil or criminal federal or state laws, regulations, or orders that (1) limit the use of and/or seek the forfeiture of proceeds from illegal
    transactions; (2) limit commercial transactions with designated countries or individuals believed to be terrorists, narcotics dealers or otherwise engaged in activities contrary to the interests of the United States; or (3) are designed to disrupt the
    flow of funds to terrorist organizations, as all of the foregoing laws may be amended from time to time.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Brokers</u>. Each of Landlord and Tenant
    represents and warrants to the other that such party has not dealt with any broker or finder in connection with this Lease. Each party shall indemnify the other and hold it harmless from any cost, expense, or liability (including costs of suit and
    reasonable attorneys&#8217; fees) for any compensation, commission or fees claimed by any other real estate broker or agent in connection with this Lease or its negotiation by reason of any act or statement of the indemnifying party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>No Waivers</u>. No provision of this Lease
    shall be deemed waived by either party unless expressly waived in a writing signed by the waiving party (and then only to the extent so expressly waived). No waiver shall be implied by delay or any other act or omission of either party. No waiver by
    either party of any provision of this Lease shall be deemed a waiver of such provision with respect to any subsequent matter relating to such provision, and Landlord&#8217;s consent or approval respecting any action by Tenant shall not constitute a waiver of
    the requirement for obtaining Landlord&#8217;s consent or approval respecting any subsequent action. No act or thing done by Landlord or its agents during the Term shall be deemed a termination of this Lease, an acceleration of the Termination Date, or an
    acceptance of the surrender of the Premises, and no agreement to terminate this Lease, accelerate the Termination Date, or accept a surrender of the Premises shall be valid, unless expressly provided in a writing signed by Landlord. Acceptance of the
    full or any partial payment of Rent shall not be deemed Landlord&#8217;s waiver of any breach by Tenant of any provision of this Lease and Landlord&#8217;s acceptance of a lesser amount than the Rent due under this Lease shall not be deemed Landlord&#8217;s waiver of
    Landlord&#8217;s right to receive the full amount of Rent due, nor shall any endorsement or statement on any check or payment or any letter accompanying such check or payment be deemed an accord and satisfaction, and Landlord may accept such partial payment
    without prejudice to Landlord&#8217;s right to recover the full amount of Rent due. Tenant acknowledges that this <u>Section 10.4</u> imparts actual notice to Tenant that Landlord&#8217;s acceptance of partial payment of Rent does not constitute a waiver of any
    of Landlord&#8217;s rights, including any right Landlord may have to recover possession of the Premises. Forbearance by Landlord in enforcing one or more of the remedies provided in this Lease upon an Event of Default shall not be deemed a waiver of such
    Event of Default or of Landlord&#8217;s right to enforce any such remedies with respect to such Event of Default or any subsequent Event of Default. Landlord&#8217;s acceptance of any Rent or of the performance of any other provision of this Lease from any person
    other than Tenant, including any Transferee, shall not be deemed a waiver of Landlord&#8217;s right to approve any Transfer in accordance with <u>Article 5</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">44</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Future Development</u>. Provided the Tenant
    is Ionis Pharmaceuticals, Inc., or an affiliate, and Tenant is operating for the Permitted Use, in no event shall Landlord take any action or permit any actions to be taken that may or will increase or decrease, modify, change or alter the zoning or
    entitlements of the Premises, alter the Building, change the site amenities, or add additional improvements without the express written consent of Tenant. Notwithstanding the foregoing, subject to the terms of this Section 10.5, Landlord reserves all
    rights as may be necessary or desirable to construct additional improvements serving the Premises, the Companion Premises, or both, in connection with the construction of the improvements under the Companion Lease, including, without limitation,
    pedestrian walkways, installation of utilities and utility connections, structured parking, a pedestrian bridge, and site improvements at the Premises, and to modify the Building in connection with any such additional development, all as required by
    the Companion Lease and consistent with the plans and specifications for the construction of the Companion Premises (&#8220;<b>Future Development</b>&#8221;). In connection with any such Future Development, facilities at the Premises may be eliminated, altered, or
    relocated and may also be utilized to serve the Companion Premises. The rights set forth above shall include rights to use portions of the Premises for the purpose of temporary construction staging and related activities and to implement valet parking
    for reserved and unreserved parking spaces for the purpose of facilitating construction during such activities.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.5.1&#160;&#160;&#160;&#160;&#160; </font>Landlord and its representatives, contractors,
    agents, employees and licensees shall have the right during any construction period to enter the Premises to undertake such work; to shore up the foundations, walls, and other improvements at the Premises; to erect scaffolding and protective barricades
    around the Premises; and to do any other act necessary for the safety of the improvements at the Premises or the expeditious completion of such construction. Landlord shall use reasonable efforts not to interfere with the conduct of Tenant&#8217;s business
    and to minimize the extent and duration of any inconvenience, annoyance or disturbance to Tenant resulting from any work pursuant to this Section in or about the Premises, consistent with accepted construction practice, and so long as Landlord uses
    such reasonable efforts Landlord shall not be liable to Tenant for any compensation or reduction of Rent by reason of inconvenience or annoyance or for loss of business resulting from any act by Landlord pursuant to this Section.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">45</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.5.2&#160;&#160;&#160;&#160;&#160; </font>Tenant agrees to enter into any instruments
    reasonably requested by Landlord in connection with the Future Improvements, and for the continued maintenance of such Future Improvements, so long as the same do not materially decrease the rights or materially and adversely increase the obligations
    of Tenant under this Lease, including reciprocal easement agreements, declarations of covenants, and other agreements to facilitate use of the improvements between the Premises and Companion Premises. Tenant agrees not to take any action to oppose any
    application by Landlord for any permits, consents or approvals from any governmental authorities for any redevelopment or additional development of all or any part of the Companion Premises, and will use all commercially reasonable efforts to prevent
    any of Tenant&#8217;s subtenants or assigns, and Tenant&#8217;s and their respective officers, directors, employees, agents, contractors and consultants from doing so. For purposes hereof, action to oppose any such application shall include, without limitation,
    communications with any governmental authorities requesting that any such application be limited or altered. Also for purposes hereof, commercially reasonable efforts shall include, without limitation, commercially reasonable efforts, upon receiving
    notice of any such action to oppose any application on the part of any Tenant Parties, to obtain injunctive relief, and, in the case of a subtenant, exercising remedies against the subtenant under its sublease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 0.5in; text-align: justify">10.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Other Provisions</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.1&#160;&#160; &#160;&#160;&#160;</font><u>Covenant of Quiet Enjoyment</u>. Landlord
    covenants that Tenant, while no Event of Default has occurred and be continuing, shall peaceably and quietly have, hold, and enjoy the Premises for the Term without hindrance from Landlord, but not otherwise, subject to all matters of record and to the
    terms and provisions of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.2&#160;&#160; </font>&#160;&#160;&#160;<u>Survival</u>. All obligations of Tenant under
    this Lease not fully performed as of the Termination Date shall survive the Termination Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.3&#160;&#160; </font>&#160;&#160;&#160;<u>Entire Agreement</u>. This Lease, together
    with the Exhibits, contains all of the agreements of Landlord and Tenant in respect of this Lease and supersedes any previous negotiations. There have been no representations made by Landlord or any of Landlord&#8217;s representatives, or understandings made
    between Landlord and Tenant, other than those set forth in this Lease and the Exhibits. This Lease may not be modified except by a written instrument duly executed by the party to be bound. Landlord and Tenant each represent to the other, that is has
    the individuals executing this Lease have been properly authorized by proper action of the Landlord and Tenant, as the case may be.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.4&#160;&#160; </font>&#160;&#160;&#160;<u>Execution in Counterparts</u>. This Lease may
    be executed in counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same instrument.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.5&#160;&#160;&#160;&#160;&#160; </font><u>Recording</u>. Tenant shall not record this
    Lease, but may record a short form memorandum of this Lease in the form attached hereto as <u>Exhibit D</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.6&#160;&#160; </font>&#160;&#160;&#160;<u>Non-Discrimination</u>. Tenant shall not (and
    Tenant shall not permit any person claiming through or under Tenant to) discriminate against or segregate any person or group of persons on account of race, color, creed, sex, religion, marital status, ancestry, or national origin, whether in the use,
    occupancy, subleasing, transferring, or enjoyment of the Premises, or otherwise.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">46</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.7&#160;&#160;&#160;&#160;&#160; </font><u>Attorneys&#8217; Fees</u>. In any action or
    proceeding that Landlord or Tenant initiates against the other party declaratory or otherwise, arising out of this Lease, the unsuccessful party in such action or proceeding shall reimburse the prevailing party for its costs, including reasonable
    attorneys&#8217; fees (at trial and appellate levels).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.8&#160;&#160; </font>&#160;&#160;&#160;<u>Waiver of Consequential Damages</u>. Except as
    set forth in <u>Section 1.3</u> and <u>Section 3.3</u>, neither Landlord nor Tenant shall be liable to the other for any form of special, indirect, consequential, or punitive damages.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.9&#160;&#160; </font>&#160;&#160;&#160;<u>Tenant Information</u>. Upon Landlord&#8217;s
    request from time to time, Tenant shall provide to Landlord the financial statements for Tenant for its most recent fiscal year and fiscal quarter. Financial statements for each fiscal year shall be prepared and certified by a certified public
    accountant; financial statements for each quarter shall be prepared and certified by Tenant&#8217;s chief financial officer. In addition, if so requested, and provided that Landlord may not require such information more than once in any calendar year except
    where Landlord has reasonable grounds for concern, details of the financial and credit standing and details of the corporate organization of Tenant and any Indemnitor, including copies of financial statements for the last three (3) fiscal years of
    Tenant. If requested by Tenant, such financial statements shall be furnished pursuant to a confidentiality agreement in a form reasonably provided by Landlord for such purpose. The provisions of this Section 10.6.9 shall not apply to Tenant if it is a
    Public Company and its financial statements are publicly available.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif">10.6.10&#160;&#160;&#160;&#160;</font><u>REIT Provisions</u>. Tenant and Landlord intend
    that all amounts payable by Tenant to Landlord shall qualify as &#8220;rents from real property,&#8221; and will otherwise not constitute &#8220;unrelated business taxable income&#8221; or &#8220;impermissible tenant services income,&#8221; all within the meaning of Section 856(d) of the
    Internal Revenue Code of 1986, as amended (the &#8220;<b>Code</b>&#8221;) and the U.S. Department of Treasury Regulations promulgated thereunder (the &#8220;<b>Regulations</b>&#8221;). In the event that Landlord determines that there is any risk that any amount payable under
    this Lease may not qualify as &#8220;rents from real property&#8221; or will otherwise constitute impermissible tenant services income within the meaning of Section 856(d) of the Code and the Regulations, Tenant agrees to (a) cooperate with Landlord by entering
    into such amendment or amendments as Landlord deems necessary to qualify all amounts payable under this Lease as &#8220;rents from real property&#8221; and (b) permit (and, upon request, to acknowledge in writing) an assignment of the obligation to provide certain
    services under the Lease, and, upon request, to enter into direct agreements with the parties furnishing such services (which shall include but not be limited to a taxable REIT subsidiary of Landlord). Notwithstanding the foregoing, Tenant shall not be
    required to take any action pursuant to the preceding sentence (including acknowledging in writing an assignment of services pursuant thereto) if such action would result in (A) Tenant&#8217;s incurring more than de minimis additional liability under this
    Lease or (B) more than a de minimis negative change in the quality or level of Building operations or services rendered to Tenant under this Lease. For the avoidance of doubt, (i) if Tenant does not acknowledge in writing an assignment as described in
    clause (b) above (it being agreed that Tenant shall not unreasonably withhold, condition or delay such acknowledgment so long as the criteria in clauses (A) and (B), above, are satisfied), then Landlord shall not be released from liability under this
    Lease with respect to the services so assigned; and (ii) nothing in this Section 10.6.10 shall limit or otherwise affect Landlord&#8217;s ability to assign its entire interest in this Lease to any party as part of a conveyance of Landlord&#8217;s ownership
    interest in the Building.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 0.5in; text-align: justify">10.7&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Interpretation</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.1&#160;&#160;&#160;&#160;&#160; </font><u>Captions</u>. The captions
    in this Lease are for convenience of reference and shall not define, increase, limit, or describe the scope or intent of any provision of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.2&#160;&#160; </font>&#160;&#160;&#160;<u>Landlord and Tenant</u>. The
    terms &#8220;Tenant&#8221; and &#8220;Landlord&#8221;, and any pronoun used in place thereof, shall indicate and include each of the parties&#8217; and respective successors, executors, administrators, and permitted assigns, according to the context, provided that, for the purposes
    of any provisions indemnifying or waiving claims against, Landlord, the term &#8220;Landlord&#8221; shall also include Landlord&#8217;s present and future investment manager, and property management company, and all of their trustees, directors, officers, partners,
    beneficiaries, principals, members, managers, investors, stockholders, employees, Affiliates, agents, representatives, contractors (and subcontractors of any tier), successors and assigns.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.3&#160;&#160; &#160;&#160;&#160;</font><u>Non-Exclusivity</u>. Whenever
    the words &#8220;including&#8221;, &#8220;include&#8221;, or &#8220;includes&#8221; are used in this Lease, they shall be interpreted in a non-exclusive manner as though the words &#8220;without limitation&#8221; immediately followed the same. Any reference to &#8220;any part&#8221; or &#8220;any portion of&#8221; the
    Premises or any other property shall be construed to refer to all or any part of the same.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.4&#160;&#160; </font>&#160;&#160;&#160;<u>Covenants Independent</u>.
    This Lease shall be construed as though the covenants herein between Landlord and Tenant are independent.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.5&#160;&#160; </font>&#160;&#160;&#160;<u>Joint and Several Liability</u>.
    In any case where either Landlord or Tenant consists of more than one person, the obligations of such party under this Lease shall be joint and several.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif">10.7.6 </font>&#160;&#160;&#160;&#160;&#160;<u>Time of the Essence</u>. Time is
    of the essence of this Lease and all of its provisions.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif">10.7.7 &#160;&#160;&#160;&#160;</font>&#160;<u>Governing Law</u>. This Lease
    shall in all respects be governed by the laws of the State of California without giving effect to the principles of conflicts of law thereof or of any other jurisdiction that would result in the application of the Applicable Laws of any other
    jurisdiction. Tenant&#8217;s obligation to pay Rent shall not be discharged or otherwise affected by any Applicable Law or regulation now or hereafter applicable to the Premises, or any other restriction on Tenant&#8217;s use, or (except as expressly provided in
    this Lease) any Casualty or Taking, or any failure by Landlord to perform any covenant contained herein, or any other occurrence; and no termination or abatement remedy that is not expressly provided for in this Lease for any breach or failure by
    Landlord to perform any obligation under this Lease shall be implied or applicable as a matter of Applicable Law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 1in; margin-bottom: 0pt; text-align: justify; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.8&#160;&#160; &#160;&#160;&#160;</font><u>Successors and Assigns</u>.
    Subject to the provisions of <u>Article 5</u>, the provisions of this Lease shall be binding upon and inure to the benefit of the heirs, successors, executors, administrators, and assigns of Landlord and Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif">10.7.9&#160;&#160; &#160;&#160;&#160;</font><u>Submission</u>. The
    submission of this Lease to Tenant or a summary of some or all of its provisions for examination does not constitute a reservation of or option for the Premises or an offer to lease, and no legal obligations shall arise with respect to the Premises or
    other matters herein unless and until such time as this Lease is executed and delivered by Landlord and Tenant and approved by the holder of any mortgage on the Building having the right to approve this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.8<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Tenant&#8217;s Signage</u>. Tenant shall have the
    right to install such signage at or upon the Premises as permitted by Applicable Laws. Tenant, at its sole expense, shall maintain Tenant&#8217;s Signage in good condition and repair during the Term. Should Tenant&#8217;s Signage require maintenance or repairs as
    determined in Landlord&#8217;s reasonable judgment, Landlord shall have the right to provide notice thereof to Tenant and Tenant shall cause such repairs and/or maintenance to be performed within thirty (30) days after receipt of such notice from Landlord at
    Tenant&#8217;s sole cost and expense. Should Tenant fail to perform such maintenance and repairs within the period described in the immediately preceding sentence, then, in addition to all of Landlord&#8217;s other rights and remedies, Landlord may, but need not,
    perform the required maintenance and repairs, and Tenant shall pay Landlord the cost thereof, plus a fee for Landlord&#8217;s oversight and coordination of such work equal to five percent (5%) of its cost, within thirty (30) days after receipt of Landlord&#8217;s
    request for payment, together with reasonable, supporting backup documentation. Landlord shall have the right to maintain one or more signs at the Premises in a prominent location near the entrance to the Building identifying the property manager and
    the identity of Landlord or its direct or indirect ownership group in a manner similar to that shown on <u>Exhibit G</u> attached, subject to Tenant&#8217;s approval of the size and location of such signage, such approval not to be unreasonably withheld,
    conditioned or delayed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.9<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Choice of Law</u>. This Lease shall be
    governed by the Applicable Laws of the State of California.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.10<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>CASp Inspection</u>. For purposes of Section
    1938(a) of the California Civil Code, Landlord hereby discloses to Tenant, and Tenant hereby acknowledges, that neither the Building nor any portion of the Premises has undergone inspection by a Certified Access Specialist (CASp) (defined by California
    Civil Code Section 55.52). Pursuant to California Civil Code Section 1938, Tenant is hereby notified as follows: &#8220;A Certified Access Specialist (CASp) can inspect the subject premises and determine whether the subject premises comply with all of the
    applicable construction-related accessibility standards under state law. Although state law does not require a CASp inspection of the subject premises, the commercial property owner or lessor may not prohibit the lessee or tenant from obtaining a CASp
    inspection of the subject premises for the occupancy of the lessee or tenant, if requested by lessee or tenant. The parties shall mutually agree on the arrangements for the time and manner of any CASp inspection, the payment of the fee for the CASp
    inspection and the cost of making any repairs necessary to correct violations of construction-related accessibility standards within the premises.&#8221; If Tenant requests to perform a CASp inspection of the Premises, Tenant shall, at its cost, retain a
    CASp approved by Landlord to perform the inspection of the Premises at a time agreed upon by the parties. Tenant shall provide Landlord with a copy of any report or certificate issued by the CASp (the &#8220;<b>CASp Report</b>&#8221;). Landlord and Tenant agree
    that any modifications necessary to correct violations of construction related accessibility standards identified in the CASp Report shall be the responsibility of Tenant. Tenant agrees to keep the information in the CASp Report confidential except as
    necessary for the Tenant to complete such modifications.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">10.11<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font><u>Landlord Access</u>. Landlord, its
    affiliates, and their respective contractors and agents, subject to the terms of this Section 10.11, may, (a) at any and all reasonable times during normal business hours (or during non-business hours, if Landlord so requests and Tenant consents), and
    upon at least two (2) business days&#8217; prior notice (which may be oral or by email to the office manager or other Tenant-designated individual at the Premises; but provided that no time restrictions shall apply or advance notice be required if a bona
    fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry and any oral notice will be followed immediately by email notice as provided above prior to entry), enter the Premises to (i) inspect the same
    and to determine whether Tenant is in compliance with its obligations hereunder, (ii) supply any service Landlord is required to provide hereunder, (iii) alter, improve or repair any portion of the premises under the Companion Lease for which access to
    or through the Premises is reasonably necessary, (iv) post notices of non-responsibility, (v) show the Premises to current and prospective investors, lenders and purchasers, and (vii) show the Premises, other than the Secure Access Areas, during the
    final eighteen (18) months of the Term (provided that Tenant has not timely exercised an Extension Option to extend the Term pursuant to Section 1.4) to prospective tenants, and (b) notwithstanding the foregoing, at any and all reasonable times during
    business and non-business hours and upon at least two (2) business days&#8217; prior notice enter the Premises for the purposes of performing any repairs or maintenance that Landlord is obligated or entitled to perform pursuant to this Lease (provided that
    no time restrictions shall apply if a bona fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry); provided, however, that Landlord shall comply with Tenant&#8217;s reasonable safety procedures and
    protocols with respect to the Premises, and with respect to portions of the Premises (if any) that are reasonably designated in writing by Tenant to Landlord as controlled or having restricted access (the &#8220;<b>Secure Access Areas</b>&#8221;), shall comply
    with Tenant&#8217;s reasonable additional security and safety procedures and protocols related to such portions of the Premises including only entering such designated Secure Access Areas when accompanied by a Tenant representative (provided further, that
    Tenant shall provide a Tenant representative to accompany Landlord upon written request from Landlord at least two (2) business days&#8217; in advance). In no event shall Tenant&#8217;s Base Rent abate as a result of Landlord&#8217;s activities pursuant to this Section;
    provided, however, that all such activities shall be conducted in such a manner so as to cause as little interference to Tenant as is reasonably possible. Landlord shall at all times retain keys, key cards and access codes with which to unlock all of
    the doors in the Premises. Landlord acknowledges that the standard operating procedures set forth on Exhibit J shall apply to the issuance to Landlord of any key cards, electronic keypad codes, or door keys to any Secure Access Areas for any
    unaccompanied access too the Premises by Landlord, provided, however, that Tenant shall identify a single designee to act as Landlord&#8217;s point of contact to administer the requirements of Tenant&#8217;s standard operating procedures on behalf of Landlord and
    that in no event shall any such requirements prohibit Landlord&#8217;s entry into Secure Access Areas (i) in the event of a bona fide emergency with an immediate threat to property damage or personal injury that necessitates immediate entry or (ii) when
    accompanied by a representative of Tenant. If an emergency necessitates immediate access to the Premises, Landlord may use whatever force is necessary to enter the Premises, and any such entry to the Premises shall not constitute a forcible or unlawful
    entry to the Premises, a detainer of the Premises, an eviction of Tenant from the Premises or any portion thereof, or a violation of the provisions of this Section 10.11. Notwithstanding anything herein to the contrary, in the event Tenant notifies
    Landlord within one (1) business day (which may be oral or by email to the Landlord-designated individual) following Landlord&#8217;s request for access that the proposed day and/or time for entry will cause a disruption to a planned event, meeting or other
    programming for Tenant, Landlord and Tenant shall cooperate with one another to identify a better date and/or time Landlord&#8217;s entry of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">ARTICLE 11&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center"><b>TENANT&#8217;S RIGHT OF FIRST OFFER</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 0.5in; text-align: justify">11.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Right of First Offer</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>Notwithstanding anything contained in this Lease
    to the contrary, provided that (i) no Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or its affiliate, if Landlord intends to offer the Premises (or any portion thereof) for sale to an
    unaffiliated third party, Landlord shall promptly notify Tenant of the same in writing (the &#8220;<b>Offer Notice</b>&#8221;) and indicate the terms and conditions upon which Landlord is willing to accept for the sale of the Premises to a third party. Tenant may
    elect to purchase the Premises (or portion thereof) on the terms and conditions set forth in the Offer Notice by notifying Landlord in writing (the &#8220;<b>Election Notice</b>&#8221;) of its election no later than fifteen (15) days after the Offer Notice, which
    notice shall be accompanied by the Option Deposit (defined herein), and the sale of the Premises shall be consummated pursuant to the terms hereof on a date (the &#8220;<b>Closing Date</b>&#8221;) within sixty (60) days after the Election Notice, such date to be
    mutually agreed upon by Landlord or Tenant. In the event of any of the following: (x) Tenant fails to deliver the Election Notice or the Option Deposit to Landlord on or before the expiration of the 15-day period set forth above, (y) Tenant fails to
    close on its acquisition of the Premises on or before the Closing Date, or (z) Landlord provides an Offer Notice to Tenant and Tenant does not exercise its right to purchase the Premises, then in each case Tenant shall be deemed to have waived its
    right to purchase the Premises and thereafter Tenant&#8217;s rights under this Article 11 shall be null and void and of no further force or effect. The term &#8220;<b>Option Deposit</b>&#8221; shall mean the amount of cash deposit required in the Offer Notice or, if no
    cash deposit is specified in the Offer Notice, a sum equal to five percent (5%) of the purchase price for the Premises set forth in the Offer Notice.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 1in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>If the Premises is not sold to Tenant pursuant to
    Section 11.1.1 above, Landlord shall have the right to direct the marketing of the Premises (including the unilateral right to select any broker to be utilized), and to take all actions in furtherance thereof, including, without limitation, the right
    and authority to execute, such agreements, documents, instruments and applications, including a purchase and sale agreement and a deed, assignment of leases, bills of sale and other conveyance documents conveying the Premises (collectively, &#8220;<b>Sale
      Documents</b>&#8221;) as Landlord, may reasonably deem necessary or desirable in order consummate such sale, and, subject to <u>Section 11.1.1</u> above and <u>Section 11.2</u> below, Landlord shall be authorized to accept an offer for the sale of the
    Premises. If Landlord modifies the terms of its offer such that the purchase price is less than ninety-five percent (95%) of the consideration provided in the Offer Notice, then the proposed transaction shall again be subject to Tenant&#8217;s rights under
    this Article 11, and Landlord shall deliver an amended Offer Notice to Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.1.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>Tenant shall, at no material out-of-pocket cost to
    Tenant, reasonably cooperate with Landlord&#8217;s efforts to sell the Premises, including by providing information with respect to the Premises, and by allowing and facilitating physical access to the Premises to prospective purchasers and their lenders and
    consultants, but such cooperation and execution by the Tenant shall not be a condition to the effectiveness of any actions taken by Landlord with respect to such sale or to the effectiveness of Sale Documents.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Tenant&#8217;s Competitors</u>. Provided that (i) no
    Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or an affiliate, and such Tenant remains in possession of the Premises and operating for the Permitted Use, Landlord shall not sell the
    Premises (or any portion thereof, or all or substantially all of Landlord&#8217;s interest therein) or enter into an agreement to that would transfer Landlord&#8217;s interest in the Premises to a Competitor during the Term; provided, however, this Section 11.2
    shall not prohibit Landlord from entering into an agreement to sell or transfer the Premises to a Competitor if the effective date of the transfer would occur after the expiration of the Term. As used herein, &#8220;<b>Competitor</b>&#8221; or &#8220;<b>Competitors</b>&#8221;
    means the companies expressly listed as competitors in Tenant&#8217;s most recent publicly filed Annual Report (10-K); provided, however, (1) such companies shall be directly engaged in the development, manufacturing, or commercializing a medicine or other
    life sciences product, and &#8220;Competitor&#8221; shall not mean any affiliates, investors, parents, or other stake-holders of such companies, and (2) there shall not be more than twenty (20) Competitors at any one time. If Tenant&#8217;s most recent publicly filed
    Annual Report (10-K) includes more than twenty (20) companies that would otherwise be deemed Competitors, only those companies that were previously listed in Tenant&#8217;s Annual Report (10-K) shall be deemed a Competitor unless Tenant provides a written
    notice to Landlord specifying which companies listed in Tenant&#8217;s most recent Annual Report (10-K) shall be included in the list of twenty (20) Competitors for the purposes of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Transfers</u>. Notwithstanding anything to the
    contrary herein, Tenant&#8217;s rights under this Article 11 shall not apply to any transaction that meets at least one of the following criteria:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160; </font>any sale/leaseback transaction made in connection
    with a bona fide financing, provided that the seller/lessee under any such transaction shall be bound by the provisions of this Article 11 at such time, if any, as such seller/lessee reacquires title to the Premises;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>any sale or transfer of the Premises to a
    partnership, corporation, limited liability company, trust or other entity that is under control by, common control with, or controls Landlord or any direct or indirect owner of Landlord, but any such transferee shall hold title subject to Tenant&#8217;s
    rights under this Article 11;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>any transfer in the nature of a financing
    transaction with a financial institution that is made for a bona fide business purpose (i.e., other than in order to allow a transfer of the Premises in avoidance of Tenant&#8217;s rights under this Article 11), including without limitation the granting of,
    foreclosure under, or giving of a deed-in-lieu of foreclosure under, a mortgage or the granting or exercise of any pledge of ownership interests; provided that, following any foreclosure of the Premises, deed in lieu thereof, or similar acquisition of
    title by a mortgagee, lender, or their affiliates, following the first sale of the Premises by such mortgagee, lender or their affiliates, the subsequent Landlord shall be bound by Tenant&#8217;s rights under this Article 11;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>&#160;&#160;any issuance or transfer of a direct or indirect
    interest in Landlord that represents a transfer of less than 80% of such interests (so long as such transfer does not also include the ability to control the day-to-day operations of Landlord); provided that any transferee of direct interests in
    Landlord otherwise described in this Section 11.3.4 is not a Competitor;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.5&#160;&#160;<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; </font>any issuance or transfer of a direct or indirect
    interest in Landlord on a nationally recognized stock exchange; and</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">11.3.6<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>any bona fide portfolio transaction that includes
    at least two other real estate assets (excluding the Premises and, if the Companion Lease is in effect, the Companion Premises) that in the aggregate have rentable space at least equal to 416,000 square feet of rentable space.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.4<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Termination</u>. Upon (x) any sale of the
    Premises, (y) any portfolio transaction sale that includes the Premises, or (z) any foreclosure of a Mortgage on the Premises or conveyance by deed-in-lieu of foreclosure, in each case to a third-party person or entity in accordance with the terms of
    this Article 11, Tenant&#8217;s right of first offer to purchase the Premises under this Article 11 shall forever terminate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">11.5<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Confidentiality</u>. Any Offer Notice and
    information in connection therewith, and any information regarding a sale of the Premises, provided to Tenant by Landlord pursuant to this Article 11 shall be held confidential by Tenant and not disclosed to any third party except as required by law or
    in connection with any dispute between Landlord and Tenant regarding this Article 11 and for disclosures to Tenant&#8217;s legal advisors and third-party consultants to the extent such legal advisors and consultants are reasonably required for Tenant to
    evaluate such information and, in each case, provided that such legal advisors and consultants are made subject to the provisions of this paragraph or are otherwise bound by provisional obligations of confidentiality. Any such information shall be
    returned by Tenant to Landlord if Tenant&#8217;s rights under this Article 11 terminate in accordance with the terms hereof. Nothing in this Section 11.5 shall prevent Tenant from making disclosures required by applicable public company disclosure laws,
    provided, however, such disclosures shall include no more information than what is minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to reasonably approve any disclosure that exceeds what is
    minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to review any disclosure prior to the filing of the same for purposes of confirming compliance with the terms of this sentence, to the extent
    that such review is permitted pursuant to Applicable Law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">ARTICLE 12 <br>
    LIMITATION OF LIABILITY</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: left; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">12.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Landlord&#8217;s Liability</u>. Tenant agrees from
    time to time to look only to Landlord&#8217;s interest in the Premises for satisfaction of any claim against Landlord hereunder or under any other instrument related to the Lease (including any separate agreements among the parties and any notices or
    certificates delivered by Landlord) and not to any other property or assets of Landlord. If Landlord from time to time transfers its interest in the Premises, then from and after each such transfer Tenant shall look solely to the interests in the
    Premises of Landlord&#8217;s transferees for the performance of all of the obligations of Landlord hereunder (or under any related instrument). The obligations of Landlord shall not be binding on any direct or indirect partners (or members, trustees, or
    beneficiaries) of Landlord or of any successor, individually, but only upon Landlord&#8217;s or such successor&#8217;s interest described above. Further, if Landlord is, or one of the parties comprising Landlord is, or the Lease is assigned to, a real estate
    investment trust (&#8220;<b>REIT</b>&#8221;), the parties acknowledge and agree that the obligations of the REIT hereunder and under all documents delivered pursuant hereto (and all documents to which the Lease may be pursuant) or which give effect to, or amend or
    supplement, the terms of the Lease are not personally binding upon any trustee thereof, any registered or beneficial holder of units (a &#8220;<b>Unitholder</b>&#8221;) or any annuitant under a plan of which a Unitholder acts as a trustee or carrier, or any
    officers, employees or agents of the REIT and resort shall not be had to, nor shall recourse or satisfaction be sought from, any of the foregoing or the private property of any of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; margin-left: 0in; text-indent: 0.5in; text-align: justify">12.2 &#160;&#160;&#160;&#160;&#160;&#160;<u>Assignment of Rents</u>.</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.1<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160; </font>With reference to any assignment by Landlord of
    Landlord&#8217;s interest in this Lease, or the rents payable hereunder, conditional in nature or otherwise, which assignment is made to the holder of a mortgage on property that includes the Premises, Tenant agrees that the execution thereof by Landlord,
    and the acceptance thereof by the holder of such mortgage shall never be treated as an assumption by such holder of any of the obligations of Landlord hereunder unless such holder shall, by notice sent to Tenant, specifically otherwise elect and,
    except as aforesaid, such holder shall be treated as having assumed Landlord&#8217;s obligations hereunder only upon foreclosure of such holder&#8217;s mortgage and the taking of possession of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.2<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>In no event shall the acquisition of Landlord&#8217;s
    interest in the Premises by a purchaser that, simultaneously therewith, leases Landlord&#8217;s entire interest in the Premises back to the seller thereof be treated as an assumption by operation of Law or otherwise, of Landlord&#8217;s obligations hereunder, but
    Tenant shall look solely to such seller-lessee, and its successors from time to time in title, for performance of Landlord&#8217;s obligations hereunder. In any such event, this Lease shall be subject and subordinate to the lease to such purchaser. For all
    purposes, such seller-lessee, and its successors in title, shall be the Landlord hereunder unless and until Landlord&#8217;s position shall have been assumed by such purchaser-lessor.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 1in">12.2.3<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160; &#160;&#160;</font>Except as provided in Section 12.2.2, in the event
    of any transfer of title to the Premises by Landlord, the transferring Landlord shall thereafter be entirely freed and relieved from the performance and observance of all covenants and obligations hereunder, and Tenant shall only look to any subsequent
    party becoming Landlord hereunder the same. Tenant hereby agrees to enter into such agreements or instruments as may, from time to time, be requested in confirmation of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">(SIGNATURES APPEAR ON NEXT PAGE)</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-indent: 0.5in; margin-bottom: 0pt; text-align: center">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">54</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"><b>IN WITNESS WHEREOF</b>, the parties hereto have duly executed this Lease on the day and year first above written.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td colspan="2"><b>LANDLORD:</b></td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td style="width: 3%">&#160;</td>
        <td style="width: 47%">&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2"><b>LOTS 21 &amp; 22 OWNER (DE) LLC,</b> a Delaware limited liability company</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td>By:</td>
        <td style="border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td>&#160;</td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 5%">Name:</td>
        <td style="width: 45%; border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 4%">Title:</td>
        <td style="width: 46%; border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 3%">&#160;</td>
        <td style="width: 47%">&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2"><b>TENANT:</b></td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2"><b>IONIS PHARMACEUTICALS, INC.,</b> a Delaware corporation</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td colspan="2">&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top; text-align: left">
        <td>By:</td>
        <td style="border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td>&#160;</td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 5%">Name:</td>
        <td style="width: 45%; border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>

  </table>
  <p style="margin: 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 4%">Title:</td>
        <td style="width: 46%; border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
        <td style="width: 50%">&#160;</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">55</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in">&#160;</p>
  <title></title>
  <p style="margin: 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>SCHEDULE 1</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>EXAMPLE SHOWING CALCULATION OF BASE RENT</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>&#160;</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: bottom">
        <td style="width: 44%; border-top: Black 1pt solid; font-weight: bold; text-align: left">Cost Item</td>
        <td style="width: 18%; border-top: Black 1pt solid; font-weight: bold; text-align: center">Ref</td>
        <td style="width: 20%; border-top: Black 1pt solid; font-weight: bold; text-align: center">Preliminary Estimate</td>
        <td style="width: 18%; border-top: Black 1pt solid; font-weight: bold; text-align: center">$PSF</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: left; padding-left: 0.125in">Land Acquisition</td>
        <td style="vertical-align: top; border-top: Black 1pt solid; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: center">33,000,000</td>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: center">200</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; text-align: left; padding-left: 0.125in">Closing Costs Allocation</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">330,000</td>
        <td style="vertical-align: bottom; text-align: center">2</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="text-align: left; padding-left: 0.125in">Soft Costs</td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">8,352,652</td>
        <td style="text-align: center">51</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; text-align: left; padding-left: 0.125in">Hard Costs</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">94,878,874</td>
        <td style="vertical-align: bottom; text-align: center">576</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; text-align: left; padding-left: 0.125in">Landlord Tenant Improvement Allowance</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">41,208,250</td>
        <td style="vertical-align: bottom; text-align: center">250</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="text-align: left; padding-left: 0.125in">Development Fee<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">3,921,111</td>
        <td style="text-align: center">24</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="text-align: left; padding-left: 0.125in">Oxford Overhead</td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">1,300,000</td>
        <td style="text-align: center">8</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; text-align: left; padding-left: 0.125in">Operating Shortfall</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">2,607,603</td>
        <td style="vertical-align: bottom; text-align: center">16</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; text-align: left; padding-left: 0.125in">Financing Costs</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">12,407,982</td>
        <td style="vertical-align: bottom; text-align: center">75</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="border-top: Black 1pt solid; font-weight: bold; text-align: left">Total Budget</td>
        <td style="border-top: Black 1pt solid; font-weight: bold; text-align: center">(A)</td>
        <td style="border-top: Black 1pt solid; font-weight: bold; text-align: center">198,006,472</td>
        <td style="border-top: Black 1pt solid; font-weight: bold; text-align: center">1,201</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-top: Black 1pt solid; text-align: center" colspan="4">&#160;</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: left; padding-left: 0.125in">Yield-on-Cost</td>
        <td style="vertical-align: bottom; border-top: 1pt solid Black; text-align: center; font-weight: bold;">(B)</td>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: center">6.10%</td>
        <td style="vertical-align: top; border-top: Black 1pt solid; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; text-align: left">
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: left; margin-bottom: 0pt">Annual Rent at Commencement</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: left; margin-bottom: 0pt"></p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: left; margin-bottom: 0pt">Monthly Rent at Commencement</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: left; margin-bottom: 0pt"></p>
        </td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; font-weight: bold; text-align: center">(A * B)<br>
          (A * B)/12</td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center">
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt">12,078,395&#160;</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center">1,006,533</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
        </td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center">
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt">73.28&#160;</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt">6.11</p>
          <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
        </td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="text-align: left; font-size: 10pt">(1<font style="color: #656567">) </font>Calculated based on sum of (a) 3.0% of Hard and Soft Costs, and (b) 1.0% of Tenant Improvement Allowance and assumed lonis spend of $250 PSF</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">56</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>EXHIBIT A</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>LEGAL DESCRIPTION OF THE PREMISES</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Real property in the City of CARLSBAD, County of San Diego, State of California, described as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">LOTS 21 AND 22 OF CARLSBAD TRACT NO. 97-13-03, CARLSBAD OAKS NORTH PHASE 3, IN THE CITY OF CARLSBAD, COUNTY OF SAN DIEGO, STATE OF CALIFORNIA, ACCORDING TO MAP THEREOF NO. 16145, FILED IN
    THE OFFICE OF THE COUNTY RECORDER OF SAN DIEGO COUNTY, OCTOBER 13, 2016 AS DOCUMENT 2016-7000438 OF OFFICIAL RECORDS.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">APN: 209-120-23-00 (Affects: Lot 21) and 209-120-24-00 (Affects: Lot 22)&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">57</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0.1pt">EXHIBIT B</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0.1pt">WORK LETTER</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0.1pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">This Work Letter (this &#8220;<b>Work Letter</b>&#8221;) is made and entered into as of __________ (&#8220;<b>Effective Date</b>&#8221;) and is attached to and made a
    part of that certain Lease by and by and between <b>LOTS 21 &amp; 22 OWNER (DE) LLC</b>, a Delaware limited liability company as landlord (&#8220;<b>Landlord</b>&#8221;) and <b>IONIS GAZELLE, LLC</b>, a Delaware limited liability company as tenant (&#8220;<b>Tenant</b>&#8221;)






    for the development of approximately 8.37 acres (the &#8220;<b>Land</b>&#8221;) known as Lots 21 and 22 with approximately 164,833 gross square feet, which shall be comprised of a three (3) level lab and office building (the &#8220;<b>Building</b>&#8221;), a three (3)
    (inclusive of the rooftop deck) level parking structure (&#8220;<b>Parking Structure</b>&#8221;) and a pedestrian bridge connecting the Building to an adjacent building leased by Tenant from an affiliate of Landlord (the &#8220;<b>Bridge</b>&#8221;). Capitalized terms not
    otherwise defined in this Work Letter shall have the meanings set forth in the Lease. In the event of any conflict between the terms hereof and the terms of the Lease, the terms hereof shall prevail for the purposes of design and construction of the
    Improvements (hereinafter defined).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Permits and Approvals</u>. Prior to the Effective Date, Tenant has
    applied for and obtained (or Landlord has obtained by use of its self-help rights under the PSA, as defined below) the discretionary zoning and planning approvals and approvals by the Architecture Committee under the covenants, conditions and
    restrictions of the Carlsbad Oaks North Business Park Owners Association necessary to obtain a building permit for Landlord&#8217;s Construction Work by right (as identified on <u>Schedule 1</u>, attached, the &#8220;<b>Entitlements</b>&#8221;), and, prior to
    commencement of construction, has obtained or will obtain the other ministerial permits necessary for the development and construction of the Landlord&#8217;s Construction Work (as defined below) (as identified on <u>Schedule 1</u>, attached, the &#8220;<b>Ministerial






      Approvals</b>&#8221;; collectively, together with the Entitlements, the &#8220;<b>Permits and Approvals</b>&#8221;), which Permits and Approvals Tenant acknowledges and agrees are all of the permits, licenses, and approvals necessary for the commencement of
    construction of all of the Landlord&#8217;s Construction Work, provided, however, that following the Effective Date, to the extent Tenant has not yet prepared and/or submitted applications for Ministerial Permits in accordance with the Development Schedule,
    Landlord (or General Contractor) shall be responsible for preparing and/or submitting such Ministerial Permits. The parties acknowledge that certain Permits and Approvals are necessary solely for commencing a particular aspect of the Landlord&#8217;s
    Construction Work (e.g., the grading permit and lot line adjustment between lots 21 &amp; 22). The parties further acknowledge that, following the commencement of vertical construction of the Building and Parking Structure, certain ministerial permits
    will be obtained by Landlord (or the General Contractor) in the ordinary course as normally obtained in the course of construction. Tenant shall use diligent, best efforts to pursue the Entitlements on or before the Outside Satisfaction Date as defined
    in (and subject to extensions expressly permitted under) that certain Purchase and Sale Agreement dated October <b>[To be filled in based on final executed version of PSA:]</b> __________, 2022, by and between Tenant and an affiliate of Landlord (the
    &#8220;<b>PSA</b>&#8221;). Tenant shall provide Landlord with updates regarding the status of the Permits and Approvals from time to time (and in any event no less often than once per month) and otherwise upon the written request of Landlord. Tenant shall not
    amend or modify the Entitlements, or submit any new applications for Entitlements, without the prior written consent of Landlord, and, in any event, the final Entitlements shall be subject to the final written approval of Landlord, in each case such
    consent and approval not to be unreasonably withheld, conditioned, or delayed, provided that it shall be reasonable for Landlord to disapprove of the Entitlements, amendments to them, or applications for any new Entitlements for Landlord&#8217;s Construction
    Work, if they (a) contain conditions (i) the cost of which are not (A) includable within the Construction Costs (unless Tenant agrees in writing to pay such costs directly and such Entitlements, amendments, or applications for new Entitlements
    otherwise comply with the provisions of clause (ii)) or (B) otherwise the responsibility of Tenant pursuant to the terms of the Lease (unless Tenant agrees in writing to perform the same and such Entitlements, amendments, or applications for new
    Entitlements otherwise comply with the provisions of clause (ii)), or (ii) that are not customary for similar first class lab and office projects in the applicable leasing market (including without limitation with respect to costs or obligations
    resulting from the same that are recurring beyond the termination or earlier expiration of the Term), or (b) are inconsistent with the Approved Concept Plans (as defined below).</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The Permits and Approvals shall provide for (a), at a minimum, as-of-right use of the Premises for the Permitted Use, (b) improvements with a lab
    to office ratio of no less than 35% to 65%, the calculation of which shall be made in good faith by Landlord and Tenant in consultation with the Architect (with any dispute being resolved pursuant to Article 13, below), (c) at least 164,833 square feet
    of gross floor area (as measured by the applicable zoning codes and ordinances), (d) no fewer than 426 parking stalls, floor-to-floor heights of at least 16 feet, (e) a floor load of at least 125 pounds per square foot live load, 15 pounds per square
    foot dead load and, in any event, on areas of the roof within areas of mechanical screening or otherwise intended for mechanical equipment installations, at least 150 pounds per square foot, (f) vertical MEP infrastructure sufficient to support a lab
    to office ratio of at least 50% to 50% (incorporating the minimum standards set forth on <u>Schedule 8</u>, attached), (g) building construction type of II-B, (h) MEP capacities consistent with <u>Schedule 8</u> and MEP infrastructure consistent with
    the allocation of responsibility attached as part of <u>Schedule 2</u>, and (j) otherwise be consistent with first class life sciences use, generally (the &#8220;<b>Fundamental Requirements</b>&#8221;). Landlord shall approve or provide detailed objections to the
    Entitlements within ten (10) business days of its receipt of the same. If Landlord fails to respond within such ten (10) business day period, Tenant may provide a written reminder notice to Landlord. Landlord&#8217;s failure to respond to such reminder
    notice within three (3) business days after delivery of such notice shall be deemed to be Landlord&#8217;s approval of the Entitlements. Prior to making any material submission to a permitting or other governmental authority, committee, association, or other
    regulatory committee, agency or governing body having jurisdiction over the over the Landlord&#8217;s Construction Work (collectively, &#8220;<b>governmental authorities</b>&#8221;), Tenant shall give the Landlord the opportunity to review and comment on the same, and
    Tenant shall give Landlord reasonable prior notice of any material meetings, hearings, or conversations with governmental authorities related the Permits and Approvals and give Landlord the reasonable opportunity to participate in the same.
    Furthermore, to the extent Tenant is responsible for Ministerial Approvals pursuant to this Section 1, Tenant shall submit such applications for Ministerial Approvals to Landlord for its review and comment prior to Tenant submitting the same to the
    applicable governmental authorities, but such review by Landlord is solely for the purpose of confirming that such applications are consistent with the terms and conditions of this Work Letter. Tenant shall cooperate with Landlord as reasonably
    required to facilitate obtaining the Ministerial Approvals in an orderly and timely manner to the extent the same have not been obtained by Tenant prior to the Effective Date, including by providing Landlord with such information as is necessary with
    respect to prior and pending applications.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Design of the Landlord&#8217;s Construction Work</u>. Prior to the
    Effective Date, Tenant has caused the Architect to prepare, and the Landlord and Tenant have approved, the conceptual plans and the allocation of responsibility for the Landlord&#8217;s Construction Work as further described on <u>Schedule 2</u>, attached
    (collectively, the &#8220;<b>Approved Concept Plans</b>&#8221;). The Approved Concept Plans will be developed into Approved Core and Shell Plans as further provided in Section 5.2, below.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">3.<font style="font-family: Times New Roman, Times, Serif">&#160; &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Construction</u>. Promptly following the date on which
    the Permits and Approvals have been received and are no longer subject to any potential appeal or challenge and the execution of the GMP Contract as set forth in Section 4.3 below (but in no event prior to the Effective Date), or on such earlier date
    as Landlord may elect in its discretion, Landlord shall cause the General Contractor (hereinafter defined) to commence and diligently prosecute the construction of the shell and core of the Building to completion pursuant to the Approved Shell and Core
    Plans (the <i>&#8220;</i><b>Shell and Core</b>&#8221;), in accordance with the terms and conditions set forth in this Work Letter subject only to Shell and Core Permitted Changes and any other changes authorized pursuant to this Work Letter (all such
    construction, the &#8220;<b>Landlord&#8217;s Construction Work</b>&#8221;). Tenant shall construct the tenant improvements in the Building pursuant to the Approved TI Plans (the &#8220;<b>Tenant Improvements</b>&#8221;) as further provided below<b><i>.</i></b> The Landlord&#8217;s
    Construction Work, together with the Tenant Improvements shall collectively be referred to herein as the &#8220;<b>Building Improvements</b>&#8221;<b><i>. </i></b>Landlord&#8217;s Construction Work shall be constructed in a good and workmanlike manner, and in
    accordance with Applicable Laws (subject only to such incomplete work as will not materially adversely impact Tenant&#8217;s continuous and uninterrupted use of the Premises for Tenant&#8217;s Permitted Use). The allocation of responsibility for completion of the
    Building Improvements is included as part of <u>Schedule 2</u>.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Substantial Completion of Landlord&#8217;s Construction Work</u>.
    Landlord&#8217;s Construction Work shall be deemed &#8220;<b>Substantially Complete</b>&#8221; or there shall be &#8220;<b>Substantial Completion</b>&#8221; at such time as (a) Landlord has received an AIA form certificate from the Architect confirming that the Landlord&#8217;s
    Construction Work is substantially complete substantially in accordance with the Approved Shell and Core Plans, other than seasonal items such as balancing and landscaping, and other Punchlist Items (as defined below), and (b) all certifications and
    approvals with respect to the completion of the Landlord&#8217;s Construction Work that may be required from any governmental authority to permit occupancy of the Premises for the Permitted Use, generally (as opposed to Tenant&#8217;s use, specifically) have been
    obtained by Landlord (to the extent they may be obtained prior to the completion of the Tenant Improvements). The date on which Landlord&#8217;s Construction Work is deemed Substantially Complete pursuant to the foregoing shall be referred to herein as the &#8220;<b>Substantial






      Completion Date.</b>&#8221; As used herein, the &#8220;<b>Delivery Date</b>&#8221; means the date (i) the Landlord&#8217;s Construction Work is in the condition required by <u>Schedule 7</u> (the &#8220;<b>Delivery Condition</b>&#8221;), and (ii) Landlord has provided Tenant with
    reasonably continuous and uninterrupted access to the Project for the construction of Tenant Improvements, subject to the reasonable requirements necessary for, and established by, Landlord&#8217;s General Contractor to allow it to obtain Substantial
    Completion, complete the Punchlist Items and exercise any of its other rights or obligations under this Work Letter and the Lease within the time periods set forth herein.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">On a date or dates reasonably specified by Landlord (but not later than five (5) business days following Substantial Completion of the Landlord&#8217;s
    Construction Work), Landlord and Tenant and each of their architects shall inspect the Landlord&#8217;s Construction Work for the purpose of preparing a list of the punchlist type items, and any items of a seasonal nature such as balancing and landscaping,
    then remaining to be completed for the Landlord&#8217;s Construction Work (the items on such list being referred to as &#8220;<b>Punchlist Items</b>&#8221;). Landlord shall, within ten (10) business days after the date of such inspection, submit a final punchlist to
    Tenant, and Tenant shall sign and return the final punchlist to Landlord within five (5) business days of Landlord&#8217;s delivery of such final punchlist to Tenant (or, if earlier, by the day before Tenant takes occupancy of the Premises for the Permitted
    Use), noting any items that Tenant reasonably believes should be added thereto. Items shall not be added to the final punchlist by Tenant after it is delivered to Landlord and the expiration of such five (5) business day period. If the final punchlist
    is not executed by Tenant and returned to Landlord within such five (5) business day period, then Tenant shall be deemed to have accepted the final punchlist as submitted to Tenant by Landlord without modification and, except as set forth on the final
    punchlist, Landlord shall have no further obligation to cause any other Landlord&#8217;s Construction Work to be completed. With respect to items on the final punchlist not in dispute, Landlord shall cause such items to be completed as soon as reasonably
    practicable in a diligent manner during regular business hours, but in a manner that will seek to minimize interruption of Tenant&#8217;s construction of the Tenant Improvements. In any event, Landlord shall use commercially reasonable efforts to complete
    all punchlist work within 60 days (or such longer period as is reasonably required with respect to applicable items), other than matters that cannot be completed owing to their seasonal nature (which shall be completed as soon as reasonably practicable
    in a diligent manner), and subject to extension for Force Majeure and Tenant Delays. With respect to any disputed final punchlist items, Landlord shall cause such items to be completed in like manner, but Landlord may nevertheless reserve Landlord&#8217;s
    rights to require Tenant to pay the costs therefor as Construction Costs. In the event of a dispute between Landlord and Tenant over Punchlist Items, the parties shall submit such dispute to resolution pursuant to Section 13, below.&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Schedule and Budget</u>. As of the date hereof, Landlord and
    Tenant estimate that (a) the Delivery Date will occur on or before ___________ <b>[NTD: insert the date that is 18 months following the Effective Date at execution]</b> (the &#8220;<b>Target Delivery Date</b>&#8221;), and (b) the Substantial Completion Date of
    Landlord&#8217;s Construction Work will occur on or before _______________ <b>[NTD: insert the date that is 28 months following the Effective Date at execution]</b> (the &#8220;<b>Target Substantial Completion Date</b>&#8221;). The final GMP agreement with the
    Contractor shall set forth an updated, estimated Delivery Date (the &#8220;<b>Estimated Delivery Condition Date</b>&#8221;) and Substantial Completion Date (the &#8220;<b>Estimated Substantial Completion Date</b>&#8221;) based on the initial construction of the Landlord&#8217;s
    Construction Work. If Landlord reasonably believes the costs and expenses of achieving Substantial Completion of Landlord&#8217;s Construction Work will exceed the contemplated costs and expenses thereof as set forth in the Budget, then Landlord will
    promptly notify Tenant&#8217;s Authorized Representative (by telephone, fax, email, or letter) thereof. All books and records for the Landlord&#8217;s Construction Work will be made available to Tenant on an &#8220;open book&#8221; basis (and Landlord&#8217;s contract with the
    General Contractor shall require that the General Contractor shall also make available all of its books and records on the same &#8220;open book&#8221; basis, and, in coordination with the Landlord&#8217;s final closeout of the construction contract with the General
    Contractor, Tenant may reasonably request that Landlord enforce its rights to audit the General Contractor&#8217;s books and records to the full extent allowed by the Landlord&#8217;s contract with the General Contractor, the costs of which audit shall be included
    in Construction Costs as a soft cost). Landlord&#8217;s contract with the General Contractor for the Landlord&#8217;s Construction Work shall be substantially in the form submitted to Tenant by e-mail delivery from Geoff Howell of DLA Piper LLP (US) to David
    Crawford of Cooley LLP and Mallorie Klemens of Ionis Pharmaceuticals, Inc. on August 22, 2022 and otherwise subject to Tenant&#8217;s review and comment. Tenant shall have five (5) business days to review and reasonably comment on the final form of
    construction contract after delivery to Tenant. If Tenant fails to respond within such five (5) business day period, Landlord may provide a written reminder notice to Tenant. Tenant&#8217;s failure to respond to such reminder notice within two (2) business
    days after delivery of such notice shall be deemed to be a waiver of Tenant&#8217;s right to comment.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Construction Costs</u>. Subject to the terms and provisions of
    this Work Letter, Landlord shall pay the costs to construct the Landlord&#8217;s Construction Work in accordance with this Work Letter. As further provided in the definition of Base Rent within the Basic Lease Information section of the Lease, the Base Rent
    for the Premises shall be determined based on the costs of Landlord to acquire, design, construct, finance, and otherwise develop the Landlord&#8217;s Construction Work (&#8220;<b>Construction Costs</b>&#8221;) with a return-on-cost interest rate of 6.35%. Construction
    Costs include the costs and expenses of (a) Landlord&#8217;s acquisition of the Land, including all closing costs and expenses thereof, (b) reimbursements to Tenant for the TI Allowance (hereinafter defined), (c) the General Contractor and other contractors
    and subcontractors, (d) space planning, architectural services, engineering and other related services, (e) building and other permits and other taxes, fees, charges and levies by any governmental authority for the entitlements (including without
    limitation pursuant to the Permits and Approvals) or for inspections of the Building Improvements, <font style="font-size: 10pt">(f) </font>labor, material, buildings, building systems, equipment, fixtures, additions and decorations, (g) all Taxes
    assessed or imposed and other carrying costs (including interest on debt) for the period from the Effective Date through the Commencement Date, (h) any association fees, (i) all utilities and other out-of-pocket operating costs necessary for
    development and construction, or deficiencies necessary to be paid in order to reconstruct the Landlord&#8217;s Construction Work following any damage or destruction that occurs prior to the Lease Commencement Date, (j) insurance costs payable to the General
    Contractor and any other insurance obtained by Landlord pursuant to the terms of this Work Letter or otherwise required by any lender, (k) legal fees incurred in connection with the Landlord&#8217;s Construction Work; (l) any costs incurred with respect to
    off-site improvements and mitigation such as traffic improvements, sidewalk improvements, and the like; (m) so-called linkage fees and other fees and payments in the nature of mitigation for project impacts as required by Applicable Law or the Permits
    and Approvals, (n) utility connection fees and deposits, (o) off-site improvements required by Permits and Approvals or to complete the Landlord&#8217;s Construction Work in accordance with the Approved Core and Shell Plans, (p) pre-construction fees and
    payments to the General Contractor and other consultants, including any so-called design-assist fees and payments to subcontractors, (q) costs (including interests and fees thereon) incurred by Landlord or any holder of a direct or indirect interest in
    Landlord in connection with obtaining, negotiating and closing the financing of the acquisition and development of the Premises or the Landlord&#8217;s obligations hereunder (including without limitation any construction loan for the Landlord&#8217;s Construction
    Work), (r) any sales and use taxes on materials included within the Landlord&#8217;s Construction Work, (s) the Developer Fee (as defined below), (t) costs to remove, store, remediate, and otherwise handle any Hazardous Materials, (u) reasonably allocated
    costs of the gross salary and wages or pro rata share thereof, federal and state unemployment taxes, social security taxes, group medical and health insurance premiums, worker&#8217;s compensation insurance and other benefits of Landlord and its affiliates
    engaged in the design, construction, financing, and development of the Landlord&#8217;s Construction Work, not to exceed $1,300,000.00 unless resulting from unusually frequent (when judged in accordance with industry custom and practice) change requests,
    unusually frequent (when judged in accordance with industry custom and practice) requests for information, or other acts or omissions of Tenant, Tenant Delays, Shell and Core Tenant Change Order Requests, or delays in the Landlord&#8217;s Construction Work
    caused by Force Majeure, (v) costs to complete work and enforce warranties and indemnities during the Corrective Period (as defined below), and (w) any other costs and expenses necessary for the acquisition, design, development, financing, and
    construction of the Project as determined by Landlord in its reasonable discretion. Construction Costs shall not include any &#8220;project management&#8221; fees payable to Landlord or its affiliates, other than the Developer Fee, and Landlord acknowledges that
    it shall not include a third-party project management consultant in addition to the general contractor as part of Construction Costs. For purposes of this Lease, any funds delivered by Landlord to pay any Construction Costs shall be deemed to
    constitute &#8220;<b>Disbursements</b>&#8221;<b><i>,</i></b> and &#8220;<b>Aggregate Disbursements</b>&#8221; will mean the aggregate amount of funds disbursed by Landlord for the Landlord&#8217;s Costs. To the extent that Tenant has paid or does pay any design or pre-development
    costs directly prior to the Effective Date that would otherwise be an eligible Construction Cost if incurred by Landlord pursuant to this paragraph, such cost shall not be a Construction Cost or otherwise included in the determination of Base Rent. For
    purposes of clarity, it is acknowledged and agreed that Landlord shall (by assumption from Tenant in accordance with this Work Letter or directly) hold all contracts for the design and construction of the Landlord&#8217;s Construction Work from and after the
    Effective Date, and Tenant shall hold all contracts for the design and construction of the Tenant Improvements.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;</font>For a period commencing, and not to exceed, sixty (60) days prior to the
    occurrence of Delivery Condition for the Premises, Tenant shall have the right, upon at least seventy-two (72) hours&#8217; prior written notice via e-mail to Landlord&#8217;s Authorized Representatives, to commence the Tenant Improvements and prosecute the same
    on a schedule to be mutually agreed upon with Landlord and the General Contractor (the &#8220;<b>Early Access Schedule</b>&#8221;) subject to Landlord&#8217;s and the General Contractor&#8217;s reasonable security and safety precautions; <u>provided</u>, however, that prior
    to any such entry, Tenant shall furnish to Landlord evidence reasonably satisfactory to Landlord in advance that insurance coverages required of Tenant under the provisions of <u>Section 8.3</u>, below are in effect. Such entry shall be at Tenant&#8217;s
    sole risk and subject to all the terms and conditions of the Lease, except for the payment of Rent. In the course of such entry, Tenant and its contractors shall not interfere with or delay the occurrence of Delivery Condition or Landlord&#8217;s completion
    of the Landlord&#8217;s Construction Work. Tenant and any Tenant contractor shall not damage, the Landlord&#8217;s Construction Work. Tenant shall be responsible for the costs to repair any Landlord&#8217;s Construction Work to the extent damaged by Tenant&#8217;s contractors
    during the early access period. Following the Effective Date, Landlord and Tenant shall review the Early Access Schedule monthly with the General Contractor to determine with the General Contractor whether updates are needed to reflect the actual
    progress of the Landlord&#8217;s Construction Work (e.g., including to allow access on an earlier date than originally set forth in the Early Access Schedule if Landlord&#8217;s Construction Work is ahead of schedule).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Any requirements of any such Tenant contractor for services from Landlord or the General Contractor, such as hoisting, electrical or mechanical
    needs, shall be paid for by Tenant and arranged between such Tenant contractor and Landlord or Landlord&#8217;s Contractor. Should the Tenant Improvements depend on the installed field conditions of any item of Landlord&#8217;s Construction Work, such Tenant
    contractor shall ascertain such field conditions after installation of such item of Landlord&#8217;s Construction Work. Neither Landlord nor the General Contractor shall be required or obliged to alter the method, time or manner for performing Landlord&#8217;s
    Construction Work on account of the Tenant Improvements, but Landlord&#8217;s General Contractor shall cooperate with Tenant to allow Tenant access to prosecute its work in accordance with the Early Access Schedule. Tenant shall cause each Tenant contractor
    performing Tenant Improvements on the Premises prior to the occurrence of Delivery Condition to substantially clean up regularly and remove its debris from the Premises and Building to the extent reasonably required by the Landlord&#8217;s General
    Contractor.</p>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 36pt">4.</td>
        <td style="text-align: justify"><u>General Requirements</u>.</td>
      </tr>

  </table>
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      <tr style="vertical-align: top">
        <td style="width: 0.5in"></td>
        <td style="width: 36pt">4.1.</td>
        <td style="text-align: justify"><u>Authorized Representatives</u>.</td>
      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Landlord designates, as Landlord&#8217;s authorized representative (&#8220;<b>Landlord&#8217;s






      Authorized Representative</b>&#8221;), Michael Haverty (e-mail: mhaverty@oxfordproperties.com, phone: 857-305-8743) as the person authorized to initial plans, drawings, change orders, and provide consents and approvals pursuant to this Work Letter. Tenant
    shall not be obligated to respond to or act upon any such item until such item has been initialed or signed (as applicable) by the appropriate Landlord&#8217;s Authorized Representative. Landlord may change Landlord&#8217;s Authorized Representative upon one (1)
    business day&#8217;s prior written notice to Tenant. Deliveries to Landlord&#8217;s Authorized Representative by e-mail will be sufficient for purposes of delivery of notices and submissions required under this Work Letter, provided that an e-mail delivery made
    after 5 p.m. shall be treated as having been delivered on the next business day.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in"><font style="font-size: 10pt">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant designates Wayne Sanders
      (e-mail:</font> <font style="font-size: 10pt">[***],</font> <font style="font-size: 10pt">phone: [***]) (&#8220;<b>Tenant&#8217;s Authorized Representative</b>&#8221;) as the person authorized to initial all plans, drawings, change orders and provide consent and
      approvals pursuant to this Work Letter. Landlord shall not be obligated to respond to or act upon any such item until such item has been initialed or signed (as applicable) by Tenant&#8217;s Authorized Representative. Tenant may change Tenant&#8217;s Authorized
      Representative upon one (1) business day&#8217;s prior written notice to Landlord. Deliveries to Tenant&#8217;s Authorized Representative by e-mail will be sufficient for purposes of delivery of notices and submissions required under this Work Letter, provided
      that an e-mail delivery made after 5 p.m. shall be treated as having been delivered on the next business day.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Architects, Contractors and Consultants</u>. The architect,
    engineering consultants, general contractor and major subcontractors responsible for the design and construction of the Landlord&#8217;s Construction Work shall be selected by Landlord and approved by Tenant, which approval Tenant shall not unreasonably
    withhold, condition or delay. Landlord&#8217;s request for approval of any design or construction professional shall be approved or disapproved by Tenant within five (5) business days after delivery to Tenant. If Tenant fails to respond within such five (5)
    business day period, Landlord shall provide a written reminder notice to Tenant. Tenant&#8217;s failure to respond to such reminder notice within three (3) business days after delivery of such notice shall be deemed approval by Tenant of the applicable
    consultant. The parties acknowledge that DG Architects, Inc., dba DGA is approved as the architect, Spurlok is approved as the landscape architect, and EXP (mechanical, electrical and plumbing engineering, inclusive of Fire Alarm and Fire Sprinkler
    Basis of Design), KPFF (structural engineering), Pasco, Laret Suiter &amp; Associates (civil engineering), Waveguide (acoustics/vibration consultant), Forsyth Consulting (building envelope consulting and waterproofing) are approved as engineers and
    consultants, and BNBuilders is approved as General Contractor. Except as pre-approved in this Section 4.2, Tenant may refuse to use any architects, consultants, contractors, subcontractors or material suppliers that Tenant reasonably believes could
    cause labor disharmony during the construction of the Tenant Improvements. The approved architect is referred to herein as the &#8220;<b>Architect</b>&#8221;. Tenant shall enter into an architect&#8217;s agreement with Architect (the &#8220;<b>Architect&#8217;s Contract</b>&#8221;) on a
    form provided by Landlord and approved by Landlord. Tenant shall use diligent, good faith efforts to enter into the Architect&#8217;s Contract on or before November 1, 2022, and in any event shall enter into the Architect&#8217;s Contract prior to the submission
    of schematic design plans to Landlord for its review. As of the Effective Date, Landlord shall assume the Architect&#8217;s Contract. Prior to the Effective Date, Tenant shall not modify or amend the Architect&#8217;s Contract or approve any changes in the
    personnel providing services under the Architect&#8217;s Contract without the prior consent of Landlord, which may be withheld in its sole discretion, and Tenant shall copy Landlord on all written communications with, and submissions to, the Architect.
    Landlord acknowledges that Tenant may hire, at its sole cost (subject to reimbursement as a soft cost out of the TI Allowance), an &#8220;owner&#8217;s representative&#8221; in connection with the Project (a &#8220;<b>Project Manager</b>&#8221;), which Project Manager shall be
    reasonably approved by Landlord and be entitled to participate in meetings and receive any information to which Tenant is entitled under this Work Letter. Landlord acknowledges that it has approved Project Management Advisors, Inc. dba PMA as Tenant&#8217;s
    Project Manager. The &#8220;<b>General Contractor</b>&#8221; for the Landlord&#8217;s Construction Work means BNBuilders (or such other general contractor as may be proposed by either party and approved by the other in writing, such approval not to be unreasonably
    withheld, conditioned, or delayed), the parties acknowledging that such selection took place prior to the Effective Date through a collaborative process based on Tenant&#8217;s request for proposal submitted to the General Contractor candidates, a copy of
    which has been provided to Landlord. Tenant provided Landlord with copies of responses to the request for proposal as well as all material communications between Tenant and any general contractor candidates. As used in this Work Letter, <b>&#8220;significant






      subcontractors and material suppliers&#8221; </b>means those subcontractors and suppliers (including the General Contractor, with respect to any self-performed work) that the parties agree fall within the category of &#8220;material&#8221; based on the final list of
    trades needed to bid on the Landlord&#8217;s Construction Work, as reasonably agreed to by the parties.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font>Landlord shall endeavor to cause Tenant to be designated as a third
    party beneficiary with respect to each warranty and/or indemnity with respect to the Landlord&#8217;s Construction Work that is made by any &#8220;significant subcontractors and material suppliers&#8221; against which Landlord is able to exercise remedies pursuant to a
    contractual right ( each, a &#8220;<b>Material Contractor</b>&#8221;<b>, </b>and each such warranty/indemnity, a &#8220;<b>Third Party Beneficiary Warranty</b>&#8221;<b>); </b>provided, however, that it shall not be a default of Landlord hereunder if Landlord is unable to
    do so. Tenant shall not exercise its rights with respect to any Third Party Beneficiary Warranty until Substantial Completion has occurred and then only if (a) Tenant identifies any part of the Landlord&#8217;s Construction Work that violates such Third
    Party Beneficiary Warranty (a &#8220;<b>Warranty Issue</b>&#8221;<i>), </i>(b) Tenant provides Landlord with written notice of any Warranty Issue, (c) the GMP Contract does not prohibit Landlord as the owner or Tenant as the third party beneficiary from
    exercising its rights with respect to such warranty/indemnity, and (d) either (i) within fifteen (15) business days after receiving such notice from Tenant, Landlord has not requested that the respective Material Contractor address such Warranty Issue,
    or (ii) Landlord fails to diligently endeavor to cause the Material Contractor to address such Warranty Issue (the parties acknowledging that, from and after the Corrective Period (as defined below), Landlord has no obligation to pursue any such
    Warranty Issue). Following the Corrective Period, Landlord shall assign all warranties and indemnities for the Landlord&#8217;s Construction Work to Tenant, to the extent assignable, and, whether or not assignable, shall cooperate with Tenant, at Tenant&#8217;s
    sole cost, to the extent necessary in pursuing any warranty or indemnity claim under the third-party contracts for the Landlord&#8217;s Construction Work. The provisions of this paragraph shall be the Tenant&#8217;s sole remedy in the event of any defect in the
    Landlord&#8217;s Construction Work.&#160;</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>GMP Contract</u>. Following the completion of the Approved Core and
    Shell Plans, Landlord shall cause the General Contractor to solicit bids from at least three subcontractors for each significant subcontract and material supplier (unless fewer than three qualified bidders are available) and shall provide to, and
    review the bids with, Tenant. In the event that the General Contractor desires to self-perform a significant subcontract scope of work, either Landlord shall require the General Contractor to obtain at least two subcontractor bids for each trade to be
    self- performed, or Landlord shall engage a third-party cost estimator (as a Construction Cost) to provide an estimate of the same scope of work, and cause such cost estimator and General Contractor to reconcile estimates within +/-5% prior to
    approving the General Contractor&#8217;s bid. Landlord shall select the lowest qualified bid unless otherwise instructed by Tenant. Landlord covenants that it will, within thirty (30) days following the completion of bidding, enter into a guaranteed maximum
    price contract between Landlord and General Contractor, which shall provide for the one hundred percent (100%) lien-free completion of the Landlord&#8217;s Construction Work, provide for a correction period for defective work of at least twelve (12) (and not
    more than twenty-four (24)) months, and be based on the final bids and otherwise approved terms of the form of construction contract ((the &#8220;<b>GMP Contract</b>&#8221;). The GMP Contract shall contain a complete line item budget to complete the Landlord&#8217;s
    Construction Work in a manner consistent with similar projects. The parties acknowledge that certain long lead packages may be bid and procured separately by Landlord prior to the execution of the GMP Contract. The parties further acknowledge that it
    may be prudent, on the advice of the General Contractor or any other consultant providing pre-construction services, to procure some long lead items contained within the Landlord&#8217;s Construction Work prior the execution of the GMP Contract or to place
    deposits for the acquisition of the same, in each case as a means to mitigate against potential supply chain issues during construction. The parties shall collaborate and cooperate in discussing opportunities for such mitigation. In connection with any
    agreement to spend such amounts prior to the Effective Date, the parties shall agree on how such sums shall be treated for the purposes of Construction Costs (with the understanding that amounts spent by Landlord on any such items shall be considered
    part of Construction Costs, Landlord having no obligation to incur any such costs prior to the Effective Date). The parties further acknowledge that the GMP Contract shall reflect strategies developed with the General Contractor to mitigate against
    risks of supply chain delays; Landlord shall use reasonable efforts, in collaboration with Tenant, to minimize the right of the General Contractor under the GC Contract to claim extensions for Force Majeure resulting from supply chain delays,
    consistent with similar projects in the same market.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.5.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Schedule</u>. The currently anticipated schedule for the
    development, and completion of the Landlord&#8217;s Construction Work is attached hereto as <u>Schedule 3</u> to the Work Letter (the &#8220;<b>Schedule</b>&#8221;). Following the Effective Date, the Landlord shall update the Schedule from time to time to reflect the
    actual status of the Landlord&#8217;s Construction Work. Landlord will provide Tenant with regular updates to the Schedule; provided at a minimum, Landlord shall provide Tenant with a monthly updated Schedule and a reconciliation of the actual progress of
    Landlord&#8217;s Construction Work against the Schedule. Landlord shall use commercially reasonable efforts to complete the Landlord&#8217;s Construction Work in accordance with the Schedule, but Tenant acknowledges that such Schedule is subject to change from
    time to time to reflect the actual progress of the Landlord&#8217;s Construction Work and that failure to comply with the same shall not result in a default under this Lease. Following the commencement of construction, Landlord shall hold weekly a
    construction meeting that includes Tenant&#8217;s Project Manager, the General Contractor, and the Architect.&#160;</p>
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  </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">5.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Shell and Core</u>. Landlord&#8217;s Construction Work related to the
    Shell and Core shall be performed by Landlord at Landlord&#8217;s sole cost and expense substantially in accordance with the Approved Shell and Core Plans, subject only to changes made in accordance with this Work Letter.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">5.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Approved Design Development Plans</u>. As noted above, the parties
    have approved the Approved Concept Plans. Prior to the Effective Date, Landlord acknowledges that Tenant shall have the right to make changes to the Approved Concept Plans as required to comply with the requirements of the City of Carlsbad, subject to
    Landlord&#8217;s reasonable approval, such approval not to be unreasonably withheld, conditioned, or delayed (it being reasonable for Landlord to disapprove of such changes if such change will result in the Landlord&#8217;s Construction Work not complying with the
    Fundamental Requirements). Once approved, any such change shall be incorporated into the Approved Concept Plans by the Architect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">5.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Approved Shell and Core Plans</u>. Prior to the Effective Date, and
    in any event no later than October 17, 2022, Tenant shall cause the Architect to develop full schematic design documents for the entire Premises that are consistent with the Approved Concept Plans, which schematic design documents shall be subject to
    Landlord&#8217;s written approval, such approval not to be unreasonably withheld, conditioned or delayed provided that the same are consistent with the Concept Plans, the requirements of the Permits and Approvals, and the Fundamental Requirements, and
    achievement of Delivery Condition and Substantial Completion by the Target Delivery Condition Date and Target Substantial Completion Date, respectively (as approved, the &#8220;<b>Approved Schematic Plans</b>&#8221;). Following the Effective Date, Landlord shall
    cause the Architect to prepare design development documents and final 100% construction documents for the Landlord&#8217;s Construction Work that (c) are consistent with and are logical evolutions of the Approved Schematic Plans or reasonably inferable
    therefrom, and (b) incorporate any Shell and Core Permitted Changes, and (c) incorporate any other Landlord-requested (and Tenant approved) Shell and Core Changes. As soon as such design development documents and the final construction documents
    (collectively, <b><i>&#8220;</i>Landlord&#8217;s Shell and Core Plans<i>&#8221;</i></b>) are completed, Landlord shall deliver the same to Tenant for Tenant&#8217;s approval, which approval may be withheld only if: (i) the applicable Landlord&#8217;s Shell and Core Work Plans are
    neither consistent with nor logical evolutions of the Approved Schematic Plans or the previously approved design development documents, as applicable, or (ii) such plans are otherwise inconsistent with the requirements of this paragraph<b>. </b>Such
    Landlord&#8217;s Shell and Core Plans shall be approved or disapproved by Tenant within ten (10) business days after delivery to Tenant (or five (5) business days with respect to any resubmission of plans to Tenant). If Tenant fails to respond within such
    ten (10) (or (five (5), as applicable) business day period, Landlord may provide a written reminder notice to Tenant. Tenant&#8217;s failure to respond to such reminder notice within five (5) business days after delivery of such notice shall be deemed
    approval by Tenant of the applicable Landlord&#8217;s Shell and Core Plans. If the applicable Landlord&#8217;s Shell and Core Plans are disapproved by Tenant, then Tenant shall notify Landlord in writing of its detailed objections to such Landlord&#8217;s Shell and Core
    Plans, and Landlord shall revise the applicable Landlord&#8217;s Shell and Core Plans accordingly unless it disputes the basis of such objections, in which case such dispute shall be resolved as provided in Section 13, below. The final Landlord&#8217;s Shell and
    Core Plans so approved, and all change orders and other changes thereto specifically permitted by this Work Letter, are referred to herein as the &#8220;<b>Approved Shell and Core Plans.</b>&#8221; If the Approved Schematic Plans are completed and finally approved
    by Landlord prior to the Effective Date, the parties acknowledge that they shall collaborate and cooperate to have Tenant cause the Architect to proceed with generating design development documents for the Landlord&#8217;s Construction Work, with the intent
    of completing the same for submission to the parties on or about December 9, 2022. The approval of the design development documents by Landlord, to the extent occurring prior to the Effective Date, shall be handled in the manner applicable to the
    schematic design documents. As a condition to the authorization of the architect to proceed with the design development phase prior to the Effective Date, the parties shall agree on how such sums shall be treated for the purposes of Construction Costs.
    The parties acknowledge and agree that the Approved Shell and Core Plans shall be designed to meet at least LEED Gold certification standards and Tenant shall, prior to the Effective Date, submit the Building for pre-certification under LEED Gold
    standards and diligently pursue pre-certification. The parties shall cooperate as reasonable required to obtain LEED Gold (or such better standard as has been designed) certification for the Building, Landlord and Tenant acknowledging that the
    inability to obtain such certification for matters not within the control of Landlord and Tenant (such as the failure of the LEED program to continue to exist) shall not be deemed to be a default hereunder.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The parties shall cooperate to schedule periodic design and construction meetings at mutually agreeable times, such meetings to take place no less
    often than monthly, with respect to Landlord&#8217;s Construction Work and Tenant Improvements, and (following commencement of the Tenant Improvements) bi-weekly with respect to the Tenant Improvements. The parties shall keep each other reasonably informed
    with respect to their respective work, and Landlord and Tenant agree to provide each other with such information as may be reasonably requested by the other party with respect to the Landlord&#8217;s Construction Work and Tenant Improvements, as applicable.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">5.3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Landlord Project Developer Fee</u>. Tenant shall be required to
    pay Landlord a (a) project developer fee in the amount of three (3%) percent of the hard and soft costs of construction of the Landlord&#8217;s Construction Work, and (b) an oversight fee in the amount of one (1%) percent of the hard and soft costs of
    construction of the Tenant Improvements (collectively, the &#8220;<b>Developer Fee</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">5.4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font><u>Changes to Shell and Core Plans</u>. Any changes to the Approved
    Shell and Core Plans (each, a &#8220;<b>Shell and Core Change</b>&#8221;) requested by Landlord or Tenant (other than Shell and Core Permitted Changes by Landlord, which do not require any approval) shall be requested and instituted in accordance with the
    provisions of this <u>Section 5.4</u> and shall be subject to the written approval of the other party in accordance with this Work Letter.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 36pt">(a)</td>
        <td style="text-align: justify"><u>Shell and Core Changes Requested by Tenant</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Shell and Core Tenant Change Order Request</u>. Following the
    Effective Date (but in no event later than the date that is one month following the date that the final Landlord&#8217;s Shell and Core Plans are submitted by Landlord to Tenant for approval), Tenant may request Shell and Core Changes to the Approved Shell
    and Core Plans to accommodate the design of the Tenant Improvements by notifying Landlord thereof in writing in a change order form provided by Landlord that is substantially the same form as the AIA standard change order form (a &#8220;<b>Shell and Core
      Tenant Change Order Request</b>&#8221;), which Shell and Core Tenant Change Order Request shall detail the nature and extent of any requested Shell and Core Changes, including, without limitation, (A) the Shell and Core Change and (B) any modification of
    the Approved Shell and Core Plans, as applicable. In the event Landlord approves any Shell and Core Change, Landlord shall: (1) notify Tenant if it reasonably believes such Shell and Core Change could cause a delay in the Estimated Delivery Condition
    Date or the Estimated Substantial Completion Date; and (2) provide Landlord&#8217;s reasonable estimate of any additional costs and expenses associated with such Shell and Core Change. Shell and Core Tenant Change Order Requests shall be signed by Tenant&#8217;s
    Authorized Representative.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Approval of Shell and Core Changes</u>. All Tenant-
    requested Shell and Core Changes shall be subject to Landlord&#8217;s prior written approval, which shall not be unreasonably withheld, conditioned or delayed so long as such Shell and Core Change, as reasonably determined by Landlord, (A) could not
    reasonably be expected to (1) adversely impact (a) the exterior appearance of the Building, (b) the structural aspects of the Building, or (c) any building system, including, without limitation, the HVAC, mechanical, electrical, plumbing or life safety
    systems installed in connection with the Landlord&#8217;s Construction Work; (2) create a foreseeable risk of violating any, or actually violate any, Applicable Law or the Permits and Approvals (or require a modification of the same), or any other permit
    requirement, (3) materially increase insurance premiums; (4) in Landlord&#8217;s reasonable judgment, materially reduce the quality or value of the Building or the Property, (5) result in a Fundamental Change, or (6) delay the occurrence of Delivery
    Condition or Substantial Completion of the Landlord&#8217;s Construction Work by more than 30 days when combined with all other then-existing Tenant Delays (each, a &#8220;<b>Design Problem</b>&#8221;), and (B) will not cause the hard costs of the Landlord&#8217;s
    Construction Work to increase by more than one (1%) percent in the aggregate (based on the Landlord&#8217;s Budget) unless Tenant makes provisions to pay for the same that are acceptable to Landlord and its construction lender. Landlord shall have ten (10)
    days after receipt of a Shell and Core Tenant Change Order Request to notify Tenant in writing of Landlord&#8217;s decision either to approve or disapprove Tenant- requested Shell and Core Change. If Landlord fails to respond within such ten (10) day period,
    Tenant may provide a written reminder notice to Landlord. Landlord&#8217;s failure to respond to such reminder notice within three (3) days after delivery of such notice shall be deemed approval by Landlord of the Shell and Core Tenant Change Order Request.
    Any dispute regarding the Landlord&#8217;s disapproval of a Shell and Core Tenant Change Order Request shall be resolved in accordance with Section 13, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in">(b)</td>
        <td style="text-align: justify"><u>Shell and Core Changes Requested by Landlord</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Shell and Core Landlord Change Order Request</u>. Landlord may
    request Shell and Core Changes to the Landlord&#8217;s Construction Work by notifying Tenant thereof in writing in a change order form provided by Landlord that is substantially the same form as the AIA standard change order form (a &#8220;<b>Shell and Core
      Landlord Change Order Request</b>&#8221;), which Shell and Core Landlord Change Order Request shall detail the nature and extent of any requested Shell and Core Changes, including, without limitation, (A) the Shell and Core Change, (B) any modification of
    the Design Development Plans or the Approved Shell and Core Plans, as applicable, and (C) any changes to the Estimated Delivery Condition Date or Estimated Substantial Completion Date resulting from the Shell and Core Change. Notwithstanding the
    foregoing or anything herein to the contrary, Landlord shall have no obligation to request the approval of Shell and Core Permitted Changes.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 1.5in; text-align: justify">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Tenant&#8217;s Approval of Shell and Core Change</u>. Tenant shall have ten (10) days after receipt of a Shell
    and Core Landlord Change Order Request to notify Landlord in writing of Tenant&#8217;s approval or rejection of the Landlord-requested Shell and Core Change, which approval shall not be unreasonably withheld, conditioned or delayed. If Tenant fails to
    respond within such ten (10) day period, then Landlord may provide Tenant with a second written notice stating that &#8220;Tenant&#8217;s failure to respond within three (3) days after Landlord&#8217;s second notice shall be deemed Tenant&#8217;s approval to such Shell and
    Core Landlord Change Order Request,&#8221; and if Tenant does not respond with such three (3) day period, then Tenant shall be deemed to have approved such Shell and Core Landlord Change Order Request. Any dispute regarding the Tenant&#8217;s disapproval of a
    Shell and Core Tenant Change Order Request shall be resolved in accordance with Section 13, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Shell and Core Permitted Changes</u>. For purposes of this Work
    Letter, a &#8220;<b>Shell and Core Permitted Change</b>&#8221; shall mean: (i) minor field changes; (ii) changes required by governmental authority or to comply with Permits and Approvals or Applicable Laws; (iii) any other changes that both: (A) could not
    reasonably be expected to (1) adversely impact (a) the structural aspects of the Building, (b) the exterior appearance of the Building (other than de minimis changes that do not result from a change in exterior material specifications, such as
    locations of items behind screening on the roof, final adjustments in the positioning of exterior doors or loading bays, and the like), (c) Tenant&#8217;s ability to construct the Tenant Improvements as shown on the Approved TI Plans, or (d) any building
    system, including, without limitation, the HVAC, mechanical, electrical, plumbing or life safety systems installed in connection with the Landlord&#8217;s Construction Work; (2) create a foreseeable risk of violating any, or actually violate any, Applicable
    Law or the Permits and Approvals (or require a modification of the same), or any other permit requirement, (3) materially increase insurance premiums; or (4) delay the Substantial Completion of the Landlord&#8217;s Construction Work by more than 30 days, and
    (B) do not materially change the size, cost, configuration, or overall appearance of the Building, Bridge or Parking Structure, materially and adversely affect Landlord&#8217;s ability to perform the Landlord&#8217;s Construction Work or materially and adversely
    affect Tenant&#8217;s ability to operate its business in the Building, and (iv) changes required for the ordinary development of the Approved Shell and Core Plans in a manner not inconsistent with the Approved Shell and Core Plans. Shell and Core Permitted
    Changes may be made by Landlord in its reasonable discretion.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">6.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant Improvements</u>. Following delivery of the Premises to
    Tenant on the Delivery Date, the Tenant Improvements shall be performed by Tenant at Tenant&#8217;s sole cost and expense (subject to the TI Allowance) substantially in accordance with the Approved TI Plans (subject only to changes made in accordance with <u>Section






      6.3), </u>the provisions of the Lease governing Alterations (to the extent not inconsistent with this Work Letter), and this Work Letter. The schedule for the construction of the Tenant Improvements shall be in accordance with a schedule to be
    prepared by Tenant&#8217;s general contractor (the &#8220;<b>TI Schedule</b>&#8221;). Tenant shall prepare the TI Schedule so that it is a reasonable schedule for the completion of the Tenant Improvements, taking into account the work necessary for Landlord to achieve
    Substantial Completion by the date set forth in the GMP Contract. The TI Schedule shall clearly identify estimated dates and time periods when Tenant&#8217;s contractor will require access to areas that are under construction by Landlord. As soon as the TI
    Schedule is completed, Tenant shall deliver the same to Landlord for Landlord&#8217;s approval, which approval shall not be unreasonably withheld, conditioned or delayed. Such TI Schedule shall be approved or disapproved by Landlord, following consultation
    with Landlord&#8217;s General Contractor, within ten (10) business days after delivery to Landlord. Landlord&#8217;s failure to respond within such ten (10) business day period shall be deemed approval by Landlord. If Landlord disapproves the TI Schedule, then
    Landlord shall notify Tenant in writing of its objections to such TI Schedule, with reasonable detail, and the parties shall confer and negotiate in good faith to reach agreement on the TI Schedule.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">6.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>TI Plans</u>. Tenant shall retain an architect reasonably
    approved by Landlord (the &#8220;<b>TI Architect</b>&#8221;) to design the tenant improvements necessary for Tenant&#8217;s particular use and occupancy of the Premises in accordance with the program attached as <u>Schedule 5</u> and items identified as &#8220;by Tenant&#8221; on
    the allocation of responsibility attached as <u>Schedule 2</u>. Landlord acknowledges that it has approved the use of DGA as the TI Architect. Tenant shall cause the TI Architect to prepare, and Landlord shall approve, schematic plans, design
    development plans, and 100% construction document plans (the &#8220;<b>TI Plans</b>&#8221;), in each case fully coordinated with the Approved Core and Shell Plans, all in accordance with the milestone dates set forth on <u>Schedule 4</u>, subject to Force Majeure
    and Landlord Delays (as defined below). The TI Plans shall provide for a minimum investment equal to the TI Allowance across the entire Premises in accordance with the Approved Budget (as defined below). All material and equipment furnished by Tenant
    or its contractors as the Tenant Improvements shall be new or &#8220;like new;&#8221; and the quality of the Tenant Improvements shall be of a nature and character not less than a first-class standard for life sciences facilities. Any engineers used by Tenant or
    Tenant&#8217;s TI Architect in the design of the Tenant Improvements shall be subject to Landlord&#8217;s reasonable consent, Landlord acknowledging that the engineers referenced in Section 4.2 above, are deemed approved. Even if any such architect or engineers
    may have been otherwise engaged by Landlord or Landlord&#8217;s affiliates in connection with the Landlord&#8217;s Construction Work or any other property, Tenant shall be solely responsible for the liabilities and expenses of all architectural and engineering
    services relating to the Tenant Improvements (subject to reimbursement from the TI Allowance as provided below) and for the adequacy and completeness of the TI Plans submitted to Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#8220;<b>Landlord Delays</b>&#8221; means any actual delay in the design of the Tenant Improvements to the extent resulting from the acts or omissions of
    Landlord or any Landlord Party, including, without limitation, any Landlord-requested TI Change. Except for Landlord Delays due to any Landlord requested TI Change for which Tenant provided to Landlord the estimated amount of any associated Landlord
    Delay (for which no notice will be required, and no obligation of Tenant to grant such request other than as expressly provided herein), if there is an event that Tenant contends is a Landlord Delay, then Tenant shall give Landlord written notice of
    such Tenant Delay as soon as is practicable following Tenant&#8217;s knowledge of such delay (&#8220;<b>TI Delay Notice</b>&#8221;) (provided, however, that no Landlord Delay shall be deemed to accrue under this Work Letter with respect to the Landlord Delay referenced
    in a TI Delay Notice until Tenant provides Landlord with such TI Delay Notice).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Any Landlord Delay of less than a full day shall be deemed to be equal to a delay of one&#160;(1) full day. Landlord and Tenant have agreed to
    determine the length of any Landlord Delay as follows: (i) any delays resulting from the failure of Landlord to act within a time period specified in this Work Letter with respect to the approval of the TI Plans shall be equal to one (1) day for each
    day that the applicable Landlord Delay continues beyond the applicable time period required for such action under the Lease, (ii) in the event of any agreed Landlord Delay, as the parties may agree in writing from time to time, the length of such
    Landlord Delay shall be as agreed upon in writing by the parties at the time such Landlord Delay arises, and (iii) with respect to any other Landlord Delay, Tenant shall notify Landlord in writing of the claimed estimated length of such Landlord Delay
    within ten (10) business days after its occurrence and Landlord may elect by written notice delivered to the other within ten (10) business days thereafter to dispute the claimed estimated Landlord Delay in accordance with <u>Section 13</u> of this
    Work Letter. Unless such estimate is disputed by written notice delivered within such ten (10) business day period, the length of such Landlord Delay shall be no less than the claimed estimated Landlord Delay.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">6.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Approved TI Plans</u>. Tenant shall prepare TI Plans that: (a)
    are consistent with and are logical evolutions of the previously approved iteration of the TI Plans, (b) incorporate any TI Permitted Changes, and (c) incorporate any other Landlord-requested (and Tenant approved) TI Changes. As soon as an applicable
    phase (i.e. schematic development, design development, and construction drawings) of TI Plans are completed, Tenant shall deliver the same to Landlord for Landlord&#8217;s approval, which approval shall not be unreasonably withheld, conditioned, or delayed
    so long as such TI Plans are consistent with the previously approved TI Plans and do not cause Design Problems. Such TI Plans shall be approved or disapproved by Landlord within ten (10) business days after delivery to Landlord. If Landlord fails to
    notify Tenant of disapproval within such ten (10) business day period, then Tenant may provide Landlord with a second written notice stating that &#8220;Landlord&#8217;s failure to respond within five (5) business days after Tenant&#8217;s second notice shall be deemed
    Landlord&#8217;s approval to such TI Plans,&#8221; and if Landlord does not respond within such five (5) business day period, then Landlord shall be deemed to have approved such TI Plans. If the TI Plans are disapproved by Landlord, Landlord shall notify Tenant in
    writing of its objections to such TI Plans. Any dispute regarding Landlord&#8217;s disapproval of TI Plans shall be resolved in accordance with Section 13, below. After the 100% final construction document phase of TI Plans are approved by Landlord and
    Tenant, Tenant shall promptly submit such TI Plans to each appropriate governmental authority for approval. The TI Plans so approved, and all change orders and other changes thereto specifically permitted by this Work Letter, are referred to herein as
    the &#8220;<b>Approved TI Plans</b>&#8221;.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">6.3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Changes to Tenant Improvements</u>. Any changes to the TI
    Plans or the Approved TI Plans (each, a &#8220;<b>TI Change</b>&#8221;) requested by Landlord or Tenant (other than TI Permitted Changes by Landlord which do not require any approval) shall be requested and instituted in accordance with the provisions of this <u>Section






      6.3</u> and shall be subject to the written approval of the other party in accordance with this Work Letter.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in">(a)</td>
        <td style="text-align: justify"><u>TI Changes Requested by Tenant</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>TI Tenant Change Order Request</u>. Tenant may request TI
    Changes after Landlord approves the approved design development phase of the TI Plans or the Approved TI Plans by notifying Landlord thereof in writing in a change order form provided by Landlord that is substantially the same form as the AIA standard
    change order form (a &#8220;<b>TI Tenant Change Order Request</b><i>&#8221;<b>), </b></i>which TI Tenant Change Order Request shall detail the nature and extent of any requested TI Changes, including, without limitation, (A) the TI Change and (B) any modification
    of the TI Plans or Approved TI Plans, as applicable.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Landlord&#8217;s Approval of TI Changes</u>. All Tenant-requested TI
    Changes shall be subject to Landlord&#8217;s prior written approval, which shall not be unreasonably withheld, conditioned or delayed, provided that (a) such changes are not Fundamental Changes, (b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;
    </font>such changes do not require any modification of the Permits and Approvals for the Landlord&#8217;s Construction Work, (c) such changes do not require any modification of the Landlord&#8217;s Construction Work, (d) the requested work is compatible with the
    design, quality, equipment or systems of the Landlord&#8217;s Construction Work, or (e) such changes otherwise comply with the provisions of the Lease. Landlord shall have ten (10) business days after receipt of a TI Tenant Change Order Request to notify
    Tenant in writing of Landlord&#8217;s decision either to approve or disapprove the Tenant- requested TI Change. If Landlord does not approve in writing a Tenant requested TI Change within ten (10) business days after receipt of a TI Tenant Change Order
    Request, Tenant may provide a written reminder notice to Landlord. Landlord&#8217;s failure to respond to such reminder notice within five (5) business days after delivery of such notice shall be deemed a rejection of such request by Landlord, and the Tenant
    Improvements shall not be altered as contemplated by such TI Tenant Change Order Request. Any dispute regarding the Landlord&#8217;s disapproval of a TI Tenant Change Order Request shall be resolved in accordance with Section 13, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in">(b)</td>
        <td style="text-align: justify"><u>TI Changes Requested by Landlord</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>TI Landlord Change Order Request</u>. Landlord may request TI
    Changes by notifying Tenant thereof in writing in a change order form provided by Landlord that is substantially the same form as the AIA standard change order form (a &#8220;<b>TI Landlord Change Order Request</b>&#8221;), which TI Landlord Change Order Request
    shall detail the nature and extent of any requested TI Changes, including, without limitation, (A) the TI Change, and (B) any modification of the TI Plans or the Approved TI Plans, as applicable. Notwithstanding the foregoing to the contrary, Tenant&#8217;s
    approval is not required for TI Permitted Changes, as defined below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant&#8217;s Approval of TI Change</u>. Tenant shall have ten (10)
    days after receipt of a TI Landlord Change Order Request to notify Landlord in writing of Tenant&#8217;s approval or rejection of the Landlord-requested TI Change, which approval shall not be unreasonably withheld, conditioned or delayed, so long as such TI
    Landlord Change Order Request, as reasonably determined by Tenant, (A) could not reasonably be expected to (1) adversely impact the functionality or, in more than a de minimis manner, the appearance of the Tenant Improvements; (2) create a foreseeable
    risk of violating any, or actually violate any, Applicable Law or the Permits and Approvals (or require a modification of the same), or any other permit requirement, (3) materially increase insurance premiums; (4) result in a Fundamental Change, or (5)
    delay the completion of the Tenant Improvements in more than a de minimis manner (each, a &#8220;<b>TI Design Problem</b>&#8221;), and (B) following the final approval of the Approved TI Plans, will not cause the hard costs of the Tenant Improvements to increase
    by more than one (1%) percent in the aggregate (unless Landlord agrees to pay the same, in which case such amount shall be included in Construction Costs as a soft cost). If Tenant fails to respond within such ten (10) days period, then Landlord may
    provide Tenant with a second written notice stating &#8220;that Tenant&#8217;s failure to respond within three (3) days after Landlord&#8217;s second notice shall be deemed Tenant&#8217;s approval to such Landlord-requested TI Change,&#8221; and if Tenant does not respond within
    such three (3) day period, then Tenant shall be deemed to have approved such Landlord-requested TI Change.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>TI Permitted Changes</u>. For purposes of this Work Letter, a &#8220;<b>TI






      Permitted Change</b>&#8221; shall mean (i) minor field changes; (ii) changes required by governmental authority or to comply with Applicable Laws; and (iii) changes that, when viewed in the aggregate, constitute Minor Alterations, as defined in the Lease.
    TI Permitted Changes may be made by Tenant in its sole but reasonable discretion. Tenant shall provide Landlord with reasonable prior notice of any TI Permitted Changes (other than minor field changes, of which Tenant shall provide notice as soon as
    reasonably practicable).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in"> 6.4. <u>Construction of the Tenant Improvements; Coordination</u>.</p>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;</font>Tenant shall retain the Landlord&#8217;s General Contractor to construct the Tenant
    Improvements and shall obtain Landlord&#8217;s prior written approval of the construction contract for the Tenant Improvements, which approval shall not be unreasonably withheld, conditioned, or delayed. Following approval of the Approved TI Plans, Tenant
    shall obtain all governmental approvals, authorizations, licenses, and permits (collectively, the &#8220;<b>Approvals</b>&#8221;) necessary for the construction of the Tenant Improvements and provide copies of the same to Landlord. Tenant shall provide Landlord
    with a copy of the application for any material Approvals prior to submitting the same. The Approvals shall not contain material conditions that survive the termination of the Lease without the prior written consent of Landlord, such consent not to be
    unreasonably withheld, conditioned or delayed. Landlord shall cooperate with Tenant to obtain the Approvals, at no out of pocket cost or liability to Landlord. Following receipt of the Approvals, Tenant shall promptly commence and diligently prosecute
    to completion the Tenant Improvements in accordance with, and subject to, the provisions of this Work Letter and Section 3.4 of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">All Tenant Improvements shall be performed and constructed by Tenant in accordance with the Approved TI Plans and in compliance with Applicable
    Laws and the Approvals. No Tenant Improvements shall be performed except in accordance with the Approved TI Plans, as they may be modified in accordance with this Work Letter. Prior to the commencement of the Tenant Improvements, Tenant shall deliver
    to Landlord a copy of any contract with Tenant&#8217;s contractors (including the architect), and certificates of insurance from the architect and any contractor performing any part of the Tenant Improvements evidencing insurance in compliance with the terms
    of the Lease. Tenant shall endeavor to have Landlord named as a third-party beneficiary (on a non-exclusive basis) of any contract entered into by Tenant with the Tenant&#8217;s architect, any consultant providing design or engineering services for the
    Tenant Improvements, any contractor or any subcontractor, and of any warranty or indemnity made by any contractor or any subcontractor. Landlord shall not exercise its rights with respect to its third party beneficiary status under the immediately
    preceding sentence unless (i) Tenant is in default under the Lease beyond applicable notice and cure periods, (ii) the Lease has otherwise terminated or otherwise is no longer in effect, or (iii) otherwise where Landlord has a bona fide, good faith
    claim against such architect, consultant, contractor, or subcontractor, in which case Landlord and Tenant will cooperate to pursue such claim. All Tenant Improvements shall be constructed in a good and workmanlike manner, in compliance with Applicable
    Laws. All Tenant contracts related to the Tenant Improvements shall provide that Tenant may assign such contracts and any warranties with respect to the Tenant Improvements to Landlord, upon Landlord&#8217;s request, effective at the end of the Term or in
    the event of a Default by Tenant under the Lease. Tenant shall take, and shall require its contractors to take, commercially reasonable steps to protect the Premises from damage as a result of the performance of any Tenant Improvements, including
    covering or temporarily removing any window coverings so as to guard against dust, debris or damage. Tenant shall conduct the Tenant Improvements in a manner that reasonably minimizes interference with other construction activities at the Premises, in
    a manner consistent with first-class life sciences buildings.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Tenant shall diligently prosecute and substantially complete the Tenant Improvements on or before the first anniversary of the Commencement Date.
    For purposes of this paragraph, &#8220;substantially complete&#8221; and &#8220;substantial completion&#8221; shall mean that the Tenant Improvements have been completed, other than minor punchlist-type items the completion of which will not unreasonably delay or interfere
    use of the affected areas of the Premises for the regular conduct of business. Promptly following substantial completion, Tenant shall provide Landlord with a certificate of substantial completion by Tenant&#8217;s architect on a form reasonably approved by
    Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160; </font>Landlord and Tenant shall reasonably cooperate so as to coordinate the
    management, administration, and schedule of the Landlord&#8217;s Construction Work and the Tenant Improvements following the Delivery Date in a manner that will permit Landlord to achieve its obligations to lenders and Tenant, and permit Landlord to achieve
    Substantial Completion by the Estimated Substantial Completion Date, and permit Tenant to complete the Tenant Improvements in a reasonably expeditious manner.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">7.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Force Majeure</u>. Any prevention, delay or stoppage due to
    strikes, lockouts, labor disputes, acts of God, acts of war, terrorist acts, inability to obtain, or delays in obtaining, services, labor, or materials or reasonable substitutes therefor (including without limitation supply chain delays), governmental
    actions, civil commotions, casualty, actual or threatened public health emergency (including, without limitation, epidemic, pandemic, famine, disease, plague, quarantine, and other significant public health risk, such as the epidemic known as COVID-19
    and its variants), governmental edicts, actions, declarations or quarantines by a governmental entity or health organization (including, without limitation, any shelter-in-place orders, stay at home orders or any restrictions on travel related thereto
    that preclude Tenant, its agents, contractors or its employees from accessing the Project for the activities related to construction of the Improvements, national or regional emergency), breaches in cybersecurity, and other causes beyond the reasonable
    control of the party obligated to perform, regardless of whether such other causes are (i) foreseeable or unforeseeable or (ii) related to the specifically enumerated events in this paragraph (collectively, a &#8220;<b>Force Majeure</b>&#8221;), shall excuse the
    performance of such party for a period equal to any such prevention, delay or stoppage and, therefore, if this Work Letter specifies a time period for performance of an obligation of either party, that time period shall be extended by the period of any
    delay in such party&#8217;s performance caused by a Force Majeure. For purposes of this Section 5, the following shall be included as causes beyond the reasonable control of the party obligated to perform: epidemic; pandemic; disease; illness; national,
    regional or local emergency; quarantine; and governmental order. Notwithstanding anything to the contrary in this Work Letter, the inability to obtain financing or investment, or a lack of funding, shall not excuse a party&#8217;s performance of its
    obligations hereunder.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Insurance</u>.</p>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">8.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Property Insurance</u>. At all times during the period beginning
    with commencement of construction of the Landlord&#8217;s Construction Work and ending when the Landlord&#8217;s Construction Work is Complete pursuant to <u>Section 11</u> of this Work Letter, Landlord shall maintain or cause to be maintained (in addition to the
    insurance required pursuant to the Lease) property insurance insuring Landlord and its affiliates, agents and employees, as their interests may appear. Such policy shall, on a completed values basis for the full insurable value at all times, insure
    against loss or damage by fire, vandalism and malicious mischief and other such risks as are customarily covered by the so-called &#8220;broad form extended coverage endorsement&#8221; upon all Landlord&#8217;s Construction Work and the General Contractor&#8217;s and any
    subcontractors&#8217; machinery, tools and equipment, all while each forms a part of, or is contained in, the Landlord&#8217;s Construction Work or any temporary structures on the Premises, or is adjacent thereto; provided that, for the avoidance of doubt,
    insurance coverage with respect to the General Contractor&#8217;s and any subcontractors&#8217; machinery, tools and equipment shall be carried on a primary basis by such General Contractor or subcontractor. Landlord agrees to pay any deductible, which deductible
    amount shall be considered a Construction Cost. Said property insurance shall contain an express waiver of any right of subrogation by the insurer against Tenant and its affiliates, agents and employees.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">8.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Workers&#8217; Compensation Insurance</u>. At all times during the
    period of construction of the Landlord&#8217;s Construction Work, Landlord shall, and shall cause its contractors or subcontractors to, maintain statutory workers&#8217; compensation insurance as required by Applicable Laws.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">8.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Tenant&#8217;s Insurance</u>. At all times during the period of construction of the Tenant Improvements, Tenant shall, and shall its
    contractors and subcontractors to, maintain insurance as required pursuant to the Tenant Construction Manual referenced in the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">9.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Requests for Consent</u>. Except as otherwise provided in this Work
    Letter, Tenant shall respond to all requests for consents, approvals, information, or directions made by Landlord pursuant to this Work Letter within five (5) days following Tenant&#8217;s receipt of such request. If Tenant fails to respond within such five
    (5) days period, then Landlord may provide Tenant with a second written notice stating that &#8220;Tenant&#8217;s failure to respond within two (2) days after Landlord&#8217;s second notice shall be deemed approval by Tenant,&#8221; and if Tenant does not respond within such
    two (2) day period, then Tenant shall be deemed to have approved such item.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Budget and Tenant Improvement Allowance</u>.</p>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">10.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Budget</u>. A preliminary budget for all hard and soft costs
    pertaining to the Landlord&#8217;s Construction Work is attached hereto as <u>Schedule 6</u> to the Work Letter (as the same may be modified or otherwise updated in accordance with this Work Letter, the &#8220;<b>Budget&#8221;</b>). The Budget includes a line item for
    contingency. Landlord may reallocate line items within the Budget and use the contingency in its sole discretion at any time. Landlord will use commercially reasonable efforts to provide Tenant with updates to the Budget and shall revise the Budget to
    reflect the final GMP; <i>provided</i> at a minimum, following the final approval of the Approved Core and Shell Plans Landlord shall provide Tenant with a monthly updated Budget and a reconciliation of actual costs incurred through the prior month.
    In addition, Landlord will (or will request that the General Contractor) copy Ionis Chief Accounting Officer, Dennis Gonzales (e-mail address: [***]) on all draw packages submitted to Landlord by the General Contractor related to the Landlord&#8217;s
    Construction Work. The Budget is for informational purposes only and is not binding on Landlord in any respect, and shall not create any limit on Aggregate Disbursements.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">10.2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Tenant Improvement Allowance</u>. Provided no monetary or
    material non-monetary Event of Default exists, Landlord shall provide Tenant with a Tenant Improvement allowance (&#8220;<b>TI Allowance</b>&#8221;) of $41,208,250.00, which TI Allowance shall automatically be reduced by the amount of $15 per gross square foot
    (based on the agreed-upon 164,833 gross square feet set forth in the Lease) for every whole 1% reduction in the ratio of lab to office below 40% as finally determined in the Approved TI Plans by the Architect (or as affected by any subsequent TI
    Change), nothing in this sentence being deemed to modify the Fundamental Requirements, which require the lab-to-office ratio to be no less than 35% to 65%. The TI Allowance can be applied by Tenant to offset the cost to permit, design and construct the
    Tenant Improvements (provided that in no event shall the TI Allowance be applied towards design and other so-called &#8220;soft costs&#8221;, including without limitation consultant fees and the costs to acquire and install furniture, fixtures, and equipment) in
    an amount that exceeds 10% of the TI Allowance. Except as set forth in the immediately preceding sentence, in no event shall any of the TI Allowance be used for the acquisition of Tenant&#8217;s furniture, fixtures, or equipment or other items of personal
    property, such as cabling and wiring. In no event may the TI Allowance be used for payments to any affiliates of Tenant. Landlord shall have no obligation to make any disbursements of TI Allowance not properly requisitioned by Tenant by the date that
    is one year following the Commencement Date and Tenant shall have no further right to any undisbursed TI Allowance thereafter.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(i)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The TI Allowance will be available for monthly disbursements for
    permitted soft costs from and after the Effective Date of the Lease and for permitted hard costs following the commencement of the Tenant Improvements subject to the requirements set forth in this Work Letter. Landlord shall pay Landlord&#8217;s Proportion
    (as defined below) of invoices made by Tenant on a form provided by Landlord within forty-five (45) days of receipt of a complete submission from Tenant (as set forth below), if Tenant requests and Landlord has received a satisfactory confirmation of
    non-responsibility on a form provided by Landlord, directly to the applicable vendor as requested by Tenant or to Tenant (to the extent Tenant has paid such requisitioned costs) on a progress payment basis. As a condition to Landlord&#8217;s disbursement of
    any portion of the TI Allowance, Tenant shall provide Landlord with (A) appropriate paid or unpaid receipts or invoices for the amount requested to be paid from the TI Allowance, (B) partial, conditional lien waivers for such work from all persons or
    entities that could file mechanics&#8217; or materialmen&#8217;s liens against the Building or the Project with respect to all work performed or services or materials provided through the date of each such invoice (subject only to receipt of the requisitioned
    amount) and, as a condition to the final release of retainage, final unconditional lien waivers for final payments, as applicable, for any contracts greater than Twenty Five Thousand Dollars ($25,000.00), which lien waivers shall comply with the
    appropriate provisions of California Civil Code, as reasonably determined by Landlord, (C) written authorization from Tenant to disburse the portion of the TI Allowance being requisitioned on a reasonable form provided by Landlord, (D) an application
    for payment from the Tenant&#8217;s general contractors as approved and executed by Tenant and Tenant&#8217;s architect, (E) evidence that amounts previously requisitioned by Tenant from the TI Allowance have been paid in full to the applicable third parties, and
    (F) such other documentation as may be reasonably requested by Landlord or its lender<b><i>. </i></b>Tenant may not make a requisition for application of the TI Allowance more frequently than once a month. The final disbursement of the TI Allowance
    shall be conditioned upon the recording of a Notice of Completion in a form reasonably approved by Landlord in the applicable county office.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 39pt">&#8220;<b>Landlord&#8217;s Proportion</b>&#8221; shall be a fraction, the numerator of which is the TI Allowance and the denominator of which is the sum of (1) the
    total contract price for the design and engineering of the Tenant Improvements and (2) the total contract price for the construction of the Tenant Improvements (as evidenced by reasonably detailed documentation delivered to Landlord upon Landlord&#8217;s
    request). Notwithstanding anything to the contrary set forth elsewhere in this Work Letter, Landlord shall not have any obligation to expend any portion of the TI Allowance until Landlord has approved in writing the budget for the Tenant Improvements
    (the &#8220;<b>Approved Budget</b>&#8221;), such approval not to be unreasonably withheld, conditioned, or delayed. The proposed Approved Budget shall be approved or disapproved by Landlord within ten (10) business days after delivery to Landlord. If Landlord
    fails to notify Tenant of disapproval within such ten (10) business day period, then Tenant may provide Landlord with a second written notice stating that &#8220;Landlord&#8217;s failure to respond within five (5) business days after Tenant&#8217;s second notice shall
    be deemed Landlord&#8217;s approval to such Approved Budget,&#8221; and if Landlord does not respond within such five (5) business day period, then Landlord shall be deemed to have approved Tenant&#8217;s proposed Approved Budget. Prior to Landlord&#8217;s approval of the
    Approved Budget, Tenant shall pay all of the costs and expenses incurred in connection with the Tenant Improvements as they become due, subject to reimbursement from the Tenant Improvement Allowance following Landlord&#8217;s approval of the Approved Budget.
    The Approved Budget shall provide for approximately proportionate spending across the entire Premises on a per square foot basis (subject to customary and/or reasonable variations on a floor-by-floor basis for the applicable use mix on such floor, such
    as between office and laboratory space). Landlord shall not be obligated to reimburse Tenant for costs or expenses relating to the Tenant Improvements that exceed the amount of the TI Allowance.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 39pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">(ii)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>In the event Landlord fails to fund any portion of the Allowance
    when properly due hereunder within the aforementioned forty-five (45) day period, Tenant shall deliver written notice to Landlord and its lender stating that &#8220;Failure to fund the amount set forth in this request within 30 days may result in Tenant
    offset rights&#8221;. If Landlord fails to remit such payment within an additional thirty (30) days following Landlord&#8217;s receipt of Tenant&#8217;s notice, Tenant shall have the right to offset such amounts against the next installments of Monthly Rent that become
    due and owing, which unpaid amounts shall bear interest at the Interest Rate accruing from the date the same were due and payable through the date paid in. Notwithstanding the foregoing, no such offset shall arise or accrue if Landlord disputes the
    Tenant&#8217;s claim to an offset within ten (10) business days following Tenant&#8217;s notice of the same. Any such disputes shall be resolved in accordance with Section 13, below.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">11.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Completion of Improvements</u>. The Landlord&#8217;s Construction Work
    shall be deemed &#8220;<b>Complete</b>&#8221; at such time as (a) Substantial Completion has occurred, (b) Landlord shall have provided Tenant with evidence that (i) the Landlord&#8217;s Construction Work has been completed and paid for in full (which shall be evidenced
    by the Architect&#8217;s certificate of completion), other than as provided in clause (ii), below, and (ii) the Punchlist Items (including any deficiencies noted in a third-party commissioning report for the Landlord&#8217;s Construction Work, to the extent the
    same is included within the scope of the GMP Contract) have been completed and paid for in full, other than seasonal work such as landscaping. Following Completion, Landlord shall provide Tenant with electronic CADD files of the Landlord&#8217;s Construction
    Work.</p>
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  </div>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">12.</td>
        <td style="text-align: justify"><u>Tenant Delays</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#8220;<b>Tenant Delay</b>&#8221; means any actual delay in the Landlord&#8217;s
    Construction Work to the extent resulting from the acts or omissions of Tenant or any Tenant Party (rather than from Force Majeure or other delays that may have occurred due to Landlord&#8217;s General Contractor, for example), including, without limitation,
    due to any accommodation of a Tenant initiated request (e.g., a Tenant requested change to the Schedule), any Tenant requested Shell and Core Change, interference with the Substantial Completion of the Landlord&#8217;s Work (including without limitation on
    account of Tenant&#8217;s early access pursuant to Section 3.4, above), or failure of Tenant to provide its specifications for the Building Management System by the date required on <u>Schedule 3</u>. Except for Tenant Delays due to accommodation of a
    Tenant initiated request or any Tenant requested Shell and Core Change for which Landlord provided to Tenant the estimated amount of any associated Tenant Delay (for which no notice will be required, and no obligation of Landlord to grant such request
    other than as expressly provided herein) or delays resulting from Tenant&#8217;s failure to respond to act within the periods set forth in this Work Letter, if there is an event that Landlord contends is a Tenant Delay, then Landlord shall give Tenant
    written notice of such Tenant Delay as soon as is practicable following Landlord&#8217;s knowledge of such delay (&#8220;<b>LW Delay Notice</b>&#8221;) (provided, however, that no Tenant Delay shall be deemed to accrue under this Work Letter with respect to the Tenant
    Delay referenced in a LW Delay Notice until Landlord provides Tenant with such LW Delay Notice).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Any Tenant Delay of less than a full day shall be deemed to be
    equal to a delay of one (1) full day. Landlord and Tenant have agreed to determine the length of any Tenant Delay as follows: (i) any delays resulting from the failure of Tenant to act within a time period specified in this Work Letter shall be equal
    to one (1) day for each day that the applicable Tenant Delay continues beyond the applicable time period required for such action under the Lease, (ii) in the event of any agreed Tenant Delay, as the parties may agree in writing from time to time, the
    length of such Tenant Delay shall be as agreed upon in writing by the parties at the time such Tenant Delay arises, and (iii) with respect to any other Tenant Delay, Landlord shall notify Tenant in writing of the claimed estimated length of such Tenant
    Delay within ten (10) business days after its occurrence and Tenant may elect by written notice delivered to the other within ten (10) business days thereafter to dispute the claimed estimated Tenant Delay in accordance with <u>Section 13</u> of this
    Work Letter. Unless such estimate is disputed by written notice delivered within such ten (10) business day period, the length of such Tenant Delay shall be no less than the claimed estimated Tenant Delay.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; If the Landlord&#8217;s Construction Work is delayed by Tenant Delay, then the date on which the Landlord&#8217;s Construction Work would have
    achieved Delivery Condition or been Substantially Complete but for such Tenant Delay (i.e., without regard for Force Majeure or other delays that may have occurred but do not constitute Tenant Delays), as evidenced by written notice from Landlord to
    Tenant, shall be deemed to be the Delivery Date or the date of Substantially Completion, as applicable, unless such notice disputed in a written notice by Tenant to Landlord within five (5) business days after delivery of such determination, in which
    case such dispute will be determined by arbitration pursuant to 13, below.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in"><font style="font-weight: normal">13.</font></td>
        <td style="text-align: justify"><u>Dispute Resolution Process</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">13.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160; </font>All disputes between Landlord and Tenant regarding Tenant Delays and
    other matters expressly referencing this <u>Section 13</u> shall be resolved in accordance with this <u>Section 13</u>. Any arbitration decision under this <u>Section 13</u> shall be enforceable in accordance with Applicable Laws in any court of
    proper jurisdiction.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Any arbitration conducted pursuant to this <u>Section 13</u> shall
    be conducted in as expeditious manner as possible to avoid delays in the construction of Landlord&#8217;s Construction Work and Tenant Improvements.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Any and all claims or disputes to be resolved pursuant to this <u>Section






      13</u> shall be resolved as follows: Landlord and Tenant shall promptly meet and confer to attempt in good faith to resolve such dispute and, if such dispute is not fully resolved within fifteen (15) days after delivery of written notice of such
    dispute, the parties agree that the claims or disputes shall be settled by arbitration administered by the American Arbitration Association (&#8220;<b>AAA</b>&#8221;) under its Construction Industry Arbitration Rules (or any successor organization), and judgment
    on the award rendered by the arbitrator may be entered in any court having jurisdiction thereof. Further, Landlord and Tenant agree to direct the San Diego Regional Office of the AAA to appoint a single arbitrator who (i) shall have a minimum of
    fifteen (15) years of experience in construction disputes involving first class office and laboratory buildings in the appliable market, (ii) has not worked for either party for the prior five (5) years, (iii) is not be affiliated with either Landlord
    or Tenant, and (iv) has not worked for either party or its affiliates at any time during the prior five (5) years (a &#8220;<b>Qualified Construction Arbitrator</b>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">13.2 &#160;&#160;&#160;&#160;&#160;&#160;Both Landlord and Tenant shall have the opportunity to present evidence and outside consultants to the appointed arbitrator. The
    arbitrator shall decide the dispute by written decision. The arbitration shall be conducted in accordance with the expedited procedures of the AAA&#8217;s Construction Industry Arbitration Rules insofar as such rules are not inconsistent with the provisions
    of the Lease (in which case the provisions of the Lease shall govern) and shall be concluded, with a decision issued, no later than ten (10) business days after the date that such dispute is submitted to the appointed arbitrator. The decision of the
    arbitrator shall be final and binding on the parties. The parties shall comply with any orders of the arbitrator establishing deadlines for any such proceeding. The fee of the arbitrator shall be paid equally by the parties, and each party shall pay
    all other costs incurred by it in connection with the arbitration.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">14.</td>
        <td style="text-align: justify"><u>Miscellaneous</u>.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">14.1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Number; Headings</u>. Where applicable in this Work Letter, the
    singular includes the plural and the masculine or neuter includes the masculine, feminine and neuter. The section headings of this Work Letter are not a part of this Work Letter and shall have no effect upon the construction or interpretation of any
    part hereof.</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">80</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 1</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">PERMITS AND APPROVALS</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><u>Entitlements:</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Architectural Committee Review under the CCRs</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">CEQA determination that the project is exempt from CEQA<br>
    Site Development Plan</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><u>Ministerial Approvals</u>:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Grading Permit</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Lot Line Adjustment between Lots 21 &amp; 22 <br>
    Building Permit for Landlord&#8217;s Construction Work<br>
    Shoring Permit</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Landscaping Permit</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Traffic Control Permit for Pedestrian Bridge</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <!-- Field: Page; Sequence: 26 -->
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          <td style="text-align: center; width: 100%">&#160;</td>
        </tr>

    </table>
  </div>
  <div style="text-align: center;"><font style="font-family: 'Times New Roman',Times,serif; font-size: 8pt; color: rgb(0, 0, 0); font-weight: normal; font-style: normal;">81</font>
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    <table cellspacing="0" cellpadding="0" style="width: 100%">

        <tr>
          <td style="text-align: center; width: 100%">&#160;</td>
        </tr>

    </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 2</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">CONCEPT PLAN AND ALLOCATION OF RESPONSIBILITY</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Site Development Permit Package SDP 2021-0029 Prepared by DGA and last revised 8/31/22</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Site Development Permit Package SDP 2021-0029 &#8211; Landscape Plans - Prepared by DGA and last revised 8/31/22</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Site Development Permit Package SDP 2021-0029 &#8211; Civil Plans - Prepared by DGA and last revised 8/31/22</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Copies of the foregoing plans are on file with Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt" colspan="4"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Development - Landlord / Tenant Responsibility Matrix</b></font></td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-align: center; text-indent: 0.125in; vertical-align: middle" rowspan="2"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>DESCRIPTION</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom" colspan="2"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>ALLOCATION</b></font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle" rowspan="2"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Remarks</b></font></td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Landlord</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Tenant</b></font></td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="width: 65%; border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>GENERAL</b></font></td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="width: 13%; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; text-align: left; vertical-align: middle; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in">
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        </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">X&#160;</p>
        </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -0.05pt"></p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant







            Fit-out shall be designed to Meet no less than LEED-CI Gold</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Chemical







            Storage Rooms on Ground Floor (if needed by Tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hazardous







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hazardous







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hazardous







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Parking







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>SITEWORK</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Complete







            site improvement package as shown on the final approved plans</font></td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Complete







            hardscape as shown on the final approved plans</font></td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"> Telephone service to main demarcation room from local exchange carrier, size /
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
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            service from exterior to main switch room</font></td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
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            water service to Building</font></td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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            mounted exterior monument sign (if requested by Ionis)</font></td>
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        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="width: 13%; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







            framing dunnage above roof for Base Building mechanical equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







            framing stubs through roofing for future Tenant framing dunnage platforms</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







            framing dunnage above roof for Tenant equipment subject to Landlord review and approval</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
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            openings for Base Building utility risers</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Framed







            openings for Tenant utility risers within Base Building Cores</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Miscellaneous







            metals items and/or concrete pads for Base Building equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Miscellaneous







            metals items and/or concrete pads for Tenant equipment (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Seismic







            Anchorage of Tenant equipment, as required by local code</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Complete







            Roofing System</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Roofing







            penetrations for Base Building equipment/systems</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Roofing







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
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        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Walkway







            pads to Base Building equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Walkway







            pads to Tenant equipment (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>EXTERIOR</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Building







            Exterior Envelope Systems including glazed curtain wall</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Structural







            glazing and herculite door at main entry lobby to match campus aesthetic</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Loading







            dock overhead door(s)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Penthouse







            or roof screen enclosure for Base Building rooftop equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Penthouse







            or roof screen enclosure for Tenant rooftop equipment (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>COMMON AREAS</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Accessible







            main entrance with security hardware</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">First
            floor finished lobby consistent with a Class A Building</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Building







            Exterior security systems - Infrastructure for base building entrances to be included in core/shell</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Building







            Exterior security systems - Devices / card readers to be tenant supplied (if requested by tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Core
            area toilet rooms with Class A finishes.</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Interior







            signage for all Base Building rooms (as required by Code)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Interior







            wayfinding signage, building directory, room ID signage</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Loading







            dock area with dock leveler(s), 48&#8221; minimum high at raised position</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant







            Storage room demising barriers &amp; signage</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>ELEVATORS</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Building







            Passenger Elevators serving all occupied floors, with 3500# capacity</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="width: 65%; border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">One (1) 5000#
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        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="width: 13%; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Provided by tenant, to
            meet building standard (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Core and shell fire-rated
            partitions (constructed with base building)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Control Area fire ratings
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Additional toilet rooms
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 8.75pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Interconnecting







            stairs within tenant spaces (Other than Fire Stairs, subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant kitchen areas
            (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Partitions, ceilings,
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fixed and movable
            casework</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Laboratory equipment
            including, but not limited to, biosafety cabinets, autoclaves, glasswashers and bioreactors</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Chemical fume hoods,
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">All interior signage for
            Tenant Premises (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Sound attenuation
            upgrades for Tenant Premises to comply with Tenant acoustical criteria and design of Tenant Areas</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>FIRE PROTECTION</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 76pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fire
            service entrance including fire department connection, alarm valve, back flow protection, and fire pump.</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5.2pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Base







            Building area distribution piping shall have finished type sprinklers Tenant shell spaces shall have upturned heads (designed for Ordinary Hazard).</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Standpipes, distribution
            and hose connections within egress stairs, and lobby. Stair distribution piping and sprinkler heads</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">All run outs, drop heads,
            and related equipment within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Modification of sprinkler
            piping and head locations to suit Tenant layout and hazard index</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Specialized extinguishing
            systems including FM200 or pre-action dry-pipe systems within Tenant premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fire extinguisher
            cabinets</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fire extinguisher
            cabinets within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Additional hose
            connections within Tenant Premises if desired by Tenant, including distribution piping (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>PLUMBING</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 76pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Domestic







            water service with backflow prevention and Base Building risers</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Base Building restroom
            plumbing fixtures compliant with accessibility requirements</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 8.75pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Domestic







            water distribution within Tenant Premises including reduced pressure backflow preventer</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Non-potable hot water
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lab vacuum pipe risers
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 11.5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lab







            vacuum pipe distribution within Tenant Premises for specific points of use</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 76pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Natural







            gas piping from Tenant meter to Tenant Premises or Tenant equipment area</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Natural gas pipe
            distribution within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>HEATING, VENTILATION, AIR CONDITIONING</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Main electric room
            ventilation system</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Central Heating Plant</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hot water pipe risers</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Hot water pipe
            distribution within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Reheat coils within
            Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Reheat coils within Base
            Building areas</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 11.5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Building







            Management System (BMS) for Base Building, expandable to include Tenant System. Tenant spec to be provided</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
        </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Spec to be provided by Tenant at least 30 days prior to finalization of
            construction documents</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">85</font></div>
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      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in; width: 65%"> BMS (compatible with Landlord&#8217;s system) within Tenant&#8217;s Premises
          monitoring Tenant infrastructure (subject to LL review and approval). </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; width: 11%; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; width: 11%; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; width: 13%">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Restroom







            exhaust for Base Building area restrooms</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Restroom







            exhaust for new restrooms built within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Electric







            room ventilation system for Base Building electrical closets</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Electric







            room ventilation system for electrical closets within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Chemical







            storage room ventilation and exhaust systems in base building areas (if needed by Tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Chemical







            storage room ventilation and exhaust systems in tenant areas</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Sound
            attenuation for Base Building equipment to comply with Zoning Ordinance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Sound
            attenuation for Tenant equipment to comply with Zoning Ordinance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Additional/







            dedicated cooling equipment for Tenant requirements</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Central







            chilled water plant</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Chilled







            water distribution to Base Building AHU&#8217;s</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Cooling







            towers, supporting condenser water pumps and Process condenser water pipe risers piping, space cooling/heating and supplemental cooling.</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Condensor







            water piping for space heating/cooling and supplemental cooling within Tenant Premises..</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">BTU
            meters on hot water, chilled water and condenser water runouts to tenant heat pumps, and reheat coils and radiation compatible with and tied back to Landlord BMS Metering System (if requested by tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">&#160;</p>
        </td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">100%
            outdoor air supply air handling units with prefilters, final filters, chilled water coils, hot water coils</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
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      <tr style="vertical-align: top">
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          compatible with and tied back to Landlord BMS Metering system </td>
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      <tr style="vertical-align: top">
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          connections, insulation, air terminals, dampers, hangers, etc. within Tenant Premises <br>
          &#8226;&#160; Office: 0.2 CFM / SF <br>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -6.2pt"></p>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Supply







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
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      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"> Exhaust air duct distribution, exhaust air valves, equipment connections,
          insulation, air terminals, dampers, hangers, etc. within Base building Areas </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X</p>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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        <td style="width: 65%; border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"> Exhaust air duct distribution, exhaust air valves, equipment
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        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X&#160;</p>
        </td>
        <td style="width: 13%; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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            water system for tenant use</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>ELECTRICAL</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Primary







            service feed from Utility Company, electrical service switchboards and related Base Building equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">480/277V







            bus risers in electrical closets for Tenant connection</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Life
            safety generator - Base Building to provide 5 watts/sf of lab area for standby power. Sound attenuation as required by Zoning Ordinance.</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Bus
            plug, meter socket, utility meter, and disconnect for bus tie in</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Standby







            power distribution within Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lighting







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lighting







            and power distribution for Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Life
            safety emergency lighting/signage including panels and circuit breakers for Base Building areas</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Life
            safety emergency lighting/signage for Tenant Premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant







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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"> Allocation of normal bus power for Tenant use (w/USF): <br>
          &#8226;&#160;&#160;&#160;&#160;&#160; Office Power &amp; Lighting: 6.5w / SF <br>
          &#8226;&#160;&#160;&#160;&#160;&#160; Lab Power &amp; Lighting: 15w/ SF </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X&#160;</p>
        </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Standby







            natural gas generator for Tenant, including sound attenuation as required by Zoning Ordinance (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Automatic







            transfer switches for Tenant stand-by power load and stand-by power distribution</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>FIRE ALARM</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Base
            Building expandable voice annunciated fire alarm system with devices within Base Building areas</font></td>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
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      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Bi-Directional







            Radio Antenna for Fire Fighter Communications</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Fire
            alarm sub panels and devices for Tenant Premises with integration into Base Building system</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Alteration







            to fire alarm system to facilitate Tenant program</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>TELEPHONE/DATA</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Underground







            local exchange carrier service to primary demarcation room</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tel/data







            riser closet</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Vertical







            pathways from primary demarcation room to Tel/Data riser closets on each floor</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt; text-align: center; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant







            tel/data rooms</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pathways







            from Tel/Data riser closets into Tenant Premises (subject to LL review and approval)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tel/data







            cabling including copper and fiber-optic (from demarcation rooms to Tenant Premises tel/data rooms including vertical risers)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tel/data







            infrastructure including, but not limited to, servers, computers, phone systems, switches, routers, MUX panels, racks, ladder racks, HVAC, etc.</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Provisioning







            of circuits and service from service providers</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Audio
            visual systems and support</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; text-indent: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Station







            cabling from Tenant tel./data room to all Tenant locations, within the suite and exterior to the suite, if needed</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">87</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 65%; border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Common area and exterior area WIFI coverage</font></td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="width: 11%; border-bottom: black 1pt solid; border-right: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="width: 13%; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Tenant







            area WIFI coverage</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top; background-color: #BEBEBE">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>SECURITY</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-left: 0.125in; padding-right: 5pt; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Card
            access to Building entries, elevators and stairs</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Card
            access into or within Tenant Premises on separate Tenant installed and managed system</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-align: justify; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Video camera coverage of exterior premises including building entries and loading dock, compatible with and integrated into Tenant security system. (if requested by tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">X&#160;</p>
        </td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 0.125in; text-indent: 0.125in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Video
            camera coverage of Tenant Premises on separate Tenant installed and managed system (if requested by tenant)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: middle">&#160;</td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; text-align: center; padding-right: 5pt; vertical-align: middle"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">X</font></td>
        <td style="border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center">&#160;</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">88</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 3</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">DEVELOPMENT SCHEDULE</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[TO BE ATTACHED]</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">89</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">90</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin-top: 0pt; text-align: center; margin-bottom: 0pt">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">91</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <!--PROfilePageNumberReset%Num%92%%%-->
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 4</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">TENANT IMPROVEMENT DESIGN MILESTONES</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" align="CENTER" style="width: 80%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 70%">100% Schematic Design</td>
        <td style="width: 30%">March 7, 2023</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <table cellspacing="0" cellpadding="0" border="0" align="CENTER" style="width: 80%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 70%">100% Design Development</td>
        <td style="width: 30%">May 1, 2023</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <table cellspacing="0" cellpadding="0" border="0" align="CENTER" style="width: 80%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 70%">85% Construction Documents (Permit Submittal)</td>
        <td style="width: 30%">July 3, 2023</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <table cellspacing="0" cellpadding="0" border="0" align="CENTER" style="width: 80%; margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 70%">100% Construction Documents</td>
        <td style="width: 30%">August 4, 2023</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">92</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 5</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">TENANT IMPROVEMENT PROGRAM</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">The program for the Tenant Improvements shall be compatible in all respects with the Fundamental Requirements, provide for the improvements necessary for full occupancy of the Premises,
    and otherwise be consistent with first-class office and laboratory use, with ancillary uses as permitted pursuant to the Permitted Use. The Tenant program shall provide for fit and finishes consistent with, or of a better quality than, Tenant&#8217;s
    existing office and laboratory premises located at 2855 Gazelle Ct., Carlsbad, California. The fit plan attached is representative of the scope and nature of the Tenant Improvements.</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">93</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>[***]</b></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">94</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>[***]</b></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">95</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>[***]</b></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">96</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>[***]</b></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">97</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 6</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">PRELIMINARY BUDGET</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">98</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: bottom">
        <td style="width: 44%; border-top: Black 1pt solid; font-weight: bold">Cost Item</td>
        <td style="width: 18%; border-top: Black 1pt solid; font-weight: bold; text-align: center">Ref</td>
        <td style="width: 20%; border-top: Black 1pt solid; font-weight: bold; text-align: center">Preliminary Estimate</td>
        <td style="width: 18%; border-top: Black 1pt solid; font-weight: bold; text-align: center">$PSF</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; padding-left: 0.125in">Land Acquisition</td>
        <td style="vertical-align: top; border-top: Black 1pt solid; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: center">33,000,000</td>
        <td style="vertical-align: bottom; border-top: Black 1pt solid; text-align: center">200</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; padding-left: 0.125in">Closing Costs Allocation</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">330,000</td>
        <td style="vertical-align: bottom; text-align: center">2</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-left: 0.125in">Soft Costs</td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">8,352,652</td>
        <td style="text-align: center">51</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; padding-left: 0.125in">Hard Costs</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">94,878,874</td>
        <td style="vertical-align: bottom; text-align: center">576</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; padding-left: 0.125in">Landlord Tenant Improvement Allowance</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">41,208,250</td>
        <td style="vertical-align: bottom; text-align: center">250</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-left: 0.125in">Development Fee<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">(1)</sup></td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">3,921,111</td>
        <td style="text-align: center">24</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-left: 0.125in">Oxford Overhead</td>
        <td style="text-align: center">&#160;</td>
        <td style="text-align: center">1,300,000</td>
        <td style="text-align: center">8</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; padding-left: 0.125in">Operating Shortfall</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">2,607,603</td>
        <td style="vertical-align: bottom; text-align: center">16</td>
      </tr>
      <tr>
        <td style="vertical-align: bottom; padding-left: 0.125in">Financing Costs</td>
        <td style="vertical-align: top; text-align: center">&#160;</td>
        <td style="vertical-align: bottom; text-align: center">12,407,982</td>
        <td style="vertical-align: bottom; text-align: center">75</td>
      </tr>
      <tr style="vertical-align: bottom">
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; padding-bottom: 1pt; font-weight: bold">Total Budget</td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; padding-bottom: 1pt; font-weight: bold; text-align: center">(A)</td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; font-weight: bold; text-align: center">198,006,472</td>
        <td style="border-top: Black 1pt solid; border-bottom: Black 1pt solid; font-weight: bold; text-align: center">1,201</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">99</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>SCHEDULE 7</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">DELIVERY CONDITION</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">1.</font></td>
        <td style="text-align: justify">The Building becomes &#8220;dried in&#8221; meaning that is a water tight shell.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">2.</font></td>
        <td style="text-align: justify">As part of Tenant&#8217;s schematic document submission to Landlord for the Tenant Improvements, Tenant shall identify any locations (not to exceed a reasonable number) where Tenant desires to place deck inserts on each
          floor of the Premises to accommodate Tenant&#8217;s internal staircases or similar, customary items consistent with comparable first- class buildings used for life sciences purposes. Landlord shall cooperate and collaborate with Tenant to allow for the
          installation of such approved deck inserts, if any, prior to the occurrence of Delivery Condition, subject to agreeing with Tenant on the minimum amount of Tenant Delay resulting from the same and the other terms and conditions of the Work
          Letter.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">3.</font></td>
        <td style="text-align: justify">Tenant shall have safe and reasonably efficient access to the work site.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">4.</font></td>
        <td style="text-align: justify">Installation of floors should be sufficiently complete to allow layout to begin of floor surfaces, column lines, control lines or (to the extent applicable) Trimble reference points. Any stored material for
          Landlord&#8217;s Construction Work (including turnover attic stock) must be located outside of the building (on site), or in an area or areas on each applicable floor designated by the General Contractor that permit the orderly progress of Tenant
          Improvements.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">5.</font></td>
        <td style="text-align: justify">Site access is available, as reasonably designated by the General Contractor, for efficient material delivery and Building loading.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">6.</font></td>
        <td style="text-align: justify">Site access is available for the Tenant Improvement contractor and subcontractor&#8217;s construction trailer (if applicable) and laydown space in a location reasonably designated by the General Contractor.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">7.</font></td>
        <td style="text-align: justify">Permanent electrical service is available to the Premises and Building, with sufficient capacity to power small tools, temporary lighting and equipment to provide temporary ventilation/heating to perform the Tenant
          Improvements using normal means of power use. Electrical rooms within the Premises to be constructed as part of the Landlord&#8217;s Construction Work are accessible for performance of the Tenant Improvements, should Tenant Improvements be required in
          those areas.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">8.</font></td>
        <td style="text-align: justify">Tenant&#8217;s Contractor has ability to terminate electrical wires in electrical panels installed as part of the Landlord&#8217;s Construction Work.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">9.</font></td>
        <td style="text-align: justify">All base Building shafts within the Premises are installed.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in; text-align: left"><font style="font-family: Times New Roman, Times, Serif">10.</font></td>
        <td style="text-align: justify">Tenant&#8217;s contractor is able to use fire stairs to travel to and from the street level and between each Tenant floor. Use of stairs subject to coordination with Landlord&#8217;s completion of finishes and inspections of the
          stairs. Completion of and ability to connect Landlord-provided wet stacks (vent, sanitary, storm) to the extent included within Landlord&#8217;s Construction Work, subject to any required government approvals.</td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">11.</font></td>
        <td style="text-align: justify">Fire Life Safety systems (fire sprinkler, fire alarm) are complete and able to be tied into by the Tenant Improvement contractor.</td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">100</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">12.</font></td>
        <td style="text-align: justify; padding-right: 80.05pt">At least one elevator is available for Tenant Improvement contractor use in coordination with the General Contractor.</td>
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  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><u>Schedule 8</u></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>Minimum Vertical MEP Infrastructure Standards</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Must include the following:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Tenant will size the following spaces to accommodate equipment for a 50/50 lab office ratio given the &#8220;Typical San Diego Life Science Tenant MEP Performance Table&#8221; set forth below for the
    following areas: service yard for generator; sizing for main electrical room; floor level electrical room sizing and risers; plumbing site connections for sanitary, storm, domestic water and natural gas (if code allows); plumbing room sizing; service
    yard sizing for cooling towers; mechanical room sizing for chillers, boilers and air handling units; roof area allocated for MEP equipment; mechanical shaft sizes/locations &#8211; supply air, lab exhaust air, restroom exhaust and office return air.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Tenant agrees to meet the typical 50/50 lab office ratio minimum for cooling tonnage listed in the &#8220;Typical San Diego Life Science Tenant MEP Performance Table&#8221; (1163 tons), which
    includes sizing of the chillers, cooling tower/s, chiller pumps, chill water piping (upstream of the air handling units), insulation and associated electrical services to the equipment listed above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Tenant agrees to meet the typical 50/50 lab office ratio minimum for heating loads listed in the &#8220;Typical San Diego Life Science Tenant MEP Performance Table&#8221; (5830 MBH), which includes
    sizing of heating hot water boilers, heating hot water pumps, heating hot water piping (upstream of the air handling units), insultation and associated electrical services to the equipment listed above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">May include the following (&#8220;Tenant Optional MEP Infrastructure&#8221;):</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Tenant may, but shall not be required to, meet the minimum supply and exhaust CFM/SF per the &#8220;Typical San Diego Life Science Tenant MEP Performance Table&#8221;. All ductwork and its
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><u>Typical San Diego Life Science Tenant MEP Performance Table</u></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
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        <td style="width: 16%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Cooling Tons</font></td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Lab Office Ratio</p>
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        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-left: 5pt; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5357</font></td>
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      <tr style="vertical-align: top">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">To the extent that the Approved Core and Shall Plans do not contain any of the Tenant Optional MEP Infrastructure, then Landlord shall have the option to either (1) on or before the first
    to occur of (x) the date that is 90 days following the Tenant&#8217;s final approval of the Approved Core and Shell Plans or (y) the date that is fifteen (15) days following Tenant&#8217;s delivery of the schematic design phase of the TI Plans to Landlord, notify
    Tenant in writing of Landlord&#8217;s election pursuant to this clause (1) and thereafter cause the Architect to modify the Approved Core and Shell Plans to include such Tenant Optional MEP Infrastructure as Landlord may elect and the General Contractor to
    construct the same as part of the Landlord&#8217;s Construction Work (but such costs shall not be included within the Construction Costs) (any such changes being deemed to be Shell and Core Permitted Changes), or (2) notwithstanding anything in the Lease to
    the contrary, in the event that the Lease terminates prior to the scheduled expiration date, draw on the Letter of Credit in whole or in part, as Landlord elects, from time to time and use the funds so drawn to design and construct all or any part of
    the Tenant Optional MEP Infrastructure not included within the Approved Core and Shell Plans. The provisions of this paragraph shall survive the termination or earlier expiration of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">EXHIBIT C</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>FORM OF TENANT ESTOPPEL CERTIFICATE</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The undersigned as Tenant under that certain Lease Agreement (the &#8220;<b>Lease</b>&#8221;) made and entered into as of _________,with LOTS 21 &amp; 22
    OWNER (DE) LLC, a Delaware limited liability company, as Landlord, for the Building, land, and parking facilities located at 2850, 2855 &amp; 2859 Gazelle Court, Carlsbad, California (the &#8220;<b>Premises</b>&#8221;), certifies as follows:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Attached hereto as <u>Exhibit A</u> is a true and correct copy of
    the Lease and all amendments and modifications thereto. The documents contained in <u>Exhibit A</u> represent the entire agreement between the parties as to the leasing of the Premises. Capitalized terms used but not defined herein have the meanings
    ascribed to them in the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The undersigned has commenced occupancy of the Premises described in
    the Lease, currently occupies the Premises, and the Term commenced on _____________, 20___.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Lease is in full force and effect and has not been modified,
    supplemented or amended in any way except as provided in <u>Exhibit A</u>. Tenant is not entitled to receive any concession or benefit (rental or otherwise) or other similar compensation in connection with leasing the Premises other than as set forth
    in the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant has not transferred, assigned, or sublet any portion of the Premises
      nor entered into any license or concession agreements with respect thereto except as follows __________________________.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 267.95pt">&#160;</p>
  <p style="text-align: justify; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"> 5. &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Rent became payable on ______________, 20___.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"> 6. &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The current Term expires on ______________, 20___.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">7.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The Lease is enforceable and neither Tenant nor, to Tenant&#8217;s actual
    knowledge, Landlord is in default thereunder except as follows: _______________________. Without limiting the foregoing, (i) all construction and installation of tenant improvements required to be performed by or paid by Landlord under the Lease have
    been completed and paid and (ii) there are no unpaid allowances or rental concessions payable or creditable to Tenant which have not been paid or credited in full, except as follows: _______________________.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"> 8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; No rental has been paid in advance.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">9.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>As of the date hereof, Tenant has no presently exercisable defenses
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">10.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>All monthly installments of Base Rent, Additional Rent, and Taxes have
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">11.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Except for the Right of First Negotiation granted to Tenant pursuant
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    Lease.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">12.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>The amount of the Security Deposit held by Landlord, to secure
    Tenant&#8217;s performance under the Lease is _____________ Dollars ($__________). No portion of the Security Deposit has been utilized or applied by Landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">13.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant is not the subject of any bankruptcy, insolvency, debtor&#8217;s
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The undersigned acknowledges that this Estoppel Certificate may be delivered to Landlord&#8217;s prospective mortgagee, trust deed holder or a
    prospective purchaser or investor, and acknowledges that it recognizes that if same is done, in addition to Landlord, said mortgagee, prospective mortgagee, trust deed holder or prospective purchaser or investor will be relying upon the statements
    contained herein in making the loan or acquiring the Premises, and in accepting an assignment of the Lease as collateral security, and that receipt by it of this Estoppel Certificate is a condition of making the loan or acquisition of the Premises.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">If Tenant is a corporation, limited liability company or partnership, each individual executing this Estoppel Certificate on behalf of Tenant
    hereby represents and warrants that Tenant is a duly formed and existing entity qualified to do business in the State of California, if required by law, and that Tenant has full right and authority to execute and deliver this Estoppel Certificate and
    that each person signing on behalf of Tenant is authorized to do so.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Tenant, by providing this Estoppel Certificate, does not waive (i) any of its claims, defenses, offsets, or rights against Landlord discovered
    after the date hereof, or (ii) any of Tenant&#8217;s rights first arising after the date hereof provided by any federal, state or local laws, ordinances, rules and regulations, court orders, governmental directives and governmental orders and all
    interpretations of the foregoing.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Nothing in this Estoppel Certificate shall be deemed to amend, modify or alter the Lease and in the event of any conflict between the Lease and
    this Estoppel Certificate, the Lease shall prevail. This Estoppel Certificate is delivered in good faith and shall not subject Tenant or the individual signatory to any liability (other than estoppel effect) for any purpose, including, without
    limitation, damages for inaccuracies, errors or omissions, except to the extent resulting from fraud or an intentional and material misstatement of fact.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><i>[Remainder of page intentionally left blank]</i></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"><font style="font-size: 10pt">Executed at ____________on the _______ day of ________________, 20____.</font></p>
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        <td style="width: 1%">&#160;</td>
        <td style="width: 1%">&#160;</td>
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        <td style="border-bottom: Black 1pt solid">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">EXHIBIT D</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>FORM OF MEMORANDUM OF LEASE</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0in; text-align: justify; text-indent: 0.5in">This Memorandum of Lease (this &#8220;<b>Memorandum of Lease</b>&#8221;) is made as of this [&#160;&#160;&#160; ]day _____ of [&#160;______] , 20__, by and between LOTS 21
    &amp; 22 OWNER (DE) LLC, a Delaware limited liability company with its principal mailing address of [__] (&#8220;<b>Landlord</b>&#8221;), and IONIS PHARMACEUTICALS, INC., a Delaware corporation, with its principal mailing address of [ ____________ ] (&#8220;<b>Tenant</b>&#8221;).






    All capitalized terms not otherwise defined herein shall have the meaning ascribed to such term in the Lease (as defined below).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Premises</u>. Landlord owns and leases, demises and grants to
    Tenant, and Tenant leases from Landlord, that certain real property located at 2850, 2855 &amp; 2859 Gazelle Court, Carlsbad, California, 92010, as more particularly described on <u>Schedule A</u> attached hereto and made a part hereof (the &#8220;<b>Leased
      Premises</b>&#8221;) pursuant to the terms, covenants and conditions of that certain Lease Agreement dated as of ____________, 20__ (the &#8220;<b>Lease</b>&#8221;). Capitalized terms used herein shall have the same meaning as set forth in the Lease, except to the
    extent such terms are specifically defined in this Memorandum of Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Term</u>. The initial Term of the Lease shall be for a period of
    fifteen (15) years commencing on [ _________], [20__] and expiring on the last day of the one hundred eightieth (180th) full calendar month next following such date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Option to Extend</u>. Landlord grants to Tenant the option to
    extend the term of the Lease at the expiration of the Initial Term for two (2) successive periods of five (5) years each, aggregating twenty (10) years. Each such renewal option must be exercised no later than twelve (12) months prior to the expiration
    of the initial Term or the then-current Renewal Term.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Successors and Assigns</u>. The conditions and provisions hereof
    shall inure to the benefit of and shall be binding upon Landlord, Tenant, and their respective successors and assigns, and shall run with the land.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">5.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Memorandum</u>. The rentals to be paid by Tenant and all of the
    obligations and rights of Landlord and Tenant are set forth in the Lease. This Memorandum of Lease is merely a memorandum of the Lease and is subject to all of its terms, conditions and provisions. In the event of any inconsistency between the terms of
    the Lease and this Memorandum of Lease, the terms, covenants and conditions of the Lease shall prevail.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">6.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Counterparts</u>. This Memorandum of Lease may be executed in any
    number of counterparts, each of which shall be an original, but all of which shall together constitute one and the same document.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: italic bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[No further text on this page. Signature page to follow.]</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in">IN WITNESS WHEREOF, Landlord has caused its duly authorized officer to execute this Memorandum of Lease as of the date first noted above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in">&#160;</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">LOTS 21 &amp; 22 OWNER (DE) LLC, a</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Delaware limited liability company&#160;</p>
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  <p style="margin: 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
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        <td style="width: 40%">By:&#160;______________________________________ [SEAL]</td>
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        <td>Name: ___________________________________</td>
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  <p style="margin: 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">STATE/COMMONWEALTH OF _________________)</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">CITY/COUNTY OF _________________) &#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0.25in 0pt 0.5in; text-align: justify">On the __ day of <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#160;&#160;&#160;&#160;&#160;&#160;&#160;</u> in the year 20__, before me, the undersigned, a Notary Public in and for said state, personally appeared
    <u>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</u>, personally known to me or proved to me on the basis of satisfactory evidence to be the individual whose name is subscribed to the within instrument, and acknowledged to me that he executed the same
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">My Commission Expires:______________________________</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in">IN WITNESS WHEREOF, Tenant has caused its duly authorized officer to execute this Memorandum of Lease as of the date first noted above.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 60%">&#160;</td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">TENANT:</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">IONIS PHARMACEUTICALS, INC., a&#160;</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
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        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>By&#160;:______________________________________ </td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>Name: ___________________________________</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>Title:_____________________________________</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 50%; border: Black 1pt solid; padding-right: 5pt; padding-left: 5pt">A notary public or other officer completing this certificate verifies only the identity of the individual who signed the document to which this certificate is
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

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        <td style="width: 27%">STATE OF CALIFORNIA</td>
        <td style="width: 73%">)</td>
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      <tr style="vertical-align: top; text-align: left">
        <td>&#160;</td>
        <td>) &#167;</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 219pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">On ______________________, before me, ______________________________ a Notary Public, personally appeared ___________________________ who proved to me on the basis of satisfactory
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">I certify under PENALTY OF PERJURY under the laws of the State of California that the foregoing paragraph is true and correct</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">WITNESS my hand and official seal.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">________________________________________</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: -0.05pt">Schedule A to <br>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[to be attached]</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><b>EXHIBIT E <br>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><b>FORM OF SNDA</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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  <p style="margin: 0pt 0"></p>
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  <p style="margin: 0pt 0"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Attention: _________________________________</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">SPACE ABOVE THIS LINE FOR RECORDER&#8217;S USE</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 100%; text-align: center; border: Black 1pt solid; padding-bottom: 10pt"><b>SUBORDINATION, NON-DISTURBANCE AND ATTORNMENT AGREEMENT</b></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">This SUBORDINATION, NON-DISTURBANCE AND ATTORNMENT AGREEMENT (hereafter referred to as &#8220;<u>Agreement</u>&#8221;) made as of _______________, 2022, by
    and between ______________, having an address at , as administrative agent (with its successors or assigns, &#8220;Agent&#8221;) for itself and certain lenders now or hereafter party to the Loan Agreement (as hereinafter defined) (the &#8220;<u>Lenders</u>&#8221;),
    ______________, a ______________, having an address of _____________ (&#8220;Tenant&#8221;) and _____________, a ______________, having an address at __________ (&#8220;<u>Landlord</u>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">The Lenders have made a loan to Landlord in the maximum principal amount of $______________ in accordance with the terms of that certain [Loan
    Agreement] dated as of __________, 2022 (the &#8220;Loan&#8221;), by and among Landlord, Agent and Lenders (as the same may hereafter be amended, reinstated, extended, supplemented or otherwise modified from time to time, the &#8220;<u>Loan Agreement</u>&#8221;),</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Pursuant to the Loan Agreement, the Agent, for the benefit of the Lenders, is the holder of a certain [Deed of Trust, Security Agreement,
    Assignment of Leases and Rents, and Fixture Filing] (as the same may be amended, extended, supplemented or otherwise modified or restated from time to time, the &#8220;<u>Security Instrument</u>&#8221;) granted by Landlord to Agent, for the benefit of the Lenders,
    and recorded in the official records of San Diego County, California, which constitutes a first lien against the real property described on <u>Schedule A</u> attached hereto and the improvements thereon or to be constructed thereon (the &#8220;<u>Property</u>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Tenant has entered into a lease with Landlord dated as of __________, 2022 (the &#8220;<u>Lease</u>&#8221;) covering all of the Property (the &#8220;<u>Premises</u>&#8221;).






    All capitalized terms used but not defined in this Agreement shall have the meanings set forth in the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">For mutual consideration, including relying on the mutual covenants and agreements contained in this Agreement, the receipt and sufficiency of
    which are hereby acknowledged, Agent, Landlord and Tenant agree as follows:</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">111</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Subordination of Lease</b>. Subject to the terms of this Agreement,
    the Lease and all of Tenant&#8217;s right, title, and interest in and to the Property thereunder (including, but not limited to, any option to purchase, right of first refusal to purchase, or right of first offer to purchase the Property or any portion
    thereof) is and shall be subject and subordinate to the Security Instrument and to all present and future advances under the obligations secured thereby and all renewals, amendments, modifications, consolidations, replacements and extensions thereof,
    to the full extent of the principal amount and other sums secured thereby and interest thereon, so that at all times the Security Instrument shall be and remain a lien on the Property prior to and superior to the Lease for all purposes, subject to the
    provisions set forth in this Agreement. Such subordination shall have the same force and effect as if the Security Instrument and such renewals, modifications, consolidations, replacements and extensions of the Security Instrument had been executed,
    acknowledged, delivered and recorded prior to the Lease, all amendments or modifications of the Lease, and any notice of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>2.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Attornment</b>. Tenant will attorn to and recognize: (i) Agent
    (including for this purpose any transferee or nominee of Agent), whether as mortgagee in possession or otherwise; or (ii) any purchaser at a foreclosure sale under the Security Instrument; or (iii) any transferee that acquires possession of or title to
    the Property (whether by acceptance of a deed in lieu of foreclosure or otherwise); or (iv) any successors and assigns of such purchasers and/or transferees (each of the foregoing persons or entities described in clauses (i) through (iv) above, a &#8220;<u>Successor</u>&#8221;),






    as its landlord for the unexpired balance (and any extensions, if exercised) of the term of the Lease upon the terms and conditions set forth in the Lease (as affected by this Agreement), and Tenant shall pay and perform in favor of Successor all of
    the obligations of Tenant under the Lease as if Successor were the original lessor under the Lease. Such attornment shall be effective and self- operative without the execution of any further instruments by any party hereto; <u>provided</u>, <u>however</u>,
    that Tenant will, upon request by Agent or any Successor, execute a reasonable written agreement attorning to Agent or such Successor, which agreement shall, in any event, be subject to the terms and provisions of this Agreement.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>3.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Non-Disturbance</b>. So long as the Lease is in effect and Tenant
    complies with Tenant&#8217;s obligations under this Agreement and is not in default (beyond the expiration of any applicable cure period) under the Lease, Agent and any Successor (i) will recognize the Lease and Tenant&#8217;s rights and options under the Lease as
    the tenant of the Premises for the remainder of the term of the Lease (as affected by this Agreement), including any extension options, if exercised, and (ii) will not disturb Tenant&#8217;s use, possession and quiet enjoyment of the Premises, nor will
    Tenant&#8217;s rights under this Lease be impaired (except as provided in this Agreement), and (iii) shall not name or join Tenant as a defendant in any foreclosure action, sale under a power of sale or transfer in lieu of the foregoing (collectively, a &#8220;<u>Foreclosure</u>&#8221;)






    unless a joinder is required by law to perfect a Foreclosure or other remedy, but then only for such purpose and not for the purpose of terminating the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>4.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Assignment of Leases</b>. Tenant acknowledges that it has been
    advised that Landlord has assigned the Lease and the rents thereunder to Agent, for the benefit of the Lenders, pursuant to the Security Instrument. Tenant acknowledges that the interest of the Landlord under the Lease is to be assigned to Agent solely
    as security for the purposes specified in the Security Instrument, and, on account of the Security Instrument, Agent shall have no duty, liability or obligation whatsoever under the Lease or any extension or renewal thereof, either by virtue of the
    Security Instrument or by any subsequent receipt or collection of rents thereunder, unless Agent shall specifically undertake such liability in writing. The foregoing agreement by Tenant shall not adversely affect any rights of Tenant under the Lease
    with respect to the Landlord in the event of nonperformance by Landlord, subject to the terms of this Agreement. Tenant agrees that if Agent, pursuant to the Security Instrument, and whether or not it becomes a mortgagee in possession, shall give
    written notice to Tenant that Agent has elected to require Tenant to pay to Agent the rent and other charges payable by Tenant under the Lease, Tenant shall (without any duty to inquire as to the enforceability or validity of Agent&#8217;s notice) until
    Agent shall have canceled such election in writing, thereafter pay to Agent all rent and other sums payable under the Lease and such payments to Agent shall be treated as payments made under the Lease. Any such payment shall be made notwithstanding any
    right of setoff, defense or counterclaim which Tenant may have against Landlord, or any right to terminate the Lease. Landlord authorizes and directs Tenant to immediately and continuously make all such payments at the direction of Agent, releases
    Tenant of any and all liability to Landlord for any and all payments so made, and agrees that payments actually made by Tenant to Agent shall be credited towards the amounts due under the Lease.</p>
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    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">112</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>5.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Limitation of Liability</b>. In the event that Agent (including for
    this purpose any transferee or nominee of Agent) or any other Successor succeeds to the interest of Landlord under the Lease, or title to the Property, then none of Agent, any Lender or any Successor shall be: (i) liable in any way to Tenant for any
    act or omission, neglect or default on the part of any prior landlord under the Lease; <u>provided</u>, that, nothing in this clause being deemed to relieve Agent or any Successor of an ongoing default on the part of Landlord with respect to repair
    and maintenance of the Premises that first arose prior to such succession, provided that Tenant notified Agent of such default in accordance with Section 7 of this Agreement and Agent failed to cure same and Agent or any Successor shall have the
    obligation to cure such ongoing repair and maintenance defaults on the part of Landlord that continue from and after Successor succeeds to the rights of Landlord under the Lease, regardless of when such default or obligation from arose, provided that
    Tenant notified Agent of such default in accordance with Section 7 of this Agreement and Agent failed to cure same; (ii) responsible for any monies (including security deposits) owing by or on deposit with (or any letter of credit on deposit with)
    Landlord to the credit of Tenant (except to the extent any such deposit or letter of credit is actually received by Agent or such Successor, as applicable); (iii) subject to any defense, counterclaim or setoff which theretofore accrued to Tenant
    against any prior landlord; provided, however, that the foregoing shall not limit Tenant&#8217;s right to exercise against Agent or such Successor any offset right otherwise available to Tenant because of events occurring after the date of succession and
    attornment; (iv) bound by any termination, amendment or modification, or assignment/subletting of the Lease after the date hereof (unless Agent expressly approved in writing such termination, amendment or modification, or assignment or subletting or
    the same does not require the Agent&#8217;s approval pursuant to the terms of the Loan Agreement) of the Lease (provided that, (A) as it relates to any assignments/subletting of Lease undertaken in connection with the terms and provisions set forth in the
    Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (B) no such approval shall be required with respect to amendments solely evidencing the exercise of Tenant&#8217;s option to extend the Lease and assignments or
    sublets that do not require the consent of the Landlord pursuant to the terms of the Lease); (v) bound by any previous prepayment of rent for more than one (1) month of the date due, which was not approved in writing by Agent ;(vi) required after a
    fire, casualty or condemnation of the Property or Premises to repair or rebuild the same to the extent that such repair or rebuilding requires funds in excess of the insurance or condemnation proceeds specifically allocable to the Premises and arising
    out of such fire, casualty or condemnation which have actually been received by Agent, and then only to the extent required by the terms of the Lease (Agent acknowledging that the exercise by Tenant of its remedies pursuant to Article 9 of the Lease
    are unaffected by the provisions of this clause (vi)), (vii) be liable for or incur any obligation with respect to any representations or warranties made by Landlord under the Lease; (viii) liable beyond Agent&#8217;s, such Lender&#8217;s, or such Successor&#8217;s, as
    applicable, interest in the Property and in the rents, proceeds and profits therefrom; or (ix) except as expressly provided below, responsible for any obligation of Landlord to undertake or complete any work or fund any allowance for tenant
    improvements.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">Furthermore, notwithstanding anything to the contrary contained in this Agreement (except as set forth in the immediately following paragraph) or
    the Lease, no Agent, Lender or Successor shall have any obligation to undertake or complete any of the Landlord&#8217;s Construction Work (as defined in the Lease) or advance the TI Allowance (as defined in the Lease) after it succeeds to the interest of
    Landlord under the Lease or title to the Property (collectively, the &#8220;<u>Landlord Work Obligations</u>&#8221;).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>[Only applicable prior to the occurrence of Substantial Completion under the Lease:] </b>Notwithstanding the foregoing, if the Landlord Work
    Obligations have not been fulfilled in accordance with the terms and provisions of the Lease, then Agent or Successor (as applicable) shall have thirty (30) days from the earlier of the date on which either of the following occur (the &#8220;<u>Succession
      Date</u>&#8221;): (i) Agent or any Successor (as applicable) provides written notice to the Tenant that Agent or Successor (as applicable) has succeeded to the interest of Landlord under the Lease, or (ii) Agent or Successor (as applicable) has taken title
    to the Property, to send written notice (the &#8220;<u>Intention Notice</u>&#8221;) to Tenant stating whether or not Agent or such Successor intends to fulfill the remaining Landlord Work Obligations under the Lease (which may include fulfillment of the obligation
    to complete the Landlord&#8217;s Construction Work without fulfilling the obligation to fund the TI Allowance or vice versa). If and to the extent in such Intention Notice Agent or such Successor (as applicable) states that Agent or such Successor intends to
    be so bound, then such provisions of the Lease shall be binding on the Agent or such Successor (as applicable). If in such Intention Notice Agent or Successor (as applicable) states in writing that it does not intend to be so bound with respect to the
    Landlord&#8217;s Construction Work or fails to timely provide such Intention Notice to Tenant within such thirty (30) day period, then Tenant shall have the right, by giving a notice to the Agent or such Successor (as applicable) (the &#8220;<u>Succession Election
      Notice</u>&#8221;) within sixty (60) days following the Intention Notice, or if no Intention Notice has been delivered, within sixty (60) days of the Succession Date, to, subject to compliance with the Tenant Completion Conditions (as defined below),
    complete the Landlord&#8217;s Construction Work at its expense in accordance with the terms and conditions of the Lease (in which case Base Rent shall be determined based on amounts previously expended by Landlord for Construction Costs plus any TI Allowance
    funded by Agent or such Successor, and otherwise in accordance with the Lease), and if Agent or Successor (as applicable) agreed to complete the Landlord&#8217;s Construction Work but declined to fund any remaining TI Allowance, exercise its right pursuant
    to the Lease to deduct the remaining amount of TI Allowance when due from Base Rent in accordance therewith to the extent the same has been included in the calculation of Base Rent under the Lease, until the full amount of TI Allowance included within
    the Base Rent is recouped by Tenant (but without the necessity of giving any additional notices to Landlord); and further provided, however, that the Agent or Successor (as applicable) can render any Succession Election Notice null and void and of no
    force and effect if, within thirty (30) days after the giving of such Succession Election Notice, the Agent or Successor (as applicable) agrees to be bound by the applicable provisions of the Lease. Tenant&#8217;s failure to give a Succession Election Notice
    in the time period required above shall be deemed to be an election pursuant to the [clause (X)]<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">1</sup> of the immediately preceding sentence. To the extent the Tenant delivers
    the Succession Election Notice, Tenant hereby acknowledges and agrees that the Agent or Successor (as applicable) is released (except to the extent set forth in the Intention Notice and as otherwise expressly set forth in this paragraph) from any and
    all obligations under the Lease with respect to the Landlord&#8217;s Construction Work and the payment of the TI Allowance.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">As used herein, the &#8220;<u>Tenant Completion Conditions</u>&#8221; shall mean, provided that the Lender or Successor (as applicable) has not rendered any
    Succession Election Notice null and void and of no force and effect, compliance with the following conditions:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(a)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Within thirty (30) days following the delivery of the Succession
    Election Notice, if Landlord has not completed all of the Landlord Work Obligations, then Tenant shall provide reasonable evidence to Lender that Tenant has sufficient cash and other liquid assets to fulfill the Landlord Work Obligations (&#8220;<u>Tenant
      Funds</u>&#8221;);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(b)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall have entered into a contract with a person or entity (&#8220;<u>Replacement






      Manager</u>&#8221;), which Replacement Manager shall be acceptable to the Lender or Successor (as applicable) as determined in Lender&#8217;s or Successor&#8217;s (as applicable) reasonable discretion, that is qualified and experienced in the development of properties
    and construction of improvements which are of similar type and nature to the improvements contemplated to have been constructed by Landlord pursuant to the Approved Shell and Core Plans (as defined in the Lease);</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(c)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall provide Lender or Successor (as applicable) each month
    through the completion of the Landlord Work Obligations, with the following: (i) the opportunity for Lender to hold an inspection by Lender&#8217;s or Successor&#8217;s (as applicable) construction consultant, confirming the work as to which each contractor seeks
    payment is in compliance with the Approved Shell and Core Plans, (ii) a copy of contractor&#8217;s application for payment to Tenant and signed by Tenant&#8217;s architect on AIA Forms G702 and G703/G703A or other forms acceptable to Lender or Successor (as
    applicable) and confirmed by Lender&#8217;s or Successor&#8217;s (as applicable) inspector, (iii) if requested by Lender or Successor (as applicable), paid invoices or receipts and unconditional statutory lien waivers for all construction work and costs included
    in the previous request for advance, (iv) if requested by Lender or Successor (as applicable), evidence that any inspection required by any governmental authority has been completed with results satisfactory to that governmental authority, (v) such
    certifications of job progress by Tenant&#8217;s architect, in form satisfactory to Lender or Successor (as applicable), as Lender or Successor (as applicable) may request, and (vi) such other conditions as are contained within the Loan Agreement and
    customary in the administration of a construction loan of a size and type as the one evidenced by the Loan Agreement;&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0">_____________________</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">(d)<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant shall complete Landlord Work Obligations by <b>[NTD: will be
      the completion date established under the core/shell contract:] </b>___________, subject to extensions for Force Majeure;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">If Tenant fails to comply with any Tenant Completion Condition, Lender or Successor (as applicable) shall provide Tenant with written notice of
    Tenant&#8217;s failure to comply therewith and if Tenant fails to cure such non-compliance within thirty (30) days of receipt of written notice thereof (or such reasonable additional time if the cure cannot reasonably be completed within such 30-day period
    and Tenant has commenced to cure such non-compliance within such 30-day period and thereafter diligently pursues such cure), the Lender shall be entitled to either (i) terminate the Lease, without any liability to the Tenant whatsoever, including,
    without limitation, under the Lease or under this Agreement, or (ii) fulfill the Landlord Work Obligations.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">Tenant agrees that any person or entity which at any time hereafter becomes the landlord under the Lease, including without limitation, Agent or
    any Successor (as applicable), shall be liable only for the performance of the obligations of the landlord under the Lease that arise during the period of Agent&#8217;s or such Successor&#8217;s ownership of the Premises. Tenant further agrees that any liability
    of Agent or any Successor under the Lease shall be limited to the interest of Agent or such Successor in the Property and in the rents, proceeds and profits therefrom.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>6.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Purchase Rights</b>. Each of the parties hereto acknowledges that
    pursuant to the Lease, Tenant holds a right of first offer to purchase the property pursuant to Article 11 of the Lease (the &#8220;<u>Purchase Rights</u>&#8221;). The parties hereto agree that the Purchase Rights shall remain valid and in full force and effect,
    but subject and subordinate to the lien(s) of the Security Instrument. In the event that Agent or a Successor succeeds to the interest of Landlord under the Lease, such Purchase Rights shall not be extinguished by a Foreclosure; provided, however, that
    Agent or Successor shall not be bound to the Purchase Rights, and such Purchase Rights shall not apply, with respect to (i) a Foreclosure, including, without limitation, the granting of, foreclosure under, or giving of a deed-in-lieu of foreclosure
    under, a mortgage or the granting or exercise of any pledge of ownership interests, or (ii) the first subsequent sale of the Property following Agent&#8217;s or Successor&#8217;s acquisition of title to the Property, but thereafter any successor landlord to Agent
    or such Successor shall be bound by such Purchase Rights in accordance with the terms of the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>7.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Right to Cure Defaults</b>. Tenant agrees to give to Agent, either
    by certified U.S. mail (return receipt requested) or overnight courier service (i.e., FedEx), a duplicate of each notice of any default by Landlord under the Lease at the time Tenant gives such notice to Landlord, specifying the nature of such default,
    and thereupon Agent shall have the right (but not the obligation) to cure such default, and Tenant shall not exercise its remedies under the Lease unless the Tenant first gives such notice to Agent and provides Agent with notice of such default, and an
    opportunity to cure the same within a period of time that shall be not less than the period of thirty (30) days beyond any period afforded to the Landlord to cure the default under the provisions of the Lease, and a reasonable period of time in
    addition thereto (i) if the circumstances are such that said default cannot reasonably be cured within such period and Agent has commenced and is diligently pursuing such cure, plus (ii<b>)</b> a reasonable period (not to exceed 270 days unless the
    cure cannot be effected without Agent taking possession of the Property) during any litigation or enforcement action or proceeding, including a foreclosure, bankruptcy, reorganization, possessory action or a combination thereof provided that Agent or
    any Successor provides Tenant with written notice of its intent to cure such default and then proceeds diligently to cure Landlord&#8217;s default upon acquiring possession of the Premises. It is specifically agreed that Tenant shall not exercise its
    remedies under the Lease against Agent or any Successor for failure to cure any bankruptcy, insolvency or reorganization default on the part of Landlord, any breach by Landlord of any representation or warranty, or any other breach or default under the
    Lease that is personal to Landlord or otherwise not reasonably susceptible of cure by Agent or such Successor. Tenant shall accept performance by Agent of any term, covenant, condition or agreement to be performed by Landlord under the Lease with the
    same force and effect as though performed by Landlord. Without limitation on the foregoing, if the Lease is terminated for any reason other than (a) a termination which is effected unilaterally by Tenant in accordance with the express terms of the
    Lease, (b) the expiration of the term of the Lease, or (c) a termination that occurs in compliance with this Agreement, then upon Agent&#8217;s written request given within thirty (30) days after Agent receives written notice of such termination, Tenant
    shall, within fifteen (15) days after such request, execute and deliver to Agent a new lease of the Premises for the remainder of the term of the Lease, such new lease to be upon all of the same terms, covenants and conditions of the Lease applicable
    to the remainder of the term of the Lease (as affected by this Agreement).</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>8.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>Tenant&#8217;s Agreements</b>. Tenant hereby represents, warrants,
    covenants and agrees that: (i) Tenant shall not pay any rent under the Lease more than one month in advance of the date due except as expressly required in the Lease with respect to security deposits, operating expenses, taxes and the like; (ii) Tenant
    shall have no right to appear in any Foreclosure action under the Security Instrument (unless named by Agent in such action, Agent agreeing however not to name Tenant unless required pursuant to applicable laws, and then only for such purposes); (iii)
    Tenant shall not amend or modify, or assign or sublet, the Lease and Tenant shall have no right to cancel or terminate the Lease, without Agent&#8217;s prior written consent (provided that, (x) as it relates to any assignments/subletting of Lease undertaken
    in connection with the terms and provisions set forth in the Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (y) no such approval shall be required with respect to amendments solely evidencing the exercise
    of Tenant&#8217;s option to extend the Lease and assignments or sublets that do not require the consent of the Landlord pursuant to the terms of the Lease), and any attempted amendment or modification, assignment or subletting, cancellation or termination of
    the Lease in violation of the foregoing shall be of no force or effect as to Agent; (iv) Tenant shall not subordinate the Lease to any lien or encumbrance (other than the Security Instrument) without Agent&#8217;s prior written consent; (v) except as
    expressly set forth in Section 6, above, Tenant has no right or option of any nature whatsoever, whether pursuant to the Lease or otherwise, to purchase the Property, or any portion thereof or any interest therein, and to the extent that Tenant
    hereafter acquires any such additional rights or options, the same is hereby acknowledged to be subject and subordinate to the Security Instrument and is hereby waived and released as against Agent and any Successor, (vi) Tenant shall promptly, to the
    same extent and within the same time period required by the Lease, deliver to Agent, from time to time, a written estoppel statement in the form, and with the certifications, required by the Lease; (vii) this Agreement supersedes and satisfies any
    requirement in the Lease relating to the granting of a non-disturbance agreement or providing for subordination of the Lease; (viii) Tenant is the sole owner of the leasehold estate created by the Lease; (ix) the interest of Landlord under the Lease is
    assigned to Agent solely as security for the obligations secured by the Security Instrument, and neither Agent nor the Lenders shall have any duty, liability or obligation under the Lease or any extension or renewal thereof, unless Agent either (a)
    specifically undertakes such liability in writing, or (b) subject to the express terms of this Agreement, Agent becomes a Successor; (x) if this Agreement conflicts with the Lease, then this Agreement shall govern as between the parties and any
    Successor, including upon any attornment pursuant to this Agreement; and (xi) upon Agent&#8217;s transfer or assignment of Agent&#8217;s interests in the Loan, the Lease (or any new lease executed pursuant to this Agreement), or the Property, Agent shall be deemed
    released and relieved of any obligations under this Agreement, the Lease (or any new lease executed pursuant to this Agreement), and with respect to the Property.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"> <br>
  </p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"> <br>
  </p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><b>9.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font>&#160;Authority</b>. Each of Landlord, Agent, and Tenant warrants and
    represents to the other parties hereto that it has duly executed and delivered this Agreement and that the execution, delivery and performance by it of this Agreement (i) are within its powers, (ii) have been duly authorized by all requisite action,
    and (iii) do not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which it is a party or by which it or any of its property is bound.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt"> 10. &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Miscellaneous<font style="font-weight: normal">.</font></p>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.1</b> The provisions hereof shall be binding upon and inure to the benefit of Tenant and Agent and their respective successors and
    assigns, the term &#8220;Agent&#8221; as used herein includes any successor or assign of the named Agent herein, and the terms &#8220;Tenant&#8221; and &#8220;Landlord&#8221; as used herein include any successor and assign of the named Tenant and Landlord herein, respectively; provided,
    however, that such reference to Tenant&#8217;s or Landlord&#8217;s successors and assigns shall not be construed as Agent&#8217;s consent to any assignment or other transfer by Landlord in any instance where Agent&#8217;s consent to such assignment or transfer is required
    hereunder, under the Security Instrument or under any other document executed in connection therewith.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.2</b> Any notices, demands or requests to be given under this Agreement shall be in writing and shall be deemed sufficiently given
    if served personally or upon the first to occur of receipt or the refusal of delivery if mailed by United States certified mail, return receipt requested, postage prepaid, or if sent by prepaid Federal Express or other similar overnight delivery
    service which provides a receipt, addressed to the Primary Address of Landlord, Tenant, or Agent set forth below, along with copies to the applicable Supplemental Addresses set forth below, or such other address as such party may specify in writing
    from time to time;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">If to Tenant:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: left"><u>Primary Address</u><font style="font-weight: normal">:</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <!-- Field: Rule-Page -->
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    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><b><u>Supplement Addresses</u></b>:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">If to Landlord:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: left"><u>Primary Address</u><font style="font-weight: normal">:</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0"></p>
  <p style="margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><b><u>Supplement Addresses</u></b>:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0">&#160;</p>
  <p style="margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="margin: 0pt 0"></p>
  <p style="margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">If to Agent:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: left"><u>Primary Address</u><font style="font-weight: normal">:</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
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  <!-- Field: /Rule-Page -->
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><b><u>Supplement Addresses</u></b>:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
  </div>
  <!-- Field: /Rule-Page -->
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <!-- Field: Rule-Page -->
  <div align="LEFT" style="margin-left: 1in; margin-top: 0; margin-bottom: 0">
    <div style="font-size: 1pt; border-top: Black 1pt solid; width: 20%">&#160;</div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.3</b> This Agreement may not be changed, terminated, amended, supplemented, waived or modified orally or in any manner other than by
    an instrument in writing signed by the party against which enforcement of the change, termination, amendment, supplement, waiver or modification is sought.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.4</b> The captions or headings at the beginning of each paragraph hereof are for the convenience of the parties and are not part of
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.5</b> This Agreement shall be governed by and construed under the laws of the State of New York (excluding the choice of law rules
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.6</b> This Agreement represents the final agreement between the parties hereto with respect to the subject matter hereof and may not
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
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    effect.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><b>Section 10.8</b> This Agreement may be executed in one or more counterparts, each of which when so executed and delivered shall be deemed an
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[Signature Page Follows]</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>FORM OF NON-DISCLOSURE AND CONFIDENTIALITY AGREEMENT</b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>NON-DISCLOSURE AND CONFIDENTIALITY AGREEMENT</u></b></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt">WHEREAS, Ionis currently leases and occupies that certain real property located on Lots 21 &amp; 22, Whiptail Loop W in Carlsbad, 92010
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt">WHEREAS, the Parties recognize the critical importance of preserving the non-public, confidential or proprietary nature of any disclosed,
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in">NOW THEREFORE, the Parties agree, each with the other, as follows:</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in">1.<font style="font-family: Times New Roman, Times, Serif">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </font><u>Confidential Information</u>. Except as set forth in <u>Section
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    and (iii) as may be observed or obtained by Prospective Purchaser in the course of acting as landlord under the Lease (should Prospective Purchaser purchase the Property and Ionis shall continue to lease and occupy the Property pursuant to the Lease),
    including, without limitation, Trade Secret Information, any information that would reasonably be considered non-public, confidential or proprietary given the nature of the information and the Ionis Parties&#8217; businesses and all notes, analyses and other
    materials prepared by or for the Purpose that contain any of the foregoing. As used in this Agreement, &#8220;<b><i>Trade Secret Information</i></b>&#8221; means all information that is unique to Ionis&#8217; business and that is not commonly known by or available to
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    other persons who can obtain economic value from its disclosure or use; and (ii) is the subject of efforts that are reasonable under the circumstances to maintain its secrecy. The Ionis Parties&#8217; Trade Secret Information may include, but is not limited
    to, all confidential information relating to Ionis&#8217; business and operations and in the form of the Ionis Parties&#8217; research and development plans and activities; design plans; compilations of data; product plans; inventions; engineering processes and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt"> (e) &#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Ionis has agreed in writing is free of such obligations.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt">&#160;</p>
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    extent Ionis continues to lease and occupy the Property pursuant to the Lease), it is entering upon the Property for the sole purpose of evaluating a potential purchase of the Property.</p>
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    The Ionis Parties make no representation or warranty, express or implied, as to the accuracy or completeness of the Confidential Information disclosed to Prospective Purchaser hereunder. The Ionis Parties shall not be liable to Prospective Purchaser
    for any losses relating to or resulting from the Prospective Purchaser&#8217;s use of any of the Confidential Information or any errors therein or omissions therefrom.</p>
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    contrary herein, Prospective Purchaser may disclose certain Confidential Information, without violating the obligations of this Agreement, to the extent such disclosure is required by law or regulation or by a subpoena or other validly issued
    administrative or judicial process, provided that, Prospective Purchaser shall (a) provide Ionis with reasonable prompt notice of the disclosure(s) (to the extent legally permissible), (b) limit disclosure to only that portion of the Confidential
    Information which Prospective Purchaser is legally compelled to disclose and (c) reasonably cooperate in assisting Ionis (at Ionis&#8217; expense) in its efforts to ensure confidential treatment will be accorded any Confidential Information so furnished (to
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt">&#160;</p>
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      Information</u>. Prospective Purchaser&#8217;s obligations to protect any Confidential Information received from the Ionis Parties shall continue for a period of three (3) years from the date of disclosure, notwithstanding whether or not Prospective
    Purchaser purchases the Property. At Ionis&#8217; written request, so long as the same is no longer reasonably necessary for Prospective Purchaser&#8217;s use in connection with the Purpose, Prospective Purchaser shall promptly destroy all copies, whether in
    written, electronic or other form or media, of the Ionis Parties&#8217; Confidential Information and certify in writing to Ionis that such Confidential Information has been destroyed; provided that Prospective Purchaser shall not be required to destroy
    electronic copies of any portions of the Confidential Information created pursuant to standard archival or back-up procedures and not available to end users, and provided that Prospective Purchaser may retain one (1) copy of the Confidential
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    use of the Confidential Information may irreparably injure the Ionis Parties. If any action should have to be brought by Ionis against Prospective Purchaser to enforce the provisions of this Agreement, Prospective Purchaser recognizes, acknowledges and
    agrees that Ionis shall be entitled to seek all of the civil remedies provided by federal, state and local law, including without limitation, preliminary and permanent injunctive relief restraining Prospective Purchaser from any actual or threatened
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    provided that the sender promptly delivers a hard copy to the recipient by the method set forth in (i) or (ii), in each case to the applicable addresses set forth below or to such other address as such Party has designated by notice so given to the
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">San Diego, CA 92121-1909&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-size: 10pt">Attn: David L. Crawford, Esq.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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    refusal to accept delivery), as evidenced by the notifying Party&#8217;s receipt of written or electronic confirmation of such delivery or refusal, and such notice sent electronically in accordance with clause (iii) shall be deemed to have been given upon
    the date that such electronic notification was sent, provided such notice clearly confirms, without alteration of the email, the date and time the email was sent, in each case if such notice is received by the Party to be notified between the hours of
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 35.95pt">&#160;</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">EXHIBIT I</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>TENANT CONSTRUCTION MANUAL</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">[Attached]</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.25in">c)</td>
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  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.25in">d)</td>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">These should include lighting layout.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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      <tr style="vertical-align: top">
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        <td style="width: 0.5in">1.03.03</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">These plans should be appropriately scaled and indicate methods of construction.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="text-align: justify"><b><i>Complete Electrical, Mechanical, Sprinkler, Building Automation, Security, Communications, Data, Life Safety System Drawings (scale: 1/8&#8221;=1&#8217;) complete with Engineer&#8217;s stamp.</i></b></td>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">Details of all alterations and all additions to the <b>BASE BUILDING</b>, as well as base building conditions, which remain unchanged.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">Details of all metering equipment changes to conform to base building standards. Schedule for any changes to fire, sprinkler and security systems.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.75in"></td>
        <td style="width: 0.5in">1.03.06</td>
        <td style="text-align: justify"><b><i>Complete Structural Drawings</i></b></td>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">These drawings must be supplied where special conditions warrant their production i.e. openings in slabs, erection of racking units, the addition of cranes, ramps, etc.</p>
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  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.75in"></td>
        <td style="width: 0.5in">1.03.07</td>
        <td style="text-align: justify"><b><i>Completion</i></b></td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in">Upon completion of construction, to the extent required by the Lease the Tenant is responsible to submit &#8220;as built&#8221; Architectural, Electrical, Mechanical, Security,
    Communications, Data and Structural Drawings on CAD ver. 14 or later disk to the Landlord for their records.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 66.3pt">&#160;</p>
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      <tr style="vertical-align: top">
        <td style="width: 0.5in">1.04</td>
        <td>Certificates and Approvals</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in">The Tenant is responsible for ensuring that all the following requirements have been complied with before construction begins:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in">1.</td>
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  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="text-align: justify"><b><u>Permits</u></b> Tenant&#8217;s design and construction work must comply with all applicable by-laws. The Tenant must obtain all necessary permits and approvals or construction work in the leased premises from the
          appropriate government authorities. Permits and approval that are required to commence construction must be obtained before construction begins within the leased premises. A copy of all permits must be delivered to the Landlord. The Tenant must
          correct immediately any work, which does not meet with the approval of the building inspector, even though the Tenants drawings may have been reviewed previously by the appropriate government authorities and the Landlord.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.5in">4.</td>
        <td style="text-align: justify"><b><u>Workers Compensation</u></b> To the extent applicable, Tenant contractor shall furnish written evidence of good standing with the North Carolina Industrial Commission and that all employees engaged in the work
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      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in">5.</td>
        <td style="text-align: justify"><b><u>Occupational Health and Safety</u></b> The Tenant acknowledges that it is solely responsible for the health and safety of all its employees and workers, as well as for the continuing safe conditions in the
          Premises. The Tenant shall comply with and shall require all of its employees and workers to comply with the provisions of all Laws respecting Occupational Health and Safety, the Environment, Worker&#8217;s Compensation and the safe condition of the
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      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.5in; text-indent: 0">All materials and supplies used by the Tenant&#8217;s personnel in the Demised Premises and the Lands shall be used, handled, stored, otherwise dealt with and properly
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
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        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">3</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -0.05pt">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">1.05</td>
        <td>Appointment of Contractors</td>
      </tr>

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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-indent: 0">All Tenant contractors are subject to approval by the Landlord to the extent provided in the Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">1.06</td>
        <td>Reserved</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">1.07</td>
        <td style="text-align: justify">Commencement of Construction</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-indent: 0; text-align: justify">For work subject to Landlord consent, the Tenant is required to carry out its construction work in strict accordance with the &#8220;Landlord
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -1.1pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.25in; text-indent: 0">Construction may proceed only after the Tenant has:&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.25in">a)</td>
        <td style="text-align: justify">Submitted acceptable evidence of insurance coverage to the Landlord as set out in these Rules and Regulations.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1.5in"></td>
        <td style="width: 0.25in">b)</td>
        <td style="text-align: justify">Posted all required permits and safety signage on site, where applicable.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1.5in"></td>
        <td style="width: 0.25in">c)</td>
        <td style="text-align: justify">For work subject to Landlord&#8217;s consent, made available on the leased premises one (1) set of prints, of the Tenant Design Working Drawings and Specifications for the duration of the construction period for reference
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      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 1.5in"></td>
        <td style="width: 0.25in">d)</td>
        <td style="text-align: justify">For work subject to Landlord&#8217;s consent, submitted a schedule showing the timetable for the progress and completion of the Tenant&#8217;s work and a list of all trades requiring access to the premises including the trades
          address and telephone number.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
        <td style="width: 0.5in">1.08</td>
        <td>Completion of Tenant&#8217;s Construction</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0.05pt">Following completion of the job, and within 30 days, the Tenant must submit to the Landlord a certificate from its architect or designer stating that all
    work, including that of the mechanical and electrical contractors (if any), has been completed substantially in accordance with the reviewed drawings if such work was subject to Landlord&#8217;s consent. Upon the request of Landlord or the property manager,
    Tenant shall provide similar certifications for Minor Alterations previously performed (to the extent not already in the possession of Landlord).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0.05pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: -0.05pt">A full set of architectural, mechanical and electrical &#8220;as built&#8221; CAD drawings ver. 14 or later shall accompany the above noted certificates where required
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
        </td>
        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">4</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -0.05pt">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0">Further, the Landlord requires copies of all permits and certificates issued by authorities having jurisdiction over all or any part of the Tenant&#8217;s Alterations.
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
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        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">5</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: -0.05pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

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      </tr>

  </table>
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      </tr>

  </table>
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      </tr>

  </table>
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  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">&#9632;</font></td>
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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      </tr>

  </table>
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  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">&#9632;</font></td>
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      </tr>

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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; color: #80BD8B">

      <tr style="vertical-align: top">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-indent: 0">It is the tenant&#8217;s responsibility to ensure the construction has been completed in accordance with this Document. The following documents must be complete and
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        <td style="text-align: left; padding-right: 83.6pt">Final Electrical and Mechanical engineers sign-off stating work is completed substantially in accordance with design drawings and specifications.</td>
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      <tr style="vertical-align: top">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
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      <tr style="vertical-align: top">
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        <td style="text-align: left; padding-right: 71.85pt">As-built Mechanical Drawings with the associated CAD disk ver. 14 or later. Disks are to be labeled as follows:</td>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
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      <tr style="vertical-align: top">
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      <tr style="vertical-align: top">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
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      <tr style="vertical-align: top">
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        <td style="text-align: left">Name of Company Prepared By</td>
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="text-align: left; padding-right: 1in">As and to the extent required by the Lease, As-built Electrical Drawings with the associated CAD disk ver. 14 or later. Disks are to be labeled as follows:</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
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      <tr style="vertical-align: top">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
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      <tr style="vertical-align: top">
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        <td style="text-align: left">Name of Company Prepared By</td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">Exhibit A</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b><u>REQUIRED CONTRACTOR AND SUBCONTRACTOR INSURANCE</u></b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">Certificates of Insurance</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Landlord requires all contractors and subcontractors performing work at the Property to carry insurance. Property Management collects certificates of insurance, which contain information
    about the vendor&#8217;s insurance. This insurance must meet certain minimum requirements and name Landlord, Oxford Properties Group, Arcadia Management Group, Inc., and Oxford I Asset Management US as additional insureds.</p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">Service Contractor Certificates</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">The specific insurance requirements for a particular service contractor are those written into their contract with the building owner/manager or tenant, and to the extent approved by
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">The standard operating procedures require having a certificate of insurance naming Landlord, Oxford Properties Group, Arcadia Management Group, Inc., and Oxford I Asset Management US as
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left">General Guidelines</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">The following are insurance guidelines for contractors and subcontractors performing work under $20,000,000; for work in excess of such amount, the limits of liability will be subject to
    Landlord&#8217;s reasonable approval. Landlord and Tenant shall reasonably cooperate in good faith to determine such insurance liability limits within thirty (30) days after the Effective Date.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">1.</td>
        <td style="text-align: justify"><b>Workers Compensation:</b> Statutory Coverage in accordance with the laws of your state.</td>
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  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">2.</td>
        <td style="text-align: justify"><b>Employers Liability:</b> Limits of not less than $1,000,000 each accident/occurrence, $1,000,000 each employee/disease, $1,000,000 disease/policy limit.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">3.</td>
        <td style="text-align: justify">
          <p style="margin-top: 0; margin-bottom: 0"><b>General Liability:</b> Please see the chart below for General Liability per Occurrence/ General Aggregate.</p>
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          <p style="margin-top: 0; margin-bottom: 0">Commercial General Liability, including but not limited to comprehensive form, premises operations, explosion and collapse hazard and underground hazard, products and a minimum of twelve (12) months
            completed operations hazard, contractual liability on a &#8220;blanket&#8221; basis designating all written contracts related to the work, broad form property damage (including completed operations), independent contractors&#8217; protective, personal injury
            liability, automobile liability comprehensive form for owned, hired and non-owned vehicles, elevators and escalators hazards, and incidental medical malpractice coverage hazards, and as follows: combined single limits for (i) bodily injury and
            (ii) property damages, endorsed such that the policy aggregate applies to each property location where work occurs. Bodily injury shall include, without limitation, damages for care and loss of services because of bodily injury, including death
            at any time resulting therefrom, sustained by any person or persons. Property Damage Liability Insurance shall include, without limitation, losses due to damages to or destruction of tangible property, including loss of use of such property
            resulting therefrom in compliance with the amounts set forth above; Contractor shall provide X, C and U coverage if Contractor&#8217;s operations involve any exposure to explosion, collapse or underground damage. Products and Completed Operations to
            be maintained for 3 years after final payment.</p>
        </td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
        </td>
        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">9</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">4.</td>
        <td style="text-align: justify"><b>Automobile Liability:</b> Bodily injury and property damage in an amount not less than $2,000,000 combined single limit covering all owned, non-owned, hired or leased vehicles.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">5.</td>
        <td style="text-align: justify"><b>Excess / Umbrella Liability:</b> $1,000,000 in excess of the above primary Employer&#8217;s Liability, General Liability, and Automobile Liability.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">6.</td>
        <td style="text-align: justify"><b>Property: </b>Property Insurance will cover the physical loss, including theft, or damage to equipment, machinery, supplies or tools owned, leased, hired or borrowed by contractor, utilized or operated by
          contractor while performing contracted services. The valuation basis shall be &#8220;replacement cost&#8221;.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">7.</td>
        <td style="text-align: justify"><b>Professional Liability (Errors and Omissions): </b>If the nature of the work involves a professional liability exposure (e.g. design/build), contractor shall maintain professional liability (errors and omissions)
          coverage at a minimum limit of $2,000,000 or $5,000,000, depending on project size, for each claim.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">8.</td>
        <td style="text-align: justify"><b>Contractors Pollution - Asbestos Legal Liability: </b>If the nature of the services performed involves pollutants or any other materials which would affect soil, water or structures, then the contractor shall
          maintain contractors pollution &#8211; asbestos legal liability coverage for a limit of not less than $1,000,000 each occurrence - $2,000,000 policy aggregate, including errors and omissions. However, see attached requirements for higher limits for
          asbestos abatement and hazardous material removal contractors.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Certificate Holders, Additional Insured&#8217;s, and Additionally Insured Endorsement</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Service contractors are required to add the Landlord as an additional insured with regard to the General Liability policy. An additional Additionally Insured
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">CERTIFICATE OF INSURANCE LIMITS REQUIREMENT</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">1.</td>
        <td style="text-align: justify; padding-right: 90.4pt">For insurance requirements for crane lifts or any special contract work; contact for the property team for specific coverage and language.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt">2.</td>
        <td style="text-align: justify; padding-right: 119.75pt">Commercial General Liability Coverage Required (millions, per occurrence and aggregate) is the sum of the basic coverage + excess umbrella.</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.5in">See Example for Electrical Maintenance below:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif">&#9679;</font></td>
        <td style="text-align: left">Commercial General Liability Coverage Required = 5MM. This requirement is met by:</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif">&#9679;</font></td>
        <td style="text-align: left">General Liability each Occurrence 3MM + Excess umbrella 2MM = 5MM</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 27pt"></td>
        <td style="width: 27pt"><font style="font-family: Times New Roman, Times, Serif">&#9679;</font></td>
        <td style="text-align: left">General Liability General Aggregate 3MM + Excess umbrella 2MM = 5MM</td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
        </td>
        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">10</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">Certificate of Insurance Limits</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 32%; border: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><b>Type of Service</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>General <br>
              Liability <br>
              Each <br>
              Occurrence / <br>
              General</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Aggregate</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Employers&#8217; <br>
              Liability</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Each Accident / <br>
              Disease</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>&#8211; Each Employee</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><b>/ Disease &#8211; Policy</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"><b>Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; text-align: center; margin-bottom: 0pt"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Automobile <br>
              Liability <br>
              Combined <br>
              Single Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Excess / <br>
              Umbrella <br>
              Liability Each <br>
              Occurrence / <br>
              Aggregate</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Alarm Systems Service and Repair</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Appliance Repair &amp; Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Architectural <b>*</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Asbestos Abatement and Hazardous Material Removal <b>****</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
        </td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Audio-Visual Equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Backflow Testing</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM/1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Cabling</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Carpet/Floor Finishes</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Crane/Rigging</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Custom Fabrication &amp; Installation Millwork</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Doors &amp; Locks</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Electrical Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Elevator/Escalator Service &amp; Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Elevator interior installation</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Engineering Consulting Service<b>*</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Fire Extinguishing in Restaurants</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Fitness Equipment Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Garbage Removal &amp; Disposal, incl. dumpster maintained on premises</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">General Contractors</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Generator Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Glass Repair &amp; Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Glass Repair &amp; Maintenance elevated</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
        </td>
        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">11</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 32%; border: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><b>Type of Service</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>General <br>
              Liability <br>
              Each <br>
              Occurrence / <br>
              General</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Aggregate</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Employers&#8217; <br>
              Liability</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Each Accident / <br>
              Disease</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>&#8211; Each Employee</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>/ Disease &#8211; Policy</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Automobile <br>
              Liability <br>
              Combined <br>
              Single Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>Excess / <br>
              Umbrella <br>
              Liability Each <br>
              Occurrence / <br>
              Aggregate</b>&#160;</p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Graffiti Removal</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Handyman</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Heating, Ventilation &amp; Air Conditioning Service/install</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Insulation/Fiberglass</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Interior Design Consulting<b>*</b></font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Life Safety/Fire Equipment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Life Safety/Monitoring</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Lighting re-lamping (interior)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Elevated Lighting Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM /5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Moves/Relocations/ reconfiguration</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Office Equipment Service</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Overhead and Revolving Door</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Painting</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Parking Surface Maintenance/sweeping</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Paving and Striping</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Plumbing</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Power washing (non-elevated)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Power washing (elevated)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM /5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Pump Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Roofing</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM /5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Signage non elevated</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Signage Elevated</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Sprinkler System Service and Repair</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Stonework/Marble/wood/ metal cleaners and refinishers Repair &amp;
            Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">2MM</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.75in; text-align: justify">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="border-collapse: collapse; font: 10pt Times New Roman, Times, Serif; width: 100%">

      <tr style="vertical-align: top; text-align: left">
        <td style="width: 90%"><br>
        </td>
        <td style="width: 10%; text-align: right; vertical-align: bottom"><font style="font-family: Times New Roman, Times, Serif; font-size: 8pt">12</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top; background-color: #FFFFCC">
        <td style="width: 32%; border: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0"><b>Type of Service</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>General <br>
              Liability <br>
              Each <br>
              Occurrence / <br>
              General</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>Aggregate</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>Employers&#8217; <br>
              Liability</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>Each Accident / <br>
              Disease</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>&#8211; Each Employee / <br>
              Disease &#8211; Policy</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0"><b>Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"><b>Automobile <br>
              Liability <br>
              Combined <br>
              Single Limit</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; text-indent: 0"></p>
        </td>
        <td style="width: 17%; border-top: black 1pt solid; border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center; vertical-align: bottom">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><b>Excess / <br>
              Umbrella <br>
              Liability Each <br>
              Occurrence / <br>
              Aggregate</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"></p>
        </td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Telecommunications and TV Equip. Master Wiring and Antennas (non-elevated)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Telecommunications and TV Equip. Master Wiring and Antennas (elevated or
            roof)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">UPS/SEP Equipment Maintenance</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">3MM / 3MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Walk Off Mat Cleaning</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Water Treatment</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 2MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Window coverings (non-elevated)</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM / 1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; border-left: black 1pt solid; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">Window Washing and Swing Station Equipment Services</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">5MM / 5MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; text-align: center; padding-right: 5pt; padding-left: 5pt"><font style="font-size: 10pt">1MM</font></td>
        <td style="border-right: black 1pt solid; border-bottom: black 1pt solid; padding-right: 5pt; padding-left: 5pt; text-align: center"><font style="font-size: 10pt">10MM</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; text-indent: 0in">*<font style="font-family: Times New Roman, Times, Serif">&#160; </font>Design and Engineering vendors must include Professional Errors and Omissions
    Insurance in the following amounts:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left; text-indent: 0in"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">&#9675;</font></td>
        <td style="text-align: left">Architects = 5MM</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">&#9675;</font></td>
        <td style="text-align: left">Engineers = 5MM</td>
      </tr>

  </table>
  <p style="margin: 0pt 0; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif">&#9675;</font></td>
        <td style="text-align: left">Interior Design = 2MM (or call Risk Management if limited scope)</td>
      </tr>

  </table>
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<TYPE>EX-10.26
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<FILENAME>exhibit10-26.htm
<DESCRIPTION>EXHIBIT 10.26
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">LEASE AGREEMENT</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>OCTOBER 20, 2022</b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">2850 2855 &amp; 2859 GAZELLE OWNER (DE) LLC</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><b>a Delaware limited liability company</b></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center">IONIS PHARMACEUTICALS, INC.,<br>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center">BASIC LEASE INFORMATION</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">For convenience of the parties, certain basic provisions of this Lease are set forth herein, and are, together with any Exhibits and Schedules, expressly incorporated
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      <tr style="vertical-align: top">
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><b>TERMS OF LEASE</b></p>
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      <tr style="vertical-align: top">
        <td style="text-align: justify">&#8220;<b>Commencement Date</b>&#8221;:</td>
        <td style="text-align: justify">October 20, 2022 &#160;(i.e., upon the occurrence of &#8220;Closing,&#8221; as such term is defined in that certain Purchase and Sale Agreement dated as of October 20, 2022, (the &#8220;<b>PSA</b>&#8221;) between Tenant, as seller, and Landlord,
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        <td style="text-align: justify">&#160;</td>
        <td style="text-align: justify">&#160;</td>
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        <td style="text-align: justify">&#8220;<b>Premises</b>&#8221;:</td>
        <td style="text-align: justify">That certain real property described on <u>Exhibit A</u> attached hereto and the buildings (the &#8220;<b>Buildings</b>&#8221;) and other improvements thereon, located at 2850, 2855 &amp; 2859 Gazelle Court, Carlsbad, 92010
          California consisting of approximately 246,699 gross square feet, and the appurtenances thereto. The square footage of the Premises set forth above is deemed conclusive and shall not be subject to remeasurement.</td>
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      <tr style="vertical-align: top">
        <td style="text-align: justify">&#160;</td>
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        <td style="text-align: justify"><b>&#8220;Companion Lease&#8221;:</b></td>
        <td style="text-align: justify">That certain lease to be executed between Landlord or its affiliate and Tenant pursuant to the PSA for certain real property located across Whiptail Loop W adjacent to the Premises (the &#8220;<b>Companion Premises</b>&#8221;)
          and the improvements to be constructed thereon consisting of approximately 164,833 square feet, and the and the improvements thereon appurtenances thereto, as described therein. </td>
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      <tr style="vertical-align: top">
        <td style="text-align: justify">&#160;</td>
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        <td style="text-align: justify">&#8220;<b>Term</b>&#8221;: (<u>Article 1</u>)</td>
        <td style="text-align: justify">The period commencing on the Commencement Date and ending on the Expiration Date. </td>
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        <td style="text-align: justify"><b>&#8220;Expiration Date</b>&#8221;</td>
        <td style="text-align: justify">The date that is one hundred eighty (180) months after the Commencement Date; provided, however, if Landlord, or its affiliate, and Tenant enter into the Companion Lease, the Expiration Date of this Lease shall be
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        <td style="text-align: justify; width: 38%">&#8220;<b>Escalation</b>&#8221;: (<u>Article 2</u>)</td>
        <td style="text-align: justify; width: 62%">The percentage of increase, if any, shown by the Consumer Price Index for All Urban Consumers U.S. City Average, All Items (base years 1982-1984 = 100) (&#8220;<b>Index</b>&#8221;), published by the United States
          Department of Labor, Bureau of Labor Statistics, for the month immediately preceding the Adjustment Date as compared with the Index for the month immediately preceding the Commencement Date (with respect to the first Adjustment Date), or the
          month immediately preceding the prior Adjustment Date (for all subsequent Adjustment Dates), but the percentage of increase shall not be less than 2.5% nor greater than 5.5%. </td>
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        <td style="text-align: justify">&#8220;<b>Option to Renew</b>&#8221;: (<u>Article 1</u>)</td>
        <td style="text-align: justify">Tenant shall have two (2), five year (5) options at ninety-five percent (95%) of fair market rent.</td>
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        <td style="text-align: justify">&#8220;<b>Base Rent</b>&#8221;: (<u>Article 2</u>)</td>
        <td style="text-align: justify">An annual amount of $15,542,037 beginning on the Commencement Date until the first Adjustment Date, and thereafter the amount calculated pursuant to Section 2.1.3. </td>
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        <td style="text-align: justify">&#8220;<b>Net Lease</b>&#8221;: (<u>Article 2</u>)</td>
        <td style="text-align: justify">Landlord and Tenant acknowledge and agree that this is an &#8220;absolute net lease&#8221; and that Landlord shall receive the Base Rent during the Term, free from all charges, assessments, impositions, expenses and deductions
          of any and every kind or nature whatsoever relating to the Premises.&#160;&#160;Landlord shall have no obligations relating to the repair, maintenance or operation of the Premises, or any part thereof&#8204;. Tenant shall be solely responsible for same.</td>
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        <td style="text-align: justify">&#160;</td>
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        <td>&#8220;<b>Purchase Option</b>&#8221;: (Article 11)</td>
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        <td>&#8220;<b>Security Deposit/Letter of Credit</b>&#8221;: (<u>Article 2</u>)</td>
        <td style="text-align: justify">Tenant shall provide a Letter of Credit equal to three (3) months of the initial Base Rent at Closing.</td>
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        <td>&#160;</td>
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        <td>&#8220;<b>Permitted Use</b>&#8221;: (<u>Article 3</u>)</td>
        <td style="text-align: justify">Premises may be used solely for biotechnology and other life sciences uses, including research and development, laboratory, manufacturing, assembly, storage, warehousing, office and administrative uses, all of which
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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      <tr style="vertical-align: top">
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
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        <td style="width: 38%">&#8220;<b>Address of Tenant</b>&#8221;: (<u>Article 13</u>)</td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Ionis Pharmaceuticals, Inc.<br>
            2855 Gazelle Ct.<br>
            Attention: General Counsel<br>
            Email: [***]</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 7pt 0pt 0; text-align: justify">With a copy to:</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Cooley LLP</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">4401 Eastgate Mall</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">San Diego, CA&#160;&#160; 92121-1909</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Attn: David L. Crawford, Esq.</p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Email: [***]</p>
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        <td>&#8220;<b>Address of Landlord</b>&#8221;: (<u>Article 13</u>)&#160;&#160;</td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">c/o Oxford Property Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">125 Summer Street, 12<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Boston, MA 02110</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">United States</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Attn: Kristin Binck, Esq.,</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Vice President, Legal</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Email: [***]</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">With a copy to:</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">c/o Oxford Property Group</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">101 Second St, Suite 300</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">San Francisco, CA 94105</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Attn: Abby Mondani</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">and</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">DLA Piper LLP (US)</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">33 Arch Street, 26<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> floor</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Boston, MA 02110</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">United States</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Attn: John L. Sullivan, Esq.</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">Email: [***]</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
        </td>
      </tr>

  </table>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">3</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 38%">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><b>TERMS OF LEASE</b></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">&#160;</p>
        </td>
        <td style="text-align: justify; width: 62%"><b>DESCRIPTION</b></td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; width: 100%; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 38%"></td>
        <td style="width: 62%">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">and all legal notices shall also be sent to:&#160;</p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify">[***]&#160;</p>
        </td>
      </tr>

  </table>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">4</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center"><u>TABLE OF CONTENTS</u></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%">

      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 1&#160; LEASE OF PREMISES; TERM</td>
        <td style="text-align: right">1</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="width: 8%; padding-left: 0.375in;">1.1&#160;&#160;</td>
        <td style="width: 85%;">Lease</td>
        <td style="text-align: right; width: 5%">1</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">1.2&#160;&#160;&#160;</td>
        <td>As Is; No Representations</td>
        <td style="text-align: right">1</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">1.3&#160;&#160;</td>
        <td>Holdover</td>
        <td style="text-align: right">2</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">1.4&#160;&#160;</td>
        <td>Extension Option</td>
        <td style="text-align: right">2</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 2&#160; RENT</td>
        <td style="text-align: right">4</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">2.1&#160;</td>
        <td>Base Rent and Additional Rent</td>
        <td style="text-align: right">4</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">2.2&#160;</td>
        <td>Expenses; Taxes; Insurance Expenses</td>
        <td style="text-align: right">5</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">2.3&#160;</td>
        <td>Net Lease</td>
        <td style="text-align: right">8</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">2.4&#160;&#160;</td>
        <td>Interest and Late Charge</td>
        <td style="text-align: right">9</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">2.5&#160;</td>
        <td>Security Deposit</td>
        <td style="text-align: right">9</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 3&#160; USE, COMPLIANCE WITH LAWS, HAZARDOUS MATERIALS, DOGS</td>
        <td style="text-align: right">12</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.1&#160;</td>
        <td>Use</td>
        <td style="text-align: right">12</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.2&#160;</td>
        <td>Compliance with Applicable Laws</td>
        <td style="text-align: right">12</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.3&#160;</td>
        <td>Hazardous Materials</td>
        <td style="text-align: right">13</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.4&#160;&#160;</td>
        <td>Alterations</td>
        <td style="text-align: right">18</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.5&#160;&#160;</td>
        <td>Jeopardy of Insurance</td>
        <td style="text-align: right">21</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.6&#160;&#160;&#160;</td>
        <td>Dogs</td>
        <td style="text-align: right">21</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">3.7&#160;&#160;</td>
        <td>LEED Standards</td>
        <td style="text-align: right">22</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 4&#160; REPAIR AND MAINTENANCE; SERVICES</td>
        <td style="text-align: right">23</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">4.1&#160;&#160;</td>
        <td>Tenant Repair and Maintenance Obligations</td>
        <td style="text-align: right">23</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">4.2&#160;&#160;</td>
        <td>Condition of Premises on Surrender</td>
        <td style="text-align: right">23</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">4.3&#160;</td>
        <td>Services</td>
        <td style="text-align: right">24</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 5 &#160;ASSIGNMENT AND SUBLETTING</td>
        <td style="text-align: right">25</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">5.1&#160;&#160;</td>
        <td>General Prohibition on Transfers</td>
        <td style="text-align: right">25</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">5.2&#160;&#160;</td>
        <td>Other Permitted Transfers</td>
        <td style="text-align: right">27</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">5.3&#160;&#160;</td>
        <td>Non-Transfers</td>
        <td style="text-align: right">28</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">5.4&#160;&#160;</td>
        <td>Conditions to Effectiveness</td>
        <td style="text-align: right">28</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">5.5&#160;&#160;</td>
        <td>Miscellaneous</td>
        <td style="text-align: right">28</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>

  </table>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">5</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%">

      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 6 &#160;INDEMNIFICATION; rELEASE; INSURANCE</td>
        <td style="text-align: right">30</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in; width: 8%;">6.1&#160;&#160;&#160;</td>
        <td style="width: 85%;">Indemnification and Release</td>
        <td style="text-align: right; width: 5%">30</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">6.2&#160;&#160;&#160;</td>
        <td>Insurance</td>
        <td style="text-align: right">31</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 7&#160; THIRD PARTIES</td>
        <td style="text-align: right">33</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">7.1&#160;&#160;</td>
        <td>Subordination, Attornment and Non-Disturbance</td>
        <td style="text-align: right">33</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">7.2&#160;&#160;</td>
        <td>Mortgagee&#8217;s Right to Cure</td>
        <td style="text-align: right">34</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">7.3&#160;</td>
        <td>Sale of the Premises</td>
        <td style="text-align: right">35</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">7.4&#160;&#160;</td>
        <td>Estoppel Certificates</td>
        <td style="text-align: right">35</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">7.5&#160;&#160;</td>
        <td>Liens</td>
        <td style="text-align: right">35</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">Article 8&#160; EVENTS OF DEFAULT &amp; REMEDIES</td>
        <td style="text-align: right">36</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif; text-transform: uppercase">
        <td colspan="2">&#160;</td>
        <td style="text-align: right">&#160;</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">8.1&#160;&#160;</td>
        <td>Events of Default</td>
        <td style="text-align: right">36</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">8.2&#160;&#160;</td>
        <td>Remedies</td>
        <td style="text-align: right">37</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">8.3&#160;&#160;</td>
        <td>Landlord Default</td>
        <td style="text-align: right">41</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td style="padding-left: 0.375in;">8.4&#160;&#160;</td>
        <td>Non-Waiver</td>
        <td style="text-align: right">41</td>
      </tr>
      <tr style="text-align: left; vertical-align: bottom; font: 10pt Times New Roman, Times, Serif">
        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
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        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
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        <td style="text-align: right">51</td>
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        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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        <td style="padding-left: 0.375in;">11.5&#160;&#160;&#160;</td>
        <td>Confidentiality</td>
        <td style="text-align: right">55</td>
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        <td>&#160;</td>
        <td>&#160;</td>
        <td style="text-align: right">&#160;</td>
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        <td style="text-align: right">55</td>
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        <td>Assignment of Rents</td>
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      <tr style="vertical-align: top">
        <td style="width: 10%">Exhibit A</td>
        <td style="width: 90%">Legal Description of the Premises</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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        <td>[RESERVED]</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit C</td>
        <td>Form of Tenant Estoppel Certificate</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit D</td>
        <td>Form of Memorandum of Lease</td>
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        <td>&#160;</td>
        <td>&#160;</td>
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        <td>Exhibit E</td>
        <td>Form of SNDA</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td>Exhibit F</td>
        <td>Form of Non-Disclosure and Confidentiality Agreement</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit G</td>
        <td>Landlord Signage</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit H</td>
        <td>Plans and Specifications for Conference Center Alterations</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit I</td>
        <td>Tenant Immediate and Short Term Repairs</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit J</td>
        <td>Commencement and Termination Date Agreement</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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        <td>Exhibit K</td>
        <td>Tenant Construction Manual</td>
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      <tr style="vertical-align: top">
        <td>&#160;</td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
        <td>Exhibit L</td>
        <td>Tenant Standard Operating Procedures</td>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-family: 'Times New Roman', Times, serif; font-size: 8pt; color: #000000; font-weight: normal; font-style: normal;">7</font></div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">This Lease Agreement (this &#8220;<b>Lease</b>&#8221;),


      dated ____________, 2022 (the &#8220;<b>Effective Date</b>&#8221;), is made between 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC, a Delaware limited liability company (&#8220;<b>Landlord</b>&#8221;), and Ionis Pharmaceuticals, Inc., a Delaware corporation (&#8220;<b>Tenant</b>&#8221;).</font></p>
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  <p style="font: bold 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article
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      Landlord hereby leases to Tenant, and Tenant hereby leases from Landlord, the Premises for the Term. Landlord and Tenant acknowledge that Tenant is in possession of the Premises as of the Commencement Date and accepts the Premises in its &#8220;as is&#8221;
      condition with all faults. All of the terms and covenants of this Lease shall be effective as of the Effective Date. After the Commencement Date, Tenant and Landlord shall execute, acknowledge and deliver a written agreement in the form attached
      hereto as <u>Exhibit J</u> memorializing the Commencement Date, the Expiration Date, the original Term, and the commencement and termination dates of the Extension Terms if such are exercised.</font></p>
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      (including, without limitation, any utilities serving the Premises, any structural components of the improvements or the condition of any Building system), (b) the restrictions that may affect the conduct of Tenant&#8217;s business in, or Tenant&#8217;s use of,
      the Premises, or any other rights or benefits under this Lease, (c) the suitability of the Premises for Tenant&#8217;s intended Permitted Use, or (d) compliance with Environmental Laws at the Premises or any environmental conditions at, or Hazardous
      Materials on, under, above, emanating to or from, or having emanated to or from, the Premises. TENANT EXPRESSLY WAIVES ANY WARRANTY OF CONDITION OR OF HABITABILITY OR SUITABILITY FOR OCCUPANCY, USE, HABITATION, FITNESS FOR A PARTICULAR PURPOSE OR
      MERCHANTABILITY, EXPRESS OR IMPLIED, RELATING TO THE PREMISES. Tenant assumes full responsibility for all costs and expenses required to cause the Premises to comply with all Applicable Laws. &#8220;<b>Applicable Laws</b>&#8221; means all applicable present and
      future federal, state, municipal and local laws, codes, ordinances, rules and regulations of governmental authorities, committees, associations, or other regulatory committees, agencies or governing bodies having jurisdiction over the Premises or any
      portion thereof, Landlord or Tenant, including both statutory and common law and Environmental Laws. &#8220;<b>Environmental Laws</b>&#8221; means any applicable present and future federal, state and local laws, statutes, ordinances, rules, and regulations, as
      well as common law, relating to protection of human health, natural resources or the environment or governing the use, transport, or disposal of biological, bio-hazardous wastes, or radiological elements. The term &#8220;Environmental Laws&#8221; includes, but
      is not limited to, the Comprehensive Environmental Response, Compensation and Liability Act of 1980, as amended (&#8220;<b>CERCLA</b>&#8221;), 42 U.S.C. &#167;9601 et seq.; the Toxic Substance Control Act, 15 U.S.C. &#167;2601 et seq.; the Hazardous Materials
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      et seq.; Federal Water Pollution Control Act, 33 U.S.C. &#167;&#167; 1251 et seq.; Clean Air Act, 42 U.S.C. &#167;&#167; 7401 et seq.; Emergency Planning and Community Right-To-Know Act, 42 U.S.C. &#167;&#167; 11001 et seq.; Occupational Safety and Health Act, 29 U.S.C. &#167;&#167; 65 et
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      otherwise relate to human health, natural resources or the environment, in each case together with their implementing regulations, guidelines, rules, or orders, and all state, regional, county, municipal, and other local laws, regulations,
      ordinances, rules, and orders that are equivalent or similar to the federal and state laws recited above.</font>&#160;</p>
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      and Tenant shall (a) be a tenant at sufferance only, (b) be liable to perform all of the obligations of Tenant set forth in this Lease, and (c) (i) for the first ninety (90) days following the Termination Date, pay Base Rent at a rate of one hundred
      twenty-five percent (125%) of the monthly Base Rent in effect immediately prior to the Termination Date, and (ii) for each month thereafter, pay Base Rent at a rate of one hundred fifty percent (150%) of the monthly Base Rent in effect immediately
      prior to the Termination Date, prorated on a daily basis. If Tenant retains possession of any portion of the Premises for more than thirty (30) days following the Termination Date without Landlord&#8217;s written consent, Tenant shall also pay to Landlord
      all damages, direct, consequential, or indirect, sustained by Landlord by reason of any such holding over. Otherwise, such holding over shall be on the terms and conditions set forth in this Lease as far as applicable. &#8220;<b>Termination Date</b>&#8221; means
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  <p style="margin-top: 0; margin-bottom: 0">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4</font></td>
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      </tr>

  </table>
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      under this Lease immediately prior to the Extension Period, except that Base Rent shall be determined as set forth below and Tenant shall have no further right to extend the Term of this Lease after the end of the second (2<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">nd</sup>) Extension Period; provided, however, it shall be a condition of Tenant&#8217;s exercise of the Extension Option that Tenant also exercise the corresponding &#8220;Extension Option&#8221; as defined in the
      Companion Lease. If Tenant exercises an Extension Option, such extension shall apply to the entire Premises. Tenant may exercise an Extension Option only by giving Landlord irrevocable and unconditional written notice thereof (the &#8220;<b>Extension
        Notice</b>&#8221;) on or before the date which is twelve (12) months prior to the commencement date of each applicable Extension Period and such Extension Period shall commence on the day immediately succeeding the expiration date of the preceding Term
      or the preceding Extension Period, as the case may be, and shall end at midnight Eastern Time on the last day of the applicable Extension Period. Such exercise shall, at Landlord&#8217;s election, be null and void if any Event of Default shall have
      occurred and is continuing at the date of such notice. Upon delivery of the Extension Notice, Tenant shall be irrevocably bound to lease the Premises for the Extension Period. If Tenant shall fail to timely exercise the Extension Option in accordance
      with the provisions of this <u>Section 1.4</u>, then the Extension Option shall terminate, and shall be null and void and of no further force and effect. If this Lease or Tenant&#8217;s right to possession of the Premises shall terminate in any manner
      whatsoever before Tenant shall exercise the Extension Option, then immediately upon such termination the Extension Option shall simultaneously terminate and become null and void. Time is of the essence with regard to this <u>Section 1.4</u>.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Base Rent
        Determination</u>. The Base Rent starting on the Commencement Date of each Extension Period and continuing for sixty (60) months thereafter will be ninety-five percent (95%) of the then-prevailing market rate for new leases for comparable life
      sciences office and lab space to the Premises in comparable buildings to the Buildings in the Market Area (defined below) that a willing, comparable, non-equity tenant (excluding sublease and assignment transactions) would pay, and a willing,
      comparable landlord would accept, at arm&#8217;s length, for a similar life sciences laboratory and research space in a first-class or &#8220;Class A&#8221; property (&#8220;<u>Fair Market Rent</u>&#8221;); provided, however, in no event shall the Fair Market Rent rate per month
      for the first year of each Extension Period be less than 103% of the Base Rent rate for the last month of the immediately preceding portion of the Term. Thereafter, escalations in the Base Rent shall be established using standard market escalations
      in the determination of Fair Market Rent, but in no event shall escalations in Base Rent be increased by less than three percent (3%) on each annual anniversary of the Commencement Date of the Extension Term. Fair Market Rent will reflect all
      monetary and non-monetary considerations and other relevant factors taken into account for comparable transactions, including, without limitation, the location of the Premises, age, quality and layout of the existing improvements in the Premises,
      brokerage commissions, improvements paid for by tenant improvement allowances, moving allowances, and all other relevant tenant concessions. Fair Market Rent will be adjusted to take into account the size of the Premises, the length of the Extension
      Period, and the credit of Tenant. The term &#8220;<b>Market Area</b>&#8221; means the real estate market area that includes Carlsbad, Sorrento Valley, Sorrento Mesa, University Town Center, and Delmar Heights.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Fair Market Rent</u>.
      Landlord will notify Tenant of its determination of the Fair Market Rent (consistent with the methodology reflected above) for the applicable Extension Period no later than ninety (90) days prior to the commencement date of the applicable Extension
      Period. If Tenant delivers written notice to Landlord within ten (10) business days after its receipt of Landlord&#8217;s determination of Fair Market Rent whereby Tenant disagrees with Landlord&#8217;s determination of the Fair Market Rent, Tenant shall include
      in its notice Tenant&#8217;s determination of the Fair Market Rent, and Landlord and Tenant will diligently and in good-faith confer for a period of thirty (30) days thereafter (the &#8220;<b>Negotiation Period</b>&#8221;) in an attempt to agree on the Fair Market
      Rent. If Landlord and Tenant are unable to agree on the Fair Market Rent during the Negotiation Period, then, within five (5) business days after the expiration of such period, Landlord and Tenant shall jointly appoint an independent arbitrator (the
      &#8220;<b>Arbitrator</b>&#8221;) who shall not have previously been employed by or otherwise worked with either Landlord or Tenant with experience in real estate activities, including at least ten (10) years&#8217; experience serving as a broker, appraiser and/or
      attorney in leasing transactions involving commercial life sciences laboratory and research space of comparable size and Class A quality to the Premises (collectively, the &#8220;Qualifications&#8221;), which Arbitrator shall, within twenty (20) days following
      the Arbitrator&#8217;s appointment, determine and report in writing to Landlord and Tenant the by selecting either Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent for the Extension Period, according to whichever of the applicable
      determinations is closer to the Fair Market Rent, as determined by the Arbitrator. If Landlord and Tenant cannot agree on the Arbitrator in accordance with the foregoing, Landlord or Tenant may apply to the American Arbitration Association to appoint
      the Arbitrator in accordance with the aforementioned criteria. The Arbitrator shall have no discretion other than to select Landlord&#8217;s or Tenant&#8217;s determination of the Fair Market Rent as aforesaid. The costs of the Arbitrator shall be shared equally
      by Landlord and Tenant, and each of Landlord and Tenant shall reasonably cooperate with the Arbitrator in providing documentation and any other reasonable evidence regarding how Landlord or Tenant, as applicable, arrived at its determination of the
      Fair Market Rent. If the Renewal Period commences prior to the final determination of the Fair Market Rent, Tenant shall pay to Landlord the monthly rate in effect immediately prior to the commencement of the applicable Renewal Period, subject to
      adjustment upon resolution of such dispute.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.4.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>General</u>.
      Notwithstanding any provision of this Section to the contrary, the Extension Option shall be void, at Landlord&#8217;s election, if (i) Tenant is in default hereunder, after any applicable notice and cure periods have expired, at the time Tenant elects to
      extend the Term or at the time the Term would expire but for such extension, or (ii) any Transfer has occurred under Article 5 of the Lease (other than a Permitted Transfer, or a sublease(s) comprising less than twenty-five percent (25%) of the
      Premises).</font></p>
  <p style="font: bold 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in">&#160;</p>
  <p style="font: bold 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article
      2<br>
      RENT</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Base Rent and Additional Rent</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant shall pay to
      Landlord, without notice or demand and without deduction or set-off of any amount for any reason whatsoever, the annual Base Rent in equal monthly payments on or before the first day of each full calendar month during the Term. Base Rent as well as
      any other amounts payable by Tenant to Landlord under the terms of this Lease shall be paid by wire or electronic transfer of funds pursuant to directions provided to Tenant by Landlord. In addition to Base Rent, Tenant shall pay to Landlord a
      property management fee (&#8220;<b>Management Fee</b>&#8221;) of one percent 1%) of the gross annual revenue form the Premises, which amount shall be paid in equal monthly payments on the same date and in the same manner as Base Rent.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; If the Commencement Date
      is not the first day of a calendar month, Tenant shall pay to Landlord on the Commencement Date the prorated Base Rent for period from the Commencement Date until the end of the calendar month in which the Commencement Date occurs. Base Rent due for
      any partial calendar month at the end of the Term shall also be prorated and paid on the first day of such calendar month. Tenant shall pay to Landlord all items of Rent (as defined below), without deduction or offset and without notice or demand
      (except as specifically provided in this Lease in respect of Additional Rent (as defined below)), and Tenant shall deliver such payments to the payment address set forth in the Basic Lease Information, or to such other person, at such other place, or
      in such other manner as Landlord may designate by giving to Tenant Notice (as defined below) thereof. &#8220;<b>Additional Rent</b>&#8221; means all other amounts payable by Tenant to Landlord in accordance with this Lease, other than Base Rent. &#8220;<b>Rent</b>&#8221;
      means all amounts payable by Tenant to Landlord in accordance with this Lease, including, but not limited to Base Rent and Additional Rent.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; Landlord shall, on or
      within thirty (30) days prior to each Adjustment Date, calculate the Escalation after the United States Department of Labor publishes the Index on which the amount of the increase will be based. Landlord&#8217;s determination of the Escalation shall be
      binding absent manifest error. Landlord shall give written notice of the Escalation, multiplied by the number of installments of rent due under this Lease since the Adjustment Date. Tenant shall pay this amount, together with the monthly rent next
      becoming due under this Lease, and shall thereafter pay the monthly rent due under this Lease at this increased rate, which shall constitute Base Rent. Landlord&#8217;s failure to make the required calculations promptly shall not be considered a waiver of
      Landlord&#8217;s rights to adjust the monthly Base Rent due, nor shall it affect Tenant&#8217;s obligations to pay the increased Base Rent, subject to this Section 2.1.3. If Landlord does not deliver its calculation of the Escalation within twelve (12) months
      after the applicable Adjustment Date, Tenant may provide Landlord with a written request for the calculation of the Escalation, and, if Landlord fails to provide the calculation of Escalation (which request shall include, in bold and prominent print
      on the first page, a notation that &#8220;<b>FAILURE TO RESPOND TO THIS REQUEST WITHIN 30 DAYS MAY RESULT IN THE LOSS OF RIGHTS PURSUANT TO SECTION 2.1.3 OF THE LEASE</b>&#8221;) within thirty (30) days after Tenant&#8217;s written request, Tenant shall not be
      required to so pay the increased Base Rent in arrearage for the applicable period based on an Escalation; provided, however, the foregoing waiver of Tenant&#8217;s obligation to pay arrearage amounts for the applicable period shall not affect Landlord&#8217;s
      calculation of any future Escalations. If the Index is changed so that the base year differs from that in effect on the Commencement Date, the Index shall be converted in accordance with the conversion factor published by the United States Department
      of Labor, Bureau of Labor Statistics. If the Index is discontinued or revised during the Term, the government index or computation with which it is replaced shall be used to obtain substantially the same result as if the Index had not been
      discontinued or revised. The &#8220;<b>Adjustment Date</b>&#8221; means the first anniversary of the Commencement Date and on each successive anniversary thereafter during the Term, including any exercised Extension Period.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Expenses; Taxes; Insurance Expenses</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Expenses</u>. Tenant
      shall perform all obligations with respect to the maintenance, operation, repair and replacement of the Premises and shall pay directly for all costs and expenses incurred in connection therewith, including, but not limited to: all insurance,
      maintenance, repair and replacement of any improvements (including, without limitation, the Buildings, the structural and nonstructural components of the Buildings, the Building systems, equipment (owned and maintained), the foundation, roof, walls,
      heating, ventilation, air conditioning, plumbing, electrical, mechanical, utility (owned and maintained) and safety systems, paving and parking areas, roads and driveways); maintenance of exterior areas such as gardening and landscaping, snow removal
      and signage; maintenance and repair of roof membrane, flashings, gutters, downspouts, roof drains, skylights and waterproofing; painting; lighting; cleaning; refuse removal; security; utilities for, or the maintenance of, outside areas; Premises
      personnel costs; rentals or lease payments paid by Tenant for rented or leased personal property used in the operation or maintenance of the Premises; and fees for required licenses and permits, including in order to operate for the Permitted Use. In
      addition to the foregoing, Tenant shall perform the work described in <u>Exhibit I</u>, at Tenant&#8217;s sole cost and expense, within the following time periods: (i) items identified as a Repair Type &#8220;Immediate&#8221; on <u>Exhibit I</u> shall be completed
      within six (6) months after the Commencement Date and (ii) items identified as a Repair Type &#8220;Short Term&#8221; on <u>Exhibit I </u>shall be completed within twelve (12) months after the Commencement Date (with &#8220;replacement reserve items&#8221; to be monitored
      and addressed as noted).</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Taxes</u>. Subject to
      Tenant&#8217;s right to contest Taxes as set forth below, Tenant will pay directly all Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable. Landlord and Tenant shall cooperate to place all Taxes in the
      name of Tenant, however, if and to the extent any Taxes are billed to Landlord, then Tenant shall pay the same upon receipt of such bill from Landlord and provide Landlord with evidence of such payment promptly thereafter. In any event, Tenant shall
      pay all Taxes prior to the date due. &#8220;<b>Taxes</b>&#8221; means all real property taxes and other assessments on the Premises, including, but not limited to, real estate taxes, personal property taxes, transfer taxes, documentary stamps or taxes, fees,
      assessments and other charges of any kind or nature, whether general, special, ordinary, or extraordinary (without regard to any different fiscal year used by such governmental authority) that are levied in respect of this Lease or the Premises (or
      Landlord&#8217;s interest therein), or in respect of any improvement, fixture, equipment, or other property of Landlord, real or personal, located at the Premises, and used in connection with operation of the Premises. Tenant and Landlord acknowledge that
      Proposition 13 was adopted by the voters of the State of California in the June 1978 election (&#8220;<b>Proposition 13</b>&#8221;) and that assessments, taxes, fees, levies and charges may be imposed by governmental agencies for such services as fire
      protection, street, sidewalk and road maintenance, refuse removal and for other governmental services formerly provided without charge to property owners or occupants, and, in further recognition of the decrease in the level and quality of
      governmental services and amenities as a result of Proposition 13, Taxes shall also include any governmental or private assessments or contribution towards a governmental or private cost-sharing agreement charged to the Premises for the purpose of
      augmenting or improving the quality of services and amenities normally provided by governmental agencies. Taxes shall not include (i) Landlord&#8217;s corporate franchise taxes, estate taxes, inheritance taxes or net income taxes, or (ii) transfer taxes or
      other taxes incurred in connection with Landlord&#8217;s sale of the Premises or any interest therein, other than taxes resulting from Proposition 13 reassessment. Tenant shall furnish to Landlord, within thirty (30) days after the last day when any Tax
      must be paid by Tenant as provided in this Section 2.2.2, official receipt of the appropriate taxing authority or other proof satisfactory to Landlord, evidencing the payment thereof. Tenant shall have the right, at Tenant&#8217;s sole cost and upon
      reasonable prior notice to Landlord, to initiate and prosecute any proceeding for the purpose of contesting the assessed valuation of the Premises or any personal property for tax purposes in good faith; provided, that this right to contest shall not
      be deemed or construed to relieve, modify or extend Tenant&#8217;s obligation to pay any Taxes allocable to the Term in a timely manner and prior to when the same shall become due and payable and that prior to any such contest, Tenant (a) pays the Tax
      under protest, (b) obtains and maintains a stay of all proceedings for enforcement and collection by posting a bond or other security required by law, or (c) if Tenant lawfully withholds payments of any contested amounts of Taxes during the contest,
      Tenant has or establishes unrestricted cash reserves to be held by Landlord in an amount equal to 125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contest; provided,
      however, that Landlord shall (1) promptly release such reserve upon resolution of such contest, and/or (2) use such reserve to pay Taxes directly to the applicable taxing authority following resolution of such contest. Tenant shall provide Landlord
      with all notices received or sent to the taxing authorities, as well as regular updates relating to any such contest and afford Landlord an opportunity to participate in all such proceedings. Tenant shall indemnify and defend Landlord and save
      Landlord harmless from all losses, judgments, costs (including without limitation, attorneys&#8217; fees), liabilities and expenses incurred in connection with such proceedings and shall, promptly after the final determination of such contest, fully pay
      and discharge the amounts which shall be levied, assessed, charged or imposed or be determined to be payable therein or in connection therewith, together with all penalties, fines, costs and expenses thereof or in connection therewith). Landlord
      shall have the right to (a) contest or dispute any Taxes (or file an appeal related thereto), without Tenant&#8217;s prior written consent, at Landlord&#8217;s sole cost and expense, or (b) request that Tenant contest or dispute such Taxes (or file an appeal
      related thereto), in which event, Tenant, in Tenant&#8217;s sole discretion, may agree to contest or dispute such Taxes, at Tenant&#8217;s sole cost and expense. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord,
      Landlord, at its option, may require Tenant to make monthly estimated payments to Landlord on account of Taxes. The monthly payments shall be one twelfth (1/12th) of the amount of Taxes due for the applicable year as reasonably estimated by Landlord
      and shall be payable as Additional Rent on or before the first day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. So long as no Event of Default is then continuing,
      any amounts received by Landlord pursuant to the immediately preceding sentence shall be disbursed to Tenant by Landlord for payment to the applicable taxing authority (or paid to the applicable taxing authority directly by Landlord) when directed by
      Tenant, accompanied by evidence of the amount due. Upon Tenant&#8217;s request, Landlord shall provide Tenant with evidence of any such payments of Taxes made directly by Landlord.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">6</font></div>
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  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Landlord&#8217;s Insurance</u>.
      Tenant shall reimburse or, at Landlord&#8217;s request, pay directly, all premiums, deductibles, and other costs incurred by Landlord in connection with obtaining and maintaining the insurance coverage described in <u>Section 6.2.1</u> below
      (collectively, the &#8220;<b>Insurance Expenses</b>&#8221;). Tenant shall pay the Insurance Expenses no later than fifteen (15) days after demand. If an Event of Default occurs or if otherwise required by any Mortgagee or lender of Landlord, Landlord, at its
      option, may require Tenant to make monthly estimated payments to Landlord on account of Insurance Expenses. The monthly payments shall be one twelfth (1/12th) of the amount of Insurance Expenses due for the applicable year as reasonably estimated by
      Landlord and shall be payable as Additional Rent on or before the first day of each month during the Term, in advance; provided, that, Landlord shall have the right to revise such estimates from time to time. If Landlord requires monthly payments of
      the Insurance Expenses, Landlord will use reasonable efforts to provide a statement reconciling such payments within ninety (90) days after the end of each calendar year, and any underpayments shall paid by Tenant within fifteen (15) days after
      Tenant&#8217;s receipt of the statement, and any overpayments shall be credited to the next payment of Rent that becomes due under the Lease.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">7</font></div>
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.3</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Net Lease.</u></font></td>
      </tr>

  </table>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Absolute Triple Net
        Lease</u>. It is intended by the parties that this Lease be an absolute &#8220;triple net lease,&#8221; imposing upon Tenant the obligation to pay all charges of every kind and nature in connection with the use, operation, management, maintenance, repair, and
      occupancy of the Premises, whether or not recited herein and whether foreseeable or unforeseeable, including, but not limited to, utilities, fees, costs, real estate taxes, sales and use taxes, all operation, management, maintenance and repair costs
      associated with the Premises and the improvements located thereon and costs of compliance with Environmental Laws, except as expressly provided in this Lease. Tenant shall pay to Landlord, net throughout the Term, the Rent due hereunder free of any
      offset, abatement, or other deduction whatsoever, without notice or demand. Except to the extent due to the gross negligence or willful misconduct of, or breach of contract by, Landlord or any of Landlord&#8217;s assignees, agents, servants, employees,
      invitees and contractors (or any of Landlord&#8217;s assignees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Landlord Parties</b>&#8221;; any of them, a &#8220;<b>Landlord Party</b>&#8221;), Tenant assumes the sole responsibility for
      the condition, use, operation, maintenance, management and compliance with Environmental Laws of the Premises, and Landlord shall have no responsibility in respect thereof and shall have no liability for damage to Tenant&#8217;s personalty on any account
      or for any reason whatsoever. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant shall not be required to pay, or reimburse Landlord for: (i) depreciation charges, penalties, premiums, interest and principal payments on
      mortgages and other debt costs, ground rental payments and real estate brokerage and leasing commissions incurred by Landlord; (ii) costs incurred for Landlord&#8217;s general overhead and any property or asset management fee other than as expressly set
      forth in this Lease; (iii) costs of selling or financing any of Landlord&#8217;s interest in the Premises; (iv) costs incurred by Landlord which are reimbursed by property insurance proceeds actually received by Landlord where such proceeds result from a
      claim subject to the provisions of Section 6.2.3. below; and (v) reserves in excess of commercially reasonable amounts for comparable properties (and such reserves shall only be payable by Tenant if required by Landlord&#8217;s lender or in accordance with
      commercially reasonable business practices for comparable properties).</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Payments to Third
        Parties</u>. Subject to <u>Section 2.2.3(c)</u> below, Landlord and Tenant recognize that there may be recurring payments to third parties, including governmental entities, for various items including inspections of storm water retention areas,
      inspections of pump stations, fees for storm water runoff, and assessments for maintenance and repairs under a Title Instrument (as defined below). Tenant is solely responsible for paying any fees or expenses imposed by governmental regulations or
      third parties, including those that may be required to obtain, modify and maintain compliance with any permits, licenses and approvals required by Applicable Laws, including for the use of and operation at the Premises by Tenant for the Permitted
      Use, or allocated to the Premises under any such Title Instrument. Tenant acknowledges that matters of the type contemplated by this Section may not be known to Landlord until after this Lease has been signed by Landlord and Tenant.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.3.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Title Instruments</u>.
      In addition to the foregoing, during the term of this Lease, Tenant shall timely perform all obligations of the owner of the Premises under, and pay all expenses which the owner of the Premises may be required to pay in accordance with any
      declarations, covenants, conditions and restrictions or reciprocal easement agreements or any other documents or instruments that are of record now and affect the Premises (or of record in the future if created or filed by or with the consent of
      Tenant), including, without limitation, any documents or instruments recorded in connection with any Future Development (referred to collectively herein as the &#8220;<b>Title Instruments</b>&#8221;); provided, however, Tenant need not pay any debt service on
      loans that encumber the fee estate and that do not encumber Tenant&#8217;s leasehold estate and Tenant need not pay any rent on any lease that is senior in priority to this Lease. Tenant promptly shall comply with all of the terms and provisions of all
      Title Instruments, including all insurance requirements, regardless of whether any such requirements exceed the requirements otherwise set forth in this Lease. Notwithstanding the foregoing, except as provided in Section 10.5, Landlord shall not
      enter into new Title Instruments or modify existing Title Instruments during the Term without Tenant&#8217;s prior written consent, which may be withheld in Tenant&#8217;s reasonable discretion; provided, however, that Tenant&#8217;s prior written consent shall not be
      required with respect to (i) any financing obtained by Landlord secured by Landlord&#8217;s interest in the Premises, (ii) Title Instruments necessary to effectuate transfers to third-party purchasers of the Premises, or (iii) any new Title Instruments or
      the modification of existing Title Instruments that do not (x) materially and adversely affect Tenant&#8217;s use or occupancy of the Premises or (y) impose any fees or costs that would be payable by Tenant unless Landlord agrees to pay such fees.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">8</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Interest and Late
        Charge</u>. If Tenant fails to pay Rent as and when due and such failure continues for three (3) business days following written notice from Landlord, then, together with each payment of Rent that Tenant pays to Landlord after such payment is due,
      Tenant shall pay to Landlord the Late Charge (as defined below) and interest calculated on the amount of such payment over the period commencing on the day immediately following the day on which such payment was due and ending on the day on which
      Tenant pays to Landlord such payment at the rate of the lesser of six percent (6%) over the &#8220;Prime Rate&#8221; announced from time to time by Bank of America or its successor or the maximum lawful rate of interest. Notwithstanding the foregoing, Landlord
      shall not be required to provide prior notice of Tenant&#8217;s failure to pay Base Rent or any recurring obligation to pay Rent more than once during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be subject to the
      Late Charge and default interest provided above if Tenant fails to pay the amount when due and such failure continues for three (3) business days after the due date. &#8220;<b>Late Charge</b>&#8221; means, in respect of any such payment, five percent (5%) of
      such payment. In addition, Tenant shall pay to Landlord a reasonable fee for any checks returned by Tenant&#8217;s bank for any reason.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.5</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Security Deposit/Letter of Credit</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.5.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Concurrently with
      Tenant&#8217;s execution of this Lease, and in lieu of a cash security deposit, Tenant shall provide a letter of credit (the &#8220;<b>Letter of Credit</b>&#8221;) in the amount set forth as the &#8220;Security Deposit/Letter of Credit&#8221; in the Basic Lease Information. Any
      cash security deposit drawn from the Letter of Credit may be mingled with other funds of Landlord and no fiduciary relationship shall be created with respect to such deposit, nor shall Landlord be liable to pay Tenant interest thereon.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">9</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">2.5.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Letter of Credit (i) shall be
      irrevocable and shall be issued by a commercial bank that has a financial condition reasonably acceptable to Landlord and that is otherwise an Eligible Bank (as defined below) and has an office in San Francisco, California that accepts requests for
      draws on the Letter of Credit; provided, Silicon Valley Bank shall be deemed an approved issuer of the Letter of Credit so long as Silicon Valley Bank remains an Eligible Bank, (ii) shall require only the presentation to the issuer (which may be in a
      location other than San Francisco if permitted on the basis of a fax or electronic submittal only) a certificate of the holder of the Letter of Credit stating that Landlord is entitled to draw on the Letter of Credit pursuant to the terms of the
      Lease, (iii) shall be payable to Landlord or its successors in interest as the Landlord and shall be freely transferable without cost to any such successor or any lender holding a collateral assignment of Landlord&#8217;s interest in the Lease, (iv) shall
      be for an initial term of not less than one year and contain a provision that such term shall be automatically renewed for successive one-year periods unless the issuer shall, at least forty five (45) days prior to the scheduled expiration date, give
      Landlord notice of such nonrenewal, (v) shall be transferrable by Landlord without any cost to Landlord or the transferee (or, if there is a transfer fee, Tenant shall pay such fee and such transfer shall not be conditioned upon payment of such fee),
      and (vi) shall otherwise be in form and substance reasonably acceptable to Landlord. Notwithstanding the foregoing, the term of the Letter of Credit for the final period shall be for a term ending not earlier than the date forty-five (45) days after
      the last day of the Term. In the event that the issuer ceases to be reasonably acceptable to Landlord, due to a deterioration in its financial condition or change in status that threatens to compromise Landlord&#8217;s ability to draw on the Letter of
      Credit as determined in good faith by Landlord or otherwise by its failure to be an Eligible Bank, then Tenant shall provide a replacement Letter of Credit from an issuer satisfying the terms of this <u>Section 2.5.2</u> within thirty (30) days
      after Landlord&#8217;s notice of such event. &#8220;<b>Eligible Bank</b>&#8221; shall mean shall mean a commercial or savings bank organized under the laws of the United States or any state thereof or the District of Columbia and having total assets in excess of
      $1,000,000,000.00 that shall be a financial institution having a rating of not less than BBB or its equivalent by Standard and Poors Corporation and subject to a Thompson Watch Rating of C or better.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.5.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Letter of Credit
      shall be held by, or for the benefit of Landlord, as security for the performance of the provisions hereof by Tenant, and if the Letter of Credit or portion thereof is applied by Landlord for the payment of any Rent or any other sum in default, then
      Tenant shall, upon demand therefor, restore the Letter of Credit to its original amount as provided in <u>Section 2.5.1</u> above. Tenant hereby irrevocably waives and relinquishes any and all rights, benefits, or protections, if any, Tenant now
      has, or in the future may have under any provision of law which (i) establishes the time frame by which a landlord must refund a security deposit under a lease, or (ii) provides that a landlord may claim from a security deposit only those sums
      reasonably necessary to remedy defaults in the payment of rent, or to repair damage caused by a tenant or to clean the subject premises, as required and subject to the provisions of this Lease. Tenant acknowledges and agrees that (A) any statutory
      time frames for the return of a security deposit are superseded by the express period identified in this <u>Section 2.5</u>, and (B) rather than be so limited, Landlord may claim from the security deposit (i) any and all sums expressly identified in
      this <u>Section 2.4</u>, above, and (ii) any additional sums reasonably necessary to compensate Landlord for any and all losses or damages caused by Tenant&#8217;s default of this Lease, including, but not limited to, all damages or rent due upon
      termination of this Lease.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">10</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">2.5.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; Landlord shall be entitled to draw upon the
      Letter of Credit for its full amount or any portion thereof if (a) Tenant shall fail to perform any of its obligations under the Lease after the expiration of any applicable notice and cure period, or fail to perform any of its obligations under the
      Lease and transmittal of a default notice or the running of any cure period is barred or tolled by Applicable Law, or fail to perform any of its obligations under the Lease and any applicable notice and cure period would expire after the expiration
      of the Letter of Credit, or (b) not less than thirty (30) days before the scheduled expiration of the Letter of Credit, Tenant has not delivered to Landlord a new Letter of Credit in accordance with this Section; provided no such delivery shall be
      required if the Letter of Credit provides for automatic renewals in compliance with <u>Section 2.5.2</u>, and the issuer of the Letter of Credit has not sent a notice of non-renewal. Without limiting the generality of the foregoing, Landlord may,
      but shall not be obligated to, draw on the Letter of Credit from time to time in the event of a bankruptcy filing by or against Tenant and/or to compensate Landlord, in such order as Landlord may determine, for all or any part of any unpaid rent, any
      damages arising from any termination of the Lease in accordance with the terms of the Lease, and/or any damages arising from any rejection of the Lease in a bankruptcy proceeding commenced by or against Tenant. Landlord may, but shall not be
      obligated to, apply the amount so drawn to the extent necessary to cure Tenant&#8217;s failure.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">2.5.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; Any amount of the Letter
      of Credit drawn in excess of the amount applied by Landlord to cure any such failure shall be held by Landlord as a cash security deposit for the performance by Tenant of its obligations under the Lease. If Tenant shall fail to perform any of its
      obligations under the Lease, Landlord may, but shall not be obliged to, apply the cash security deposit to the extent necessary to cure Tenant&#8217;s failure. After any such application by Landlord of the Letter of Credit or cash security deposit, as the
      case may be, Tenant shall reinstate the Letter of Credit to the amount originally required to be maintained under the Lease, within ten (10) business days of Landlord&#8217;s demand. Provided that Tenant is not then in default under the Lease, and no
      condition exists or event has occurred that after the expiration of any applicable notice or cure period would constitute such a default, within forty five (45) days after the later to occur of (i) the payment of the final Rent due from Tenant or
      (ii) the later to occur of the Term Expiration Date or the date on which Tenant surrenders the Premises to Landlord in compliance with Section 20 of the Lease, the Letter of Credit and any cash security deposit, to the extent not applied, shall be
      returned to the Tenant, without interest, and Landlord, upon request, shall confirm termination of the Letter of Credit with the issuer thereof.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">2.5.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; In the event of a sale of the Buildings or
      lease, conveyance or transfer of the Buildings, Landlord shall transfer the Letter of Credit or cash security deposit to the transferee. Upon such transfer, the transferring Landlord shall be released by Tenant from all liability for the return of
      such security, and Tenant agrees to look to the transferee solely for the return of said security. The provisions hereof shall apply to every transfer or assignment made of the security to such a transferee. Tenant further covenants that it will not
      assign or encumber or attempt to assign or encumber the Letter of Credit or the monies deposited herein as security, and that neither Landlord nor its successors or assigns shall be bound by any assignment, encumbrance, attempted assignment or
      attempted encumbrance.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">11</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">2.5.7&#160;&#160;&#160;&#160;&#160;&#160;&#160; Landlord and Tenant acknowledge and agree
      that in no event or circumstance shall the Letter of Credit, any renewal thereof or substitute therefor or the proceeds thereof be (i) deemed to be or treated as a security deposit within the meaning of California Civil Code Section 1950.7, (ii)
      subject to the terms of such Section 1950.7, or (iii) intended to serve as a security deposit within the meaning of such Section 1950.7. The parties hereto (A) recite that the Letter of Credit is not intended to serve as a security deposit and such
      Section 1950.7 and any and all other laws, rules and regulations applicable to security deposits in the commercial context (&#8220;<b>Security Deposit Laws</b>&#8221;) shall have no applicability or relevancy thereto, and (B) waive any and all rights, duties and
      obligations either party may now or, in the future, will have relating to or arising from the Security Deposit Laws. Notwithstanding the foregoing, to the extent California Civil Code 1950.7 in any way: (a) is determined to be applicable to this
      Lease or the Letter of Credit (or any proceeds thereof); or (b) controls Landlord&#8217;s rights to draw on the Letter of Credit or apply the proceeds of the Letter of Credit to any amounts due under this Lease or any damages Landlord may suffer following
      termination of this Lease, then Tenant fully and irrevocably waives the benefits and protections of Section 1950.7 of the California Civil Code, it being agreed that Landlord may recover from the Letter of Credit (or its proceeds) all of Landlord&#8217;s
      damages under this Lease and California law including, but not limited to, any damages accruing upon the termination of this Lease in accordance with this Lease and Section 1951.2 of the California Civil Code.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: bold 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article
      3<br>
      USE, COMPLIANCE WITH LAWS, HAZARDOUS MATERIALS, DOGS</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Use</u>. Tenant shall use the Premises
      solely for the Permitted Use, in a manner consistent with first-class life science buildings, and shall comply (and ensure that the Premises at all times comply) with all Applicable Laws. Tenant shall be solely responsible for the securing,
      modifying, maintaining, and compliance with any and all permits, licenses and approvals required or that may be required or otherwise in effect for the Permitted Use and under Environmental Laws in connection with Tenant&#8217;s use and operation of the
      Premises. Tenant shall not commit, or allow to commit, any waste of or injury to the Premises or create, maintain or exacerbate any nuisance thereon or therefrom. Landlord agrees to reasonably cooperate with Tenant, at Tenant&#8217;s sole cost and expense,
      in obtaining any permits, licenses and approvals required by Applicable Laws for the use of and operation at the Premises by Tenant for the Permitted Use, including, without limitation, by executing or joining in the execution of such applications
      and other documentation (the form and content of which shall be subject to Landlord&#8217;s reasonable approval) in Landlord&#8217;s name, solely as and because Landlord is the fee simple owner of the Premises, as may be necessary for obtaining such permits,
      licenses and approvals, all without cost or liability to Landlord. Tenant shall operate in a first-class manner and shall not exceed the density limit for the Buildings under Applicable Laws. Tenant shall not commit waste or cause a public nuisance.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Compliance with
        Applicable Laws</u>. Tenant shall comply with all Applicable Laws and any agreements between Tenant and third parties with respect to the Premises and Tenant&#8217;s operation at the Premises. It is intended that the Tenant bear the sole risk of all
      present or future Applicable Laws, regulations and orders affecting the Premises, and the Landlord shall not be liable for their enforcement. Should there be any material noncompliance or alleged material noncompliance by Tenant with Applicable Laws
      or agreements between Tenant and third parties with respect to the Premises and Tenant&#8217;s operation at the Premises, Tenant shall promptly notify Landlord in writing of such actual or alleged noncompliance, which notice shall include (i) documentation
      that such actual or alleged noncompliance has been fully addressed and eliminated or, (ii) if such actual or alleged noncompliance has not been fully addressed and eliminated, a schedule to fully and expeditiously address and eliminate such actual or
      alleged noncompliance. The giving of such notice shall not relieve Tenant of any liability to Landlord or others for such actual or alleged noncompliance. To ensure Tenant&#8217;s compliance with Applicable Laws and Tenant&#8217;s performance of Tenant&#8217;s
      management, repair, maintenance, and compliance obligations hereunder, upon reasonable notice to Tenant and subject to and in accordance with Applicable Laws and reasonable confidentiality requirements pertaining to Tenant&#8217;s operations (provided such
      requirements do not impair or delay Landlord&#8217;s rights under this Section), Landlord may inspect or cause non-invasive independent third party inspections of the facility and Tenant&#8217;s operation to confirm compliance with Applicable Laws and Tenant&#8217;s
      management, repair, maintenance, and compliance obligations hereunder, at Landlord&#8217;s expense, except as otherwise provided in Section 3.3.7.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">12</font></div>
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10 Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Hazardous Materials</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant, and any of
      Tenant&#8217;s assignees, sublessees, licensees, agents, servants, employees, invitees and contractors (or any of Tenant&#8217;s assignees, sublessees and/or licensees respective agents, servants, employees, invitees and contractors) (collectively, &#8220;<b>Tenant
        Parties</b>&#8221;; any of them, a &#8220;<b>Tenant Party</b>&#8221;) (a) shall not, and shall not permit at any time, the handling, use, manufacture, release, storage, or disposal of Hazardous Materials in or about any portion of the Premises in violation of
      Applicable Laws, (b) shall always manage, handle, use, store, and dispose of such Hazardous Materials in a safe manner, according to prudent industry practice, and in compliance with Applicable Laws, and (c) shall at all times have any and all
      required permits, licenses and approvals required for or in connection with, the use and handling of Hazardous Materials at the Premises and at all times be in compliance with such required permits, licenses and approvals. &#8220;<b>Hazardous Materials</b>&#8221;
      means (a) any and all substances (whether solid, liquid or gas) defined, listed or otherwise classified or regulated as &#8220;biological compounds&#8221;, &#8220;bio-hazardous wastes&#8221;, &#8220;radiological elements&#8221;, &#8220;hazardous wastes,&#8221; &#8220;hazardous materials,&#8221; &#8220;hazardous
      substances,&#8221; &#8220;toxic substances,&#8221; &#8220;pollutants,&#8221; &#8220;contaminants,&#8221; &#8220;radioactive materials&#8221;, &#8220;toxic pollutants&#8221;, &#8220;solid wastes,&#8221; or other similar designations in, or otherwise subject to regulation under Environmental Laws, and (b) any other substances,
      constituents or wastes that are deemed to have a negative impact on human health or the environment, whether or not naturally occurring, or that are subject to Environmental Law, now or hereafter in effect, including but not limited to (A) petroleum,
      (B) refined petroleum products, (C) waste oil, (D) waste aviation or motor vehicle fuel and their byproducts, (E) asbestos, (F) lead in water, paint or elsewhere, (G) radon, (H) Polychlorinated Biphenyls (PCBs), (I) urea formaldehyde, (J) volatile
      organic compounds (VOC), (K) total petroleum hydrocarbons (TPH), (L) benzene derivative (BTEX), (M) poly- and perfluoroalkyl substances and other emerging contaminants, and (N) petroleum byproducts. Hazardous Materials further includes flammables,
      explosives, corrosive materials, radioactive materials, materials capable of emitting toxic fumes, hazardous wastes, toxic wastes or materials, and other similar substances, petroleum products and derivatives, and any substance subject to regulation
      by or under any Environmental Law. As between Landlord and Tenant, Tenant is deemed to be the operator of the Premises, the generator of any Hazardous Materials waste present at or generated at the Premises or as part of Tenant&#8217;s operations, and the
      owner of all Hazardous Materials at the Premises at any and all times during the Term. On or before the expiration or earlier termination of this Lease, Tenant shall remove from the Premises all Hazardous Materials introduced to the Premises by
      Tenant, any other Party or any other party other than Landlord during the Term of the Lease, regardless of whether such Hazardous Materials are included on the Hazardous Materials List or present at the Premises in concentrations which require
      removal under Applicable Laws. As used herein, the term &#8220;<b>Contamination</b>&#8221; means the presence of Hazardous Materials in the air, &#8206;soil, surface and/or ground water in, on or under the Premises and/or any adjacent property at levels &#8206;above those
      permitted by applicable Environmental Laws.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">13</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; Landlord acknowledges
      that it is not the intent of this <u>Section 3.3</u> to prohibit Tenant from using the Premises for the Permitted Use. Tenant may operate its business according to best industry practices so long as the use or presence of Hazardous Materials is
      strictly and properly monitored according to all then applicable Environmental Laws, all Hazardous Materials at the Premises are used in the operation of Tenant&#8217;s business, and such use is consistent with similar first-class facilities engaged in the
      Permitted Use in the greater San Diego County area. Notwithstanding the foregoing, Tenant shall have no right to install any underground storage tanks at the Premises unless Landlord has given Tenant its written consent to do so, which consent may be
      withheld in Landlord&#8217;s sole and absolute discretion. In conducting its research activities using Hazardous Materials, Tenant shall not perform work at or above the risk category Biosafety Level 3 as established by the Department of Health and Human
      Services publication Biosafety in Microbiological and Biomedical Laboratories (5th Edition) (as it may be or may have been further revised, the &#8220;<b>BMBL</b>&#8221;) or such nationally recognized new or replacement standards as Landlord may reasonable
      designate, without the prior written approval of Landlord, which approval shall not be unreasonably withheld, conditioned, or delayed (and if such change in Tenant&#8217;s operation requires the approval of Landlord&#8217;s lender, the lender&#8217;s denial of
      approval shall be deemed a reasonable basis for Landlord to deny its approval); provided, however, Landlord&#8217;s approval of any operation above the risk category Biosafety Level 3 shall be in Landlord&#8217;s sole discretion. Tenant shall comply with all
      applicable provisions of the standards of the BMBL to the extent applicable to Tenant&#8217;s operations in the Premises.</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">3.3.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; As a material inducement to Landlord to
      allow Tenant to use Hazardous Materials in connection with its business, Tenant agrees to deliver to Landlord prior to the Commencement Date a list identifying each type of Hazardous Materials (other than ordinary office and cleaning supplies used in
      cleaning of the office spaces within the Building) to be brought upon, kept, used, stored, handled, treated, generated on, or released or disposed of from, the Premises and setting forth any and all governmental approvals or permits required in
      connection with the presence, use, storage, handling, treatment, generation, release or disposal of such Hazardous Materials on or from the Premises (&#8220;<b>Hazardous Materials List</b>&#8221;). Upon Landlord&#8217;s request (not more than once per year, unless
      Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>, a release or threatened release of Hazardous Materials has occurred, or in connection with a sale, financing, refinancing, or recapitalization of
      Landlord&#8217;s interest in the Premises), or any time that Tenant is required to deliver a Hazardous Materials List to any governmental authority (e.g., the fire department) or an insurer in connection with Tenant&#8217;s use or occupancy of the Premises,
      Tenant shall deliver to Landlord a copy of such Hazardous Materials List. Tenant shall deliver to Landlord true and correct copies of the following documents (the &#8220;<b>Haz Mat Documents</b>&#8221;) relating to the use, storage, handling, treatment,
      generation, release or disposal of Hazardous Materials prior to the Commencement Date, or if unavailable at that time, concurrent with the receipt from or submission to a governmental authority: permits; licenses, approvals; reports and
      correspondence; storage and management plans; notice of violations of any Applicable Laws; fire safety plans; spill response plans; plans relating to the installation of any storage tanks to be installed in or under the Premises (provided, said
      installation of tanks shall only be permitted after Landlord has given Tenant its written consent to do so, which consent may be withheld in Landlord&#8217;s sole and absolute discretion with respect to underground storage tanks); all closure plans or any
      other documents required by any and all governmental authorities for any storage tanks installed in, on or under the Premises for the closure of any such tanks; and a Surrender Plan (to the extent surrender in accordance with Section 3.3.9 cannot be
      accomplished in three (3) months). Tenant is not required, however, to provide Landlord with any portion(s) of the Haz Mat Documents containing proprietary information of a proprietary nature that, in and of themselves, do not contain a reference to
      any Hazardous Materials or hazardous activities. It is not the intent of this Section to provide Landlord with information that could be detrimental to Tenant&#8217;s business should such information become possessed by Tenant&#8217;s competitors.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">14</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except to the extent
      caused by the gross negligence or willful misconduct of, or breach of contract by, Landlord or Landlord Parties, Tenant releases Landlord and Landlord Parties from and agrees to indemnify, defend and hold Landlord and Landlord Parties harmless for,
      from and against any and all actions (including, without limitation, remedial or enforcement actions of any kind, administrative or judicial proceedings, and orders or judgments arising out of or resulting therefrom), costs, claims, damages
      (including, without limitation, punitive damages and damages based upon diminution in value of the Premises, or the loss of, or restriction on, use of the Premises), expenses (including, without limitation, legal, consultants&#8217; and experts&#8217; fees,
      court costs and amounts paid in settlement of any claims or actions), fines, forfeitures or other civil, administrative or criminal penalties, injunctive or other relief (whether or not based upon personal injury, property damage, or Contamination
      of, or adverse effects upon, the environment, water tables or natural resources), liabilities or losses (i) that arise prior to, during, or after the Term, as a result of the presence, suspected presence, release, or suspected release of any
      Hazardous Materials in or into the environment, including the air, soil, surface water, or groundwater at, on, about, under, emanating to or from, having emanated to or from, or within the Premises, or any portion thereof caused or exacerbated by, or
      otherwise attributable to, Tenant or any other party (other than Landlord or Landlord Parties) prior to the date that Tenant vacates the Premises in the condition required following the termination or earlier expiration of the Term, or (ii) that
      arise prior to, during, or after the Term, as a result of the breach by Tenant of any of its obligations under this Section 3.3, including in each case, without limitation, the cost of assessment, containment and/or removal of any such Hazardous
      Materials, the reasonable and necessary cost of any actions taken in response to a release of any such Hazardous Materials so that it does not migrate or otherwise cause or threaten danger to present or future public health, safety, welfare or the
      environment, and costs incurred to comply with Environmental Laws in connection with all or any portion of the Premises or the operation thereof (or any surrounding areas for which Tenant or Landlord has any legal liability or obligation) during the
      Term.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">15</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; EXCEPT AS OTHERWISE
      PROVIDED FOR HEREIN, LANDLORD LEASES AND WILL LEASE, AND TENANT TAKES AND WILL TAKE, THE PREMISES IN AN ENVIRONMENTALLY &#8220;AS IS&#8221; CONDITION, AND TENANT ACKNOWLEDGES THAT LANDLORD HAS NOT MADE AND WILL NOT MAKE, NOR SHALL LANDLORD BE DEEMED TO HAVE
      MADE, ANY WARRANTY OR REPRESENTATION, EXPRESS OR IMPLIED, WITH RESPECT TO THE ENVIRONMENTAL CONDITION OF THE PREMISES, INCLUDING ANY WARRANTY OR REPRESENTATION AS TO FITNESS OF THE PREMISES FOR ANY PARTICULAR USE OR PURPOSE, AS TO THE PRESENCE OR
      ABSENCE OF ANY HAZARDOUS MATERIALS, LATENT OR PATENT, ANY ENVIRONMENTAL CONDITION, KNOWN OR UNKNOWN, OR ANY AIR, SOIL, SOIL GAS, OR GROUNDWATER CONDITION, IT BEING AGREED THAT ALL RISKS AND LIABILITY INCIDENT TO ANY OF THE FOREGOING ARE TO BE BORNE
      BY TENANT</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">3.3.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant hereby represents and warrants to
      Landlord that (i) neither Tenant nor any of its legal predecessors has been required by any prior landlord, lender or governmental authority at any time to take remedial action in connection with Hazardous Materials contaminating the natural
      environment, which contamination was caused or permitted by Tenant or such predecessor or resulted from Tenant&#8217;s or such predecessor&#8217;s acts, omissions, or use or occupation of the property in question, and (ii) Tenant is not subject to any
      enforcement order issued, or regulatory proceedings or prosecution commenced, by any governmental authority in connection with the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials (including, without
      limitation, any order related to the failure to make a required reporting to any governmental authority).</font></p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10 Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.7&#160;&#160;&#160;&#160;&#160;&#160;&#160; Upon prior notice and
      using reasonable efforts to coordinate with Tenant, Landlord shall have the right but not the obligation to conduct annual tests (or at any time Landlord has a reasonable belief that Tenant is not in compliance with this <u>Section 3.3</u>) of the
      Premises including, without limitation, intrusive tests of the subsurface soil and/or ground water, to determine whether any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation. Landlord shall pay the cost of such
      test of the Premises; provided, however, that if such tests show any Contamination of the Premises has occurred as a result of Tenant&#8217;s use or occupation, Tenant shall pay the cost of such test. In connection with such testing, upon the request of
      Landlord, Tenant shall deliver to Landlord or its consultant such non-proprietary information concerning the use, storage, handling, treatment, generation, release or disposal of Hazardous Materials in or about the Premises by Tenant or any Tenant
      Party as Landlord may reasonably request. If Contamination has occurred for which Tenant is liable under this Section 3.3, Tenant shall pay all costs to conduct such tests. Tenant shall, at its sole cost and expense, promptly and satisfactorily
      remediate any Contamination identified by such testing in accordance with all Environmental Laws. Landlord&#8217;s receipt of or satisfaction with any environmental assessment in no way waives any rights that Landlord may have against Tenant.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">16</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.8&#160;&#160;&#160;&#160;&#160;&#160;&#160; Furthermore, upon the
      expiration of the Term or earlier termination of Tenant&#8217;s right of possession, Tenant shall surrender the Premises to Landlord free of Hazardous Materials brought upon, kept, used, stored, handled, treated, generated in, or released or disposed of
      from, the Premises by any person other than Landlord (collectively, &#8220;<b>Tenant&#8217;s Hazardous Materials</b>&#8221;) and released of any license, clearance or other authorization or requirement of any kind required to enter into and restore the Premises issued
      by any governmental authority having jurisdiction over the use, storage, handling, treatment, generation, release, disposal, removal or remediation of Hazardous Materials in, on or about the Premises (collectively referred to herein as &#8220;<b>Hazardous
        Materials Clearances</b>&#8221;). At least three (3) months prior to the surrender of the Premises or such earlier date as Tenant may elect to cease operations at the Premises, Tenant shall deliver to Landlord a narrative description of the actions
      proposed (or required by any governmental authority) to be taken by Tenant in order to surrender the Premises (including any Alterations permitted by Landlord to remain in the Premises) at the expiration or earlier termination of the Term, free from
      any residual impact from Tenant&#8217;s Hazardous Materials and otherwise released for unrestricted use and occupancy (the &#8220;<b>Surrender Plan</b>"). Such Surrender Plan shall be accompanied by a current listing of (i) all Hazardous Materials licenses and
      permits held by or on behalf of any Tenant Party with respect to the Premises, and (ii) all Hazardous Materials used, stored, handled, treated, generated, released or disposed of from the Premises, and shall be subject to the review and reasonable
      approval of Landlord&#8217;s environmental consultant. In connection with the review and approval of the Surrender Plan, upon the request of Landlord, Tenant shall deliver to Landlord or its consultant such additional non-proprietary information concerning
      Tenant&#8217;s Hazardous Materials as Landlord shall reasonably request. On or before such surrender, Tenant shall deliver to Landlord evidence that the approved Surrender Plan shall have been satisfactorily completed and Landlord shall have the right,
      subject to reimbursement at Tenant&#8217;s expense as set forth below, to cause Landlord&#8217;s environmental consultant to inspect the Premises and perform such additional procedures, including without limitation intrusive subsurface testing of soil and/or
      ground water, as may reasonably be deemed necessary to confirm that the Premises are, as of the effective date of such surrender or early termination of the Lease, free from any Tenant&#8217;s Hazardous Materials. Tenant shall reimburse Landlord, as
      Additional Rent, for the actual out-of-pocket expense incurred by Landlord for Landlord&#8217;s environmental consultant to review the Surrender Plan and to visit the Premises and verify satisfactory completion of the same, which cost shall not exceed
      $5,000 (which amount shall be increased by the same percentage as the Index as of each Adjustment Date). Landlord shall have the unrestricted right to deliver such Surrender Plan and any report by Landlord&#8217;s environmental consultant with respect to
      the surrender of the Premises to third parties on a need-to-know basis.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.9&#160;&#160;&#160;&#160;&#160;&#160;&#160; If Tenant shall fail
      to prepare or submit a Surrender Plan approved by Landlord, or if Tenant shall fail to complete the approved Surrender Plan, or if such Surrender Plan, whether or not approved by Landlord, shall fail to adequately address any Tenant&#8217;s Hazardous
      Materials in, on or about the Premises, Landlord shall have the right to take such actions as Landlord may reasonably deem appropriate to assure that the Premises are surrendered free from any Tenant&#8217;s Hazardous Materials, the cost of which actions
      shall be reimbursed by Tenant as Additional Rent.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.3.10&#160;&#160;&#160; Tenant&#8217;s obligations
      under this Section 3.3 shall survive the expiration or earlier termination of the Lease. During any period of time after the expiration or earlier termination of this Lease required by Tenant or Landlord to complete the removal from the Premises of
      any Hazardous Materials (including, without limitation, the release and termination of any licenses or permits restricting the use of the Premises and the completion of the approved Surrender Plan), Tenant shall continue to pay the full Rent in
      accordance with this Lease for any portion of the Premises not relet by Landlord in Landlord&#8217;s sole discretion, which Rent shall be prorated daily.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">17</font></div>
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Alterations</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Consent</u>. Tenant
      may make any alterations, improvements, additions or changes to the Premises (collectively &#8220;Alterations&#8221;) that meet all of the following criteria without first obtaining Landlord&#8217;s Consent: (a) the Alterations are cosmetic, (b) the Alterations are
      non-structural and do not affect the mechanical systems of the Building, (c) the Alterations cost less than $1,000,000.00 per project (which amount shall be increased by the same percentage as the Index as of each Adjustment Date); and (d) after the
      Alterations, the Premises will continue to be used for the Permitted Use (collectively, Alterations meeting the criteria of (a)-(d), &#8220;Minor Alterations&#8221;). Any Alterations that are not Minor Alterations shall be subject to Landlord&#8217;s approval, such
      approval not to be unreasonably withheld, conditioned or delayed. Tenant shall reimburse Landlord for any third-party expenses reasonably incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s plans for
      Alterations and Tenant&#8217;s performance thereof. Notwithstanding the foregoing, Tenant shall have the right to construct the renovation of the conference center located at 2850 Gazelle Court (the &#8220;Conference Center Alterations&#8221;), at Tenant&#8217;s sole cost
      and expense, in accordance with the plans and specifications identified on <u>Exhibit H</u> attached hereto (the &#8220;CCA Plans&#8221;) and in accordance with all Applicable Laws, provided any modifications to the plans for the Conference Center Alterations
      that are not Minor Alterations, minor field work changes not requiring Tenant&#8217;s approval under the applicable construction contract for such Alterations, or changes that are required to comply with applicable law, shall require, in each case,
      Landlord&#8217;s approval, not to be unreasonably withheld, conditioned or delayed, and the Conference Center Alterations shall otherwise comply with this Section 3.4. Tenant hereby agrees to provide copies of all plans of such Alterations, regardless of
      whether Landlord&#8217;s consent is required. Tenant shall diligently and expeditiously complete any Alterations commenced. All Alterations shall become part of the realty constituting the Premises and shall belong to Landlord and shall not be removed by
      Tenant. If any Alteration (other than the Conference Center Alterations) is anticipated to cost more than $1,500,000, Landlord shall have the right to require Tenant to post a performance or payment bond in connection with any work or service done or
      purportedly done by or for the benefit of Tenant. Tenant acknowledges and agrees that all such work or service is being performed for the sole benefit of Tenant and not for the benefit of Landlord. Landlord shall, at the time it provides its approval
      for a proposed Alteration, advise Tenant whether the Alteration, or any portion thereof, is a Required Removable, as defined in Section 4.2.2.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Liens</u>. With
      respect to any Alterations, Tenant hereby agrees as follows: (a) Tenant shall not cause or permit any construction, mechanics&#8217; or other liens or encumbrances to be placed upon the Premises, or Tenant&#8217;s leasehold interest hereunder, whether in
      connection with any work or service done or purportedly done by or for the benefit of Tenant, its subtenants, or any other party acting under or through Tenant, or otherwise, (b) Tenant shall cause all Alterations to be constructed free of all liens,
      in accordance with all Applicable Laws and shall, upon Landlord&#8217;s request, deliver lien waivers to Landlord in the form required by Applicable Law, (c) Tenant shall pay the costs of the Alterations and so that Landlord, the Premises will be protected
      against any loss from any mechanic&#8217;s, materialmen&#8217;s, or other liens, and (d) prior to the commencement of the construction of any Alterations, Tenant shall give to Landlord evidence of the insurance required by <u>Section&#160;6.2.4</u>. Notwithstanding
      the foregoing or anything to the contrary in this Lease, Tenant may contest any lien if (i) such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord of such dispute,
      and (iii) such lien is fully bonded by Tenant to the reasonable satisfaction of Landlord and any Mortgagee. Tenant shall give Landlord notice at least fifteen (15) days prior to the commencement of any work in the Premises, other than any Alterations
      that are purely cosmetic.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">18</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Requirements</u>.
      Prior to starting work on any Alterations, Tenant shall furnish Landlord with two (2) complete sets of professionally prepared working drawings (which shall include any architectural, structural, electrical, mechanical, computer system wiring, and
      telecommunication plans, which shall all be in CAD or other electronic format if requested by Landlord), and will be consistent with the construction methods and procedures manual attached hereto as Exhibit K, as amended from time to time for the
      Premises (the &#8220;<b>Tenant Construction Manual</b>&#8221;); names of contractors reasonably acceptable to Landlord; required permits and approvals; and evidence of contractor&#8217;s and subcontractor&#8217;s insurance in amounts reasonably required by Landlord and
      naming as additional insureds the Landlord, the managing agent for the Premises, and such other Additional Insured Parties (as defined in Section 13) as Landlord may designate for such purposes. All Cable shall be clearly marked with adhesive plastic
      labels (or plastic tags attached to such Cable with wire) to show the purpose of such Cable (i) every six (6) feet in locations behind walls, beneath floors, and above ceilings (specifically including, but not limited to, the electrical room risers),
      and (ii) at the termination point(s) of such Cable. &#8220;<b>Cable</b>&#8221; shall mean and refer to any electronic, fiber, phone and data cabling and related equipment that is installed by or for the exclusive benefit of Tenant or any party acting under or
      through Tenant. Any changes to the plans and specifications, other than di minimus changes that are purely cosmetic, do not affect the Building structure or mechanical systems, and do not cause the cost of the Alterations to exceed $1,000,000 (which
      amount shall be increased by the same percentage as the Index as of each Adjustment Date), must also be submitted to Landlord for its approval. Prior to commencing Alterations, Tenant shall provide Landlord with a copy of the contract for the
      Alterations and evidence satisfactory to Landlord as to the existence of all necessary permits (to the extent not previously provided). Alterations shall be (a) constructed in a good and workmanlike manner, (b) consistent with first class standards,
      (c) consist of materials of a quality reasonably approved by Landlord, and Tenant shall ensure that no Alteration impairs any Building system, (d) performed by contractors or mechanics whose labor union affiliations are not incompatible with those
      &#8206;of any workers, contractors or subcontractors who may be employed, retained or engaged by the &#8206;Landlord for the development and making of any alterations at the Premises, and who are otherwise reasonably approved by Landlord, (e) in accordance with
      the Tenant Construction Manual, if any, and (f) designed and performed in accordance with all applicable Laws. It shall be deemed reasonable for Landlord to withhold its consent to any Alteration that adversely affects a Building&#8217;s roof, structure,
      or systems, that is inconsistent with a first-class life science building, that results in an increase in gross floor area at the Premises or alteration of any Building footprint, that would violate any certificate of occupancy for the Buildings or
      any other permits or licenses relating to the Buildings, that would reduce the utility of the Premises for life sciences laboratory, research, and manufacturing purposes, or that is otherwise inconsistent with the requirements of this Section. Tenant
      shall reimburse Landlord for any third-party expenses incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s plans for Alterations and Tenant&#8217;s performance thereof. Upon completion, Tenant shall furnish
      &#8220;as-built&#8221; plans (in CAD or other electronic format, if requested by Landlord) for Alterations, customary American Institute of Architects completion affidavits, full and final waivers of lien, any applicable certificate of occupancy for the space
      affected by such Alterations and other applicable municipal or local sign-offs and inspection reports, and any other items reasonably required by Landlord for closing out the particular work in question. Landlord&#8217;s approval of an Alteration shall not
      be deemed to be a representation by Landlord that the Alteration complies with Law or will not adversely affect any Building system.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">19</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Construction
        Oversight Fee</u>. With respect to any Alterations requiring Landlord&#8217;s consent under Section 3.4.1, Tenant shall pay Landlord a construction oversight fee (&#8220;<b>Construction Oversight Fee</b>&#8221;) equal to the sum of one percent (1%) of total hard and
      soft project costs, provided that Landlord&#8217;s obligations in connection with the Alterations are limited to oversight only and not direct management of the project. The Construction Oversight Fee shall be calculated based on hard and soft project
      costs for the Alterations that were approved by Landlord for the portion of work that has been performed and invoiced and shall be payable monthly in arrears concurrent with the approved hard and soft project costs for the Alterations during the
      applicable month.&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Completion</u>.
      Upon the completion of any Alterations, Tenant shall, to the extent applicable, promptly give to Landlord (a) a reproducible copy of the &#8220;as-built&#8221; drawings of such Alterations, (b) a certificate of completion executed on behalf of Tenant&#8217;s architect
      and/or engineering certifying completion of such Alterations in accordance with the respective plans and specifications, (c) a copy of the certificate of occupancy issued by the applicable governmental authorities with respect to such Alterations,
      and (d) copies of any warranties or guarantees with respect to such Alterations (and ensure that such warranties or guarantees are assignable to Landlord and/or run to both Landlord and Tenant&#8217;s benefit).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.4.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Ownership of
        Alterations</u>. Any Alterations shall belong to Tenant until the Termination Date, at which time the Alterations (other than Tenant&#8217;s Trade Fixtures (as hereinafter defined)) shall belong to Landlord; provided, however, in no event shall the
      Alterations be removed by Tenant prior to the Termination Date, except as expressly provided herein. For purposes of this Lease, &#8220;<b>Trade Fixtures</b>&#8221; shall mean a piece of equipment placed on the Premises owned by Tenant and used in Tenant&#8217;s trade
      or business. For the avoidance of doubt, Trade Fixtures shall not include, without limitation, Building systems and machinery, built-in cabinet work and/or lab benches, purpose-built mezzanine space, all HVAC, air handling, electrical, mechanical and
      plumbing equipment and related ducts, shafts, and conduits, all exterior venting fume hoods, walk-in freezers and refrigerators, clean-rooms, climatized rooms, electrical panels and power back-up distribution systems. The parties agree that Landlord
      will be treated for all purposes, including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other cost recovery deductions for federal tax purposes with respect to) any improvements, equipment, or personal
      property that were paid for, or reimbursed by, Landlord, including any allowance provided by Landlord, and Tenant will be treated for all purposes, including tax purposes, as the owner of (and will be the party entitled to claim depreciation or other
      cost recovery deductions for federal tax purposes with respect to) any improvements to the extent that the cost for such improvements were paid for by Tenant and to the extent any such costs exceed any allowance provided by Landlord. Unless required
      to adopt a contrary position as a result of an administrative or judicial proceeding, the parties shall take no action inconsistent with, the intentions set forth in this paragraph. The parties will provide each other with such cooperation as is
      reasonably necessary to implement the intentions of this paragraph.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">20</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Jeopardy of
        Insurance</u>. Tenant shall neither do nor omit to do anything that might result in the actual or threatened reduction or cancellation of or material adverse change in insurance carried by Landlord or Tenant on the Premises. If any such insurance
      is actually, or threatened to be, cancelled, reduced or materially adversely changed by an insurer as a result of the use or occupancy of the Premises or any article kept in or about the Premises or any act or omission of Tenant or any person for
      whom Tenant is in law responsible or any occupant of the Premises, and if Tenant fails to remedy the condition or the use or occupancy giving rise to such actual or threatened cancellation, reduction or change within three (3) business days after
      notice thereof, Landlord may, without limiting its other remedies for the default, enter upon the Premises and remedy the condition, use or occupancy giving rise to such actual or threatened cancellation, reduction or change, and Tenant shall pay to
      Landlord its cost of doing so within ten (10) days following invoice, plus an administrative fee equal to ten percent (10%) of such cost. Landlord shall not be liable for any damage to either the Premises or any property located on the Premises as a
      result of such entry.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Dogs</u>. Tenant
      shall be permitted to bring a reasonable number of non-aggressive, fully domesticated, properly licensed, fully vaccinated, and well behaved dogs, kept by Tenant&#8217;s employees as pets, into the Premises, provided and upon condition that: (a) all dogs
      shall be strictly controlled at all times, (b) dogs shall not be permitted to foul, damage or otherwise mar any part of the Buildings or Premises; and (c) while entering and exiting the Premises, all dogs shall be kept on leashes. Landlord may limit
      the number, weight, and breed of dogs that may be permitted in the Premises, and Landlord may implement other rules and regulations not inconsistent with this Section 3.6 that Landlord, in its sole discretion, deems reasonable or prudent. Tenant
      shall be responsible for any damage and additional cleaning costs and all other costs which may arise from the dogs' presence in the Buildings and on the Premises. Tenant shall be liable for, and hereby agrees to indemnify, defend and hold Landlord
      harmless from any and all claims arising from any and all acts (including but not limited to biting and causing bodily injury to, or damage to the property of, another lessee, sublessee, occupant, licensee, invitee, Landlord or an employee of
      Landlord) of, or the presence of, any dog in or about the Premises or the Buildings. Tenant shall promptly remove any dog waste and excrement from the Premises and Buildings. Dogs shall be strictly controlled and supervised at all times (including,
      without limitation, by being on leashes) by Tenant&#8217;s employees, with no less than one (1) such employee responsible for so controlling and supervising no more than two (2) dogs apiece. Within three (3) business days following Landlord&#8217;s request
      therefor, Tenant shall provide Landlord with reasonably satisfactory evidence showing that all current vaccinations have been received by any dogs permitted on the Premises. No dog shall be brought to the Premises if such dog is ill or contracts a
      disease that could potentially threaten the health or wellbeing of any person on the Premises (which diseases may include, without limitation, rabies, leptospirosis and lyme disease). Tenant shall not permit any objectionable dog related noises or
      odors to emanate from the Premises (as determined by Landlord in its sole discretion), and in no event shall any dog be at the Premises overnight or for any extended period of time. Tenant shall install and maintain dog waste bag dispensers in
      outdoor areas of the Premises, and all waste generated by any dogs in or about the Premises shall be promptly removed and disposed of (on no less than a daily basis) in trash receptacles. Any areas of the Premises affected by such waste shall be
      immediately cleaned and otherwise sanitized. Landlord may require Tenant to permanently ban any dog from the Premises if (i) any such dog exhibits aggressive behavior, damages or destroys property in the Premises, violates specific provisions of this
      Section, defecates or urinates in any non-outdoor area of the Project, or defecates in any outdoor area of the Project and Tenant fails to remove such waste in accordance with the terms of this Section, and (ii) any such dog is found by Landlord in
      its sole but good faith discretion to be a substantial, repeated nuisance to the Premises, and, in any such event, such substantial, repeated nuisance persists after at least two (2) written notices to Tenant from Landlord in any twelve (12) month
      period), then Landlord may terminate Tenant&#8217;s rights under this Section. Tenant shall promptly pay to Landlord, within thirty (30) days after demand, all costs incurred by Landlord that directly result from the presence of any of dogs in the
      Premises. Tenant&#8217;s right provided in this Section is personal only to the original named Tenant and/or any Permitted Transferee, shall not be exercisable by any other assignee, subtenant or other transferee of or successor to any portion of Tenant&#8217;s
      interest under the Lease or to the Premises.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">21</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">3.7&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>LEED Standards</u>.
      Tenant shall ensure that the Buildings meet at least the standard for a &#8220;Gold&#8221; rating under the U.S. Green Building Council&#8217;s Leadership in Energy and Environmental Design (&#8220;<b>LEED</b>&#8221;) rating system for a campus consisting of multiple buildings.
      In connection with the foregoing, Tenant shall reasonably cooperate with Landlord in its submission of all filings to obtain and maintain Gold or better LEED rating for the Buildings as a campus. Tenant shall reimburse Landlord for the costs to
      obtain and maintain such Gold or better LEED rating for the Buildings as a campus in an amount not to exceed in the aggregate more than $40,000.00 annually, including any discounts and credit that may be applied to reduce such costs. Tenant shall not
      be responsible for any costs to obtain LEED Gold or better certification for the Conference Center, individually, in connection with the campus designation of the Buildings (it being acknowledged that Tenant&#8217;s sole obligation with respect to the
      Conference Center Alterations, as shown in the CCA Plans, will be to meet the applicable California State and local standards for energy efficiency and environmental design). All Alterations, and any lighting installed by Tenant in the Premises,
      shall be designed, maintained, and installed in accordance with the requirements for LEED Gold or better campus certification, as the same may change from time to time If necessary to ensure compliance with the applicable LEED standards, Tenant
      further agrees to engage a qualified third party LEED or Green Globe Accredited Professional or similarly qualified professional during the design phase of any Alterations, in order to review all plans, material procurement, demolition, construction
      and waste management procedures to ensure they are in full conformance with the requirements to maintain the applicable LEED rating.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">22</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article 4<br>
      REPAIR AND MAINTENANCE; SERVICES</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tenant Repair and
        Maintenance Obligations</u>. The parties intend for this Lease to be absolutely triple net. Tenant shall be responsible for all repairs, replacements and maintenance of the Premises. Landlord shall have no obligation whatsoever to repair or
      maintain the Premises. Tenant shall repair and maintain the Premises in substantially the condition as exists as of the Effective Date of this Lease (and as it may be improved or altered thereafter), keep same in good order, condition and repair, and
      in compliance with Applicable Laws, ordinary wear and tear and casualty excepted, to the extent Tenant is not otherwise obligated to restore the same.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.2</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Condition of Premises on Surrender</u></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as otherwise
      provided in this <u>Section 4.2</u>, upon the Termination Date, all Alterations (other than Tenant&#8217;s Trade Fixtures) shall belong to Landlord without compensation, and title shall pass to Landlord under this Lease. On the Termination Date, Tenant
      shall give Landlord possession of the Premises, together with all such Alterations (other than Tenant&#8217;s Trade Fixtures), in the good, broom clean condition, free of all debris, excepting only ordinary wear and tear and damage that Tenant is not
      required to repair or restore under this Lease. On or prior to the Termination Date, Tenant shall also (a) remove all of Tenant&#8217;s furniture, Trade Fixtures, furnishings, equipment belonging to the Tenant, and other personal property (collectively,
      the &#8220;<b>Personalty</b>&#8221;), and (b) repair any damage caused by the removal of such Personalty. All of Tenant&#8217;s Personalty not so removed by Tenant, may be removed from the Premises by Landlord and stored, at Tenant&#8217;s sole risk and expense, and in any
      event, Landlord shall not be responsible for the value, preservation, or safekeeping thereof. Tenant shall pay to Landlord, upon demand, all reasonable expenses so incurred by Landlord, including the cost of repairing any damage caused by removal and
      storing such Personalty (collectively, &#8220;<b>Tenant&#8217;s Property</b>&#8221;). Any such Tenant&#8217;s Property not claimed by Tenant within sixty (60) days after Tenant&#8217;s surrender of the Premises shall, at Landlord&#8217;s option, be deemed either abandoned or conveyed
      by Tenant to Landlord under this Lease without further payment or credit by Landlord to Tenant. On the Termination Date, Tenant shall assign to Landlord all manufacturers&#8217; and contractors&#8217; warranties with respect to the Premises and the Alterations
      (including all fixtures therein or thereon but excluding Tenant&#8217;s Trade Fixtures) and Tenant shall use commercially reasonable efforts obtain the consent of the issuers of such warranties (which may include, without limitation, the payment of an
      assignment fee), to the extent that such consent is required for the assignment to Landlord.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; Landlord, at the time
      required by <u>Section 3.4.1</u>, by written notice to Tenant may require Tenant, at Tenant&#8217;s expense, to remove any Alterations or other affixed installations that, in Landlord&#8217;s reasonable judgment, are of a nature that are not customary office or
      life science improvements and would require removal and repair costs that are materially in excess of the removal and repair costs associated with standard improvements for the Permitted Use (&#8220;<b>Required Removables</b>&#8221;). Required Removables shall
      include, without limitation, internal stairways, raised floors, vaults, rolling file systems, structural alterations and modifications (including any slab penetrations) other than de minimis alterations and modifications associated with connection of
      other improvements to the structure of the Building or relocation of demising walls provided that the same are otherwise consistent with first class life science buildings, Tenant&#8217;s signage, supplemental systems (including HVAC), vivariums, and any
      Cable installed by or on behalf of Tenant that is not necessary for the proper functioning of any Alterations remaining in the Premises in accordance with this Lease. Notwithstanding the foregoing, any fixtures or improvements existing within the
      Premises on the Effective Date, or as shown on the CCA Plans, shall not be deemed Required Removables. The Required Removables shall be removed by Tenant before the expiration or earlier termination of this Lease in accordance with Section this
      Section 4.2, unless otherwise directed by Landlord. Landlord shall be treated as the owner of all Alterations (but, subject to Section 4.2.1, not any of Tenant&#8217;s Property, including any trade fixtures and equipment that are installed in a manner that
      will not damage the Premises when removed) during the term of the Lease, including for tax and depreciation purposes, but Tenant shall have the exclusive right to use the same subject to the terms of this Lease.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">23</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">4.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Services and
        Utilities</u>. Landlord shall not be obligated to furnish to the Premises any services or utilities (including, without limitation, janitorial services), and Tenant shall contract directly with the providers of all services and utilities Tenant
      desires to receive at the Premises, at Tenant&#8217;s sole cost and expense. Tenant shall have the right to add alternative electricity sources such as additional solar panels, the installation of which shall be subject to Section 3.4. Landlord is not
      responsible for the furnishing of, or any interruption, diminishment or termination of, services or utilities, whether due to the application of Laws, the failure of any equipment, the performance of maintenance, repairs, improvements or alterations,
      or utility interruptions, and no such interruption, diminishment, or termination shall render Landlord liable to Tenant, give rise to an abatement of Rent, or relieve Tenant from the obligation to fulfill any covenant or agreement. Except as
      expressly set forth in Article 9, below, Landlord shall in no event be required under any provision of this Lease or applicable Law to maintain or repair or to make any alterations, rebuildings, replacements, changes, additions or improvements on or
      off the Premises during the Term of this Lease. Tenant acknowledges that it shall be responsible for providing and procuring all other services necessary to its operations in and on the Premises. If Tenant (or any party claiming by, through or under
      Tenant) pays directly to the provider for any energy consumed at the Buildings, Tenant, promptly upon request, shall deliver to Landlord (or, at Landlord&#8217;s option, execute and deliver to Landlord an instrument enabling Landlord to obtain from such
      provider) any data about consumption that Landlord, in its reasonable judgment, is required to disclose to a prospective buyer, tenant or mortgage lender under California Public Resources Code &#167;25402.10 or any similar law. Further, Tenant hereby
      waives and releases its right to make repairs at Landlord&#8217;s expense under Sections 1932(1), 1933(4), 1941 and 1942 of the California Civil Code or any similar or successor laws now or hereinafter in effect. At Landlord&#8217;s request, Tenant shall provide
      Landlord information regarding Tenant&#8217;s energy usage at the Premises from time to time (provided that Landlord shall hold such information confidential to the extent Landlord is not required to disclose such information pursuant to Applicable Law,
      nothing in this sentence being deemed to prohibit Landlord from utilizing such information to make public statements about the sustainability profile or &#8220;green&#8221; nature of Landlord, or Landlord&#8217;s affiliates, properties).</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">24</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article



      5<br>
      ASSIGNMENT AND SUBLETTING</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.1</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>General Prohibition on Transfers</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Transfers Generally</u>.
      Tenant shall not, directly or indirectly, make a Transfer (as defined below), without Landlord&#8217;s consent, except as expressly set forth in this <u>Article 5</u>, and any purported Transfer that does not comply with the provisions of this <u>Article
        5</u> shall, at Landlord&#8217;s option, be deemed an Event of Default by Tenant and shall be voidable by Landlord. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or successor laws, now or hereinafter
      in effect, and all other remedies, including any right at law or equity to terminate this Lease in connection with Landlord&#8217;s withholding its consent to any Transfer, on its own behalf and on behalf of the proposed transferee. Landlord shall not
      unreasonably withhold, condition, or delay its consent to an assignment of this Lease or any sublet of the Premises, subject to the terms and conditions of this Article 5. Without limitation, it is agreed that Landlord&#8217;s consent shall not be
      considered unreasonably withheld if the proposed Transferee (defined below) (a) is a governmental entity, (b) is incompatible with the character of occupancy of a first class life sciences buildings, (c) is an entity with which the payment for the
      sublease or assignment is determined in whole or in part based upon its net income or profits, (d) would subject the Premises to a use that would: (i) involve increased personnel or wear upon the Buildings in a manner inconsistent with first-class
      life science buildings; (ii) require any addition to or material modification of the Premises or the Buildings in order to comply with building code or other governmental requirements; or (iii) involve a violation of the Permitted Use clauses of this
      Lease, or (e) if there is any other reasonable ground not stated above for withholding consent.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Clients



        and Business Partners</b>&#8221; means persons or entities who are not employees or agents of Tenant or its Affiliates but are occupying or using portions of the Premises and are either (i) performing services for Tenant as subcontractors under Tenant's
      contracts, (ii) personnel employed by persons or entities for whom Tenant is performing services on a contractual basis, or (iii) personnel employed by persons or entities with whom Tenant is engaged in a joint venture or joint teaming effort.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Office
        Sharing</b>&#8221; means the use of portions of the Premises by Clients and Business Partners, if, with respect to such Clients and Business Partners, such use is in connection with the services being provided to Tenant by the applicable Clients and
      Business Partners, the services being provided to the applicable Clients and Business Partners by Tenant, or the services being jointly provided by Tenant and the applicable Clients and Business Partners.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Transfer</b>&#8221;
      means any assignment, pledge, mortgage, charge, debenture (floating or otherwise), hypothecation, encumbrance, lien attaching to, collateral assignment, or other transfer of this Lease or the leasehold created hereby, or any sublet or other transfer
      of any portion of the Premises, or any Interest Transfer (as defined below), in any case whether voluntarily, by operation of law, or otherwise, or permitting the Premises to be used or occupied by anyone other than Tenant.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">25</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Transferee</b>&#8221;
      means the party to which a Transfer is made.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; &#8220;<b>Interest


        Transfer</b>&#8221; means if Tenant is a corporation, trust, partnership, limited liability company or other entity, (i) the transfer of a Controlling Interest or a majority of the voting stock, beneficial interest, partnership interests, membership
      interests or other ownership interests therein (whether at one time or in the aggregate) or (ii) the sale, mortgage, hypothecation, or pledge of more than 50% of Tenant&#8217;s net assets. A &#8220;<b>Controlling Interest</b>&#8221; means the effective control over
      the management of such entity.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Consent Requests</u>.
      If Tenant desires to effect a Transfer and such Transfer requires Landlord&#8217;s consent, then Tenant shall give to Landlord Notice thereof at least thirty (30) days, but not more than sixty (60) days, prior to the proposed effective date of the
      Transfer, which Notice shall include (a) the name and address of the proposed Transferee, (b) the relevant terms of the Transfer, (c) copies of financial reports and other relevant financial information for the proposed Transferee, (d) information
      regarding the nature of the business the proposed Transferee intends to operate in the Premises and how long the proposed Transferee has operated such business, (e) a fully executed copy of the proposed assignment, sublease, or other document to be
      used to effect the Transfer (the &#8220;<b>Transfer Document</b>&#8221;), and (f) payment to Landlord of One Thousand and No/100 Dollars ($1,000.00) as a transfer review fee. In addition, Tenant shall reimburse Landlord for any third-party expenses reasonably
      incurred by Landlord in connection with the review, inspection, and coordination of Tenant&#8217;s request for Landlord&#8217;s consent to a Transfer, not to exceed $5,000 per request (which amount shall be increased by the same percentage as the Index as of
      each Adjustment Date). Landlord shall not unreasonably withhold, condition or delay its consent to a Transfer. If Landlord&#8217;s consent is required with respect to a Transfer, and Landlord fails to respond to Tenant&#8217;s request for consent within thirty
      (30) days of Tenant&#8217;s request and submission of the documents required by this Section 5.1.2, Tenant may send a second written request, which request shall contain, in bold, capital letters, the following: &#8220;THIS NOTICE CONSTITUTES TENANT&#8217;S SECOND
      NOTICE OF ITS REQUEST FOR CONSENT TO A TRANSFER PURSUANT TO SECTION 5.1.2 OF THE LEASE; LANDLORD&#8217;S FAILURE TO RESPOND TO THIS NOTICE WITHIN FIVE (5) BUSINESS DAYS SHALL BE DEEMED LANDLORD&#8217;S CONSENT TO THE REQUESTED TRANSFER.&#8221; If Landlord fails to
      respond to such second notice within five (5) business days of receipt, Tenant&#8217;s request for the applicable Transfer shall be deemed approved. Tenant hereby waives the provisions of Section 1995.310 of the California Civil Code, or any similar or
      successor laws, now or hereinafter in effect, and all other remedies, including, without limitation, any right at law or in equity to terminate this Lease, on its own behalf and, to the extent permitted under all Applicable Laws, on behalf of the
      proposed transferee.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Permitted Transfer</u>.
      Notwithstanding anything in this <u>Article 5</u> to the contrary, Tenant may assign its interest in this Lease or sublease all or any part of the Premises (each a &#8220;<b>Permitted Transfer</b>&#8221;) to a Permitted Transferee (defined below) with notice to
      Landlord (delivered prior to the Transfer, or in the event Tenant is prohibited from doing so by Applicable Laws or contractual obligations, then as soon as reasonably practical) but without Landlord&#8217;s prior written consent; provided, that (i) with
      respect to a Permitted Transfer involving an assignment of this Lease, the Permitted Transferee assumes this Lease by a written assumption agreement delivered to Landlord prior to the effective date of such Permitted Transfer (unless such prior
      delivery is prohibited by Applicable Laws, in which event Tenant shall deliver such assumption agreement as soon as allowed), (ii) the Permitted Transferee shall use the Premises only for the Permitted Use, (iii) the use of the Premises by the
      Permitted Transferee shall not violate any other agreements or leases affecting the Property, (iv) the occurrence of a Permitted Transfer shall not waive Landlord&#8217;s rights as to any subsequent Transfer, (v) the Permitted Transferee shall satisfy the
      Credit Requirement (defined below), and (vi) Tenant shall have given Landlord written notice at least thirty (30) day before such Transfer (unless such notice is prohibited by applicable Law, in which event Tenant shall give such notice within ten
      days following such Transfer). As used herein, (A) &#8220;<b>Affiliate</b>&#8221; means any person or entity who or which controls, is controlled by, or is under common control with Tenant, (ii) a corporation or other entity which shall be a wholly owned
      subsidiary of the Tenant, (iii) the parent corporation or other entity that wholly owns Tenant, or (iv) a subsidiary of such parent corporation or other entity that wholly owns Tenant, or a corporation or other entity having a majority of its
      ownership in common with the ownership of Tenant, or (v) a Successor corporation, limited liability company or other entity; (B) &#8220;<b>Successor</b>&#8221; means any (i) business entity in which or with which Tenant is merged or consolidated in accordance
      with applicable statutory provisions governing merger and consolidation of business entities, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor, or (ii) the successor or surviving corporation or other entity in the event
      of a merger or consolidation of the Tenant with another corporation, so long as Tenant&#8217;s obligations under this Lease are assumed by the Successor; (C) &#8220;<b>Purchaser</b>&#8221; means any person or entity who or which acquires all or substantially all of
      the assets or equity interests of Tenant; (D) &#8220;<b>Permitted Transferee</b>&#8221; means an Affiliate, Successor or Purchaser. The &#8220;<b>Credit Requirement</b>&#8221; shall be deemed satisfied if, as of the effective date of the Permitted Transfer, the resulting
      tenant under this Lease meets or exceeds all of following minimum criteria immediately following the Transfer: (i) cash on hand equal to at least Two Billion Dollars ($2,000,000,000) according to the Permitted Transferee&#8217;s most recent financial
      statement, determined in accordance with generally accepted accounting principles (&#8220;<b>GAAP</b>&#8221;), (ii) outstanding debt of not more than sixty (60%) of the Permitted Transferee&#8217;s available cash on hand (as determined pursuant to the foregoing
      subsection (i) according to the Permitted Transferee&#8217;s most recent financial statement, determined in accordance with GAAP, and (iii) a market capitalization equal to at least Five Billion Three Hundred Million Dollars ($5,300,000,000).</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">26</font></div>
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.2</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Other Permitted Transfers</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Office Sharing</u>.
      Notwithstanding anything in this <u>Article 5</u> to the contrary, provided no Event of Default has occurred and is continuing, Tenant may, without Landlord&#8217;s consent but upon at least ten (10) days&#8217; prior notice to Landlord, permit up to ten
      percent (10%) of the total leasable area of the Premises to be used for Office Sharing by Clients and Business Partners, without the same constituting a Transfer. Tenant agrees to notify Landlord, promptly upon Landlord&#8217;s written request therefor, as
      to the approximate amount of Office Sharing by Clients and Business Partners and to certify to Landlord that such use or occupancy constitutes Office Sharing by Clients and Business Partners and does not constitute a sublease, assignment or other
      leasehold interest. Notwithstanding the foregoing, Tenant shall not have the right to engage in Office Sharing with respect to any particular Clients and Business Partners as aforesaid if such Clients and Business Partners are engaged in a business,
      or the Premises will be used in a manner, that is inconsistent with the Permitted Use. For purposes of this Lease, the acts or omissions of the employees or other personnel of Clients and Business Partners shall be deemed to be the acts or omissions
      (as applicable) of Tenant. Upon Landlord&#8217;s request, Clients and Business Partners who are Office Sharing shall provide to Landlord satisfactory evidence of insurance covering their activities within the Premises.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">27</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Transfers</u>.
      For so long as Tenant is a corporation whose ownership equity is available through the free trade of shares of stock on nationally recognized stock exchanges or over-the-counter (OTC) markets that are subject to the oversight of the United States
      Securities and Exchange Commission (a &#8220;<b>Public Company</b>&#8221;), any transfer of Tenant&#8217;s equity interests (or those of its Affiliates) whatsoever shall not be deemed a Transfer under this Lease and, for the avoidance of doubt, shall not require
      Landlord&#8217;s consent.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Conditions to
        Effectiveness</u>. As conditions precedent to any Transfer becoming effective and binding on Landlord:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.4.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; except as otherwise
      specified herein, prior to the proposed effective date of the Transfer, Tenant shall give to Landlord a copy of the fully executed Transfer Document, which shall (i) be in form and substance reasonably acceptable to Landlord, and (ii) for an
      assignment of this Lease, contain Transferee&#8217;s express assumption of Tenant&#8217;s obligations under this Lease and waivers by Tenant, for the benefit of Landlord, of all applicable suretyship defenses (unless such prior delivery is prohibited by
      Applicable Laws, in which event Tenant shall deliver such documents as soon as allowed); and</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.4.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; as of the proposed
      effective date of the Transfer, there shall exist no Event of Default.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Miscellaneous</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; Notwithstanding any
      Transfer, permitted or otherwise, including without limitation a Permitted Transfer, (a) Tenant shall not be released and shall at all times remain directly, primarily, and fully responsible and liable for the payment of Rent and for compliance with
      all of the other obligations to be performed by Tenant under the terms, provisions and covenants of this Lease, and (b) if any Transferee defaults under this Lease, then Landlord may proceed directly against Tenant without the necessity of exhausting
      remedies against such Transferee. Notwithstanding the foregoing, Tenant shall be automatically released from all liability under the Lease accruing from and after the date of a Transfer if the Transfer is a Permitted Transfer that is a merger or
      consolidation whereby the named Tenant herein is not the surviving entity; provided, however, as conditions of the foregoing release: (i) the surviving entity shall assume, either expressly or by operation of law, all of the obligations of the
      preceding entity for liabilities accruing before and after the Transfer, and (ii) the surviving entity must retain ownership of substantially all of the assets of the preceding entity.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">28</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; Upon the occurrence of
      an Event of Default, if all or any portion of the Premises is then subject to one or more subleases, then Landlord, in addition to any other remedies provided in this Lease or at law or in equity, may collect directly from the subtenants under such
      subleases all rents due and becoming due to Tenant or a Transferee under such subleases and apply such rent against any sums due to Landlord from Tenant under this Lease, and no such collection shall be construed to constitute a novation or release
      of Tenant from the further performance of Tenant&#8217;s obligations under this Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except for any
      Permitted Transfer, if the proposed Transfer is an assignment or a sublease of more than seventy five percent (75%) of the Premises for a term longer than seventy five percent (75%) of the then remaining Term, then Landlord shall have the right in
      its sole and absolute discretion to terminate this Lease by sending Tenant written notice of such termination within thirty (30) days after Landlord's receipt of Tenant's notice requesting consent to the Transfer. If Landlord elects to terminate this
      Lease, Tenant may withdraw its notice requesting consent to the Transfer by providing written notice within five (5) business days after Landlord&#8217;s termination (with time being of the essence), in which case Landlord&#8217;s termination shall be negated,
      and the Lease shall continue pursuant to its terms. If Landlord elects to terminate this Lease, then Tenant shall tender the Premises to Landlord in the condition required by this Lease at the end of the Term, and this Lease shall terminate, on the
      proposed effective date of the requested Transfer, and Tenant shall have no further obligations under this Lease except for those accruing prior to the termination date and those that, pursuant to the terms of the Lease, survive the expiration or
      early termination of the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except for a Permitted
      Transfer, in the event, if any, that (i) all rent and other consideration that Tenant receives as a result of a Transfer exceeds (ii) the Rent payable to Landlord for the portion of the Premises and Term covered by the Transfer (allocated on a per
      square foot basis), then Tenant shall, at Landlord&#8217;s election, pay to Landlord an amount equal to fifty percent (50%) of such excess, from time to time on a monthly basis upon Tenant&#8217;s receipt of such excess; provided that in determining any such
      excess, Tenant may deduct from the excess all reasonable and customary expenses directly incurred by Tenant in connection with such Transfer, except that any construction costs incurred by Tenant in connection with such Transfer shall be deducted on
      a straight-line basis over the term of the applicable Transfer. If Tenant is in Default, Landlord may require that all sublease payments be made directly to Landlord, in which case Tenant shall receive a credit against Rent in the amount of Tenant&#8217;s
      share of payments received by Landlord.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.5&#160;&#160;&#160;&#160;&#160;&#160;&#160; Without limiting
      Landlord&#8217;s right to withhold its consent to any transfer by Tenant, and regardless of whether Landlord shall have consented to any such transfer, neither Tenant nor any other person having an interest in the possession, use or occupancy of the
      Premises or any part thereof shall enter into any lease, sublease, license, concession, assignment or other transfer or agreement for possession, use or occupancy of all or any portion of the Premises that provides for rent or other payment for such
      use, occupancy or utilization based, in whole or in part, on the net income or profits derived by any person or entity from the space so leased, used or occupied, and any such purported lease, sublease, license, concession, assignment or other
      transfer or agreement shall be absolutely void and ineffective as a conveyance of any right or interest in the possession, use or occupancy of all or any part of the Premises..</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">29</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">5.5.6&#160;&#160;&#160;&#160;&#160;&#160;&#160; This Section 5.5 shall
      survive the expiration or earlier termination of this Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article



      6<br>
      INDEMNIFICATION; rELEASE; INSURANCE</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.1</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Indemnification and Release</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the extent permitted
      by Applicable Law, Tenant shall protect, indemnify, release, defend and hold Landlord (and the Landlord Parties) harmless from and against any and all Claims to the extent caused by or incurred by reason of: (a) any damage to any property (including
      the property of Landlord), or any injury (including death) to any person, occurring in, on, or about any portion of the Premises, except to the extent caused by or arising from the gross negligence or willful misconduct of Landlord or the Landlord
      Parties; (b) any Alterations, work, or other thing done by Tenant or any Tenant Parties in or about any portion of the Premises, or from transactions of Tenant concerning any portion of the Premises; (c) Tenant&#8217;s failure to comply with any Applicable
      Laws; (d) any breach or default by Tenant of any representation, covenant or other term of this Lease; provided that Tenant shall not be obligated to so indemnify Landlord to the extent any such matter arises from, or is caused by, the willful
      misconduct or gross negligence of Landlord or the Landlord Parties; or (e) Tenant&#8217;s use and occupancy of the Premises. Tenant&#8217;s agreement to indemnify, defend and hold the Landlord and the Landlord Parties (the &#8220;<b>Indemnitees</b>&#8221;) harmless is
      conditioned upon the Indemnitees (i) providing written notice to Tenant of any claim, demand or action arising out of the indemnified activities within thirty (30) days after Landlord has actual knowledge of such claim, demand or action, provided
      that the failure to so notify Tenant will not relieve Tenant of its obligations hereunder except to the extent such failure has actually materially prejudiced Tenant; (ii) permitting Tenant to assume full responsibility to investigate, prepare for
      and defend against any such claim or demand, subject to Landlord&#8217;s reasonable approval of any counsel used in the defense of such claim or demand; (iii) assisting Tenant, at Tenant&#8217;s expense, in the reasonable investigation of, preparation of and
      defense of any such claim or demand; and (iv) not settling such claim or demand that would result in a payment in excess of $100,000 (individually or in the aggregate) without Tenants&#8217; prior written consent, which shall not be unreasonably withheld,
      conditioned, or delayed. &#8220;<b>Claims</b>&#8221; mean claims, demands, losses, penalties, fines, liabilities, actions (including informal proceedings), settlements, judgments, damages, reasonable costs, and reasonable expenses (including reasonable
      attorneys&#8217; fees and consultants&#8217; fees, court costs, and other litigation expenses) of whatever kind or nature, known or unknown, contingent or otherwise, incurred or suffered by, or asserted against, the party in question.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; Tenant hereby releases
      Landlord and the Landlord Parties from any and all liability for any loss or claim, including all economic losses and all consequential and indirect losses, as a result of loss, damage or injury to the property and persons of Tenant and its
      employees, as a result of any occurrence in, upon or at the Premises or the occupancy or use by the Tenant of the Premises, including damage to the Building or loss of access to the Premises, whether or not such loss or claim may have arisen out of
      the acts, omissions or negligence of Landlord, the Landlord Parties or those for whom Landlord or the Landlord Parties are in law responsible. Except with respect to Sections 1.3 and 3.3.4, Landlord hereby releases Tenant from any and all liability
      for consequential or special damages, including lost profits (which shall not limit the rights and remedies of Landlord expressly provided in this Lease).</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">30</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0.5in"></td>
        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>Insurance</u>.</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Landlord&#8217;s
        Insurance</u>. Landlord shall obtain and keep in force throughout the Term the following coverages in the following amounts: (a) commercial general liability insurance on an &#8220;occurrence&#8221; basis on the current ISO CG 00 01 occurrence form or its
      equivalent with a deductible reasonably acceptable to Landlord with a limit of not less than $5,000,000 per occurrence, (b) property damage insurance covering the core and shell of the Buildings and structural elements of other improvements situated
      upon the Premises on a replacement cost basis against loss or damage as provided by the standard fire and extended coverage policy, including, without limitation, earthquake and terrorism, and all other risks of direct physical loss as insured
      against under a special extended coverage endorsement in amounts and with a deductible determined by Landlord in its commercially reasonable discretion, (c) boiler and machinery insurance on a repair or replace basis, (d) business interruption
      insurance with respect to insurance required under (b) and (c) above with an indemnity period determined by Landlord, and (e) any such other insurance as Landlord&#8217;s lender may require. Tenant shall provide Landlord with such information from time to
      time as Landlord may reasonably require in connection with Landlord&#8217;s determination of the insurance required pursuant to clause (b), above.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Tenant&#8217;s Insurance.</u>
      Tenant shall procure and maintain during the Lease Term, at its sole cost and expense, a policy or policies of insurance protecting Landlord and Tenant against each of the following:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Commercial
      general liability insurance with respect to the operations of Tenant insuring against bodily injury or death and property damage in amounts (i) not less than $10,000,000 in the aggregate,(ii) not less than $2,000,000 per occurrence and (iii) not less
      than $10,000,000 of excess umbrella liability insurance. Such insurance shall contain separation of insured clauses and separation of insureds, with Landlord and any third party now or hereafter providing financing to Landlord where such third party
      has a security interest in the Premises under such financing shall be included as additional insureds. Tenant may satisfy the foregoing limits through any combination of primary and umbrella/excess policies, provided the combined total coverage is
      not less than $20,000,000 in the aggregate. The amount of such commercial general liability insurance shall be increased from time to time as Landlord may reasonably determine. All such bodily injury and property damage insurance shall insure
      Tenant&#8217;s exposure with respect to the indemnity agreement as to personal injury or property damage contained in Section 6.1 herein.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">31</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Insurance
      covering Tenant&#8217;s construction, alterations, additions or improvements permitted herein (other than the core and shell of the Buildings and structural elements of other improvements), existing tenant improvements, trade fixtures and personal
      property, in an amount not less than 100% of their full replacement cost from time to time during the Lease Term, providing protection on an all risk basis, including, without limitation, coverage for earthquakes, for the repair or replacement of the
      property damaged or destroyed.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Pollution
      Legal Liability that provides first party coverage for clean-up costs and third party coverage for bodily injury and property damage resulting from pre-existing and future contamination conditions, of at least Five Million Dollars ($5,000,000.00) per
      pollution event; such coverage shall specifically include this lease as an insured contract.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; The minimum
      limits of insurance required to be carried by Tenant shall not limit Tenant&#8217;s liability. All policies of insurance to be provided by Tenant shall be issued by insurance companies, with general policy holder's rating of not less than A and a financial
      rating of not less than Class VIII as rated in the most current available "Best's" Insurance Reports, and admitted to do business in the State of California. Such policies shall be issued in the name of Tenant, with Landlord, Landlord&#8217;s managing
      agent, lenders, and any other party designated by Landlord (&#8220;<b>Additional Insured Parties</b>&#8221;) included as an additional insured. Tenant&#8217;s property insurance and any builder&#8217;s risk policy carried by Tenant or its contractors shall identify Landlord
      or, at Landlord&#8217;s direction, Landlord&#8217;s lender, as a loss payee. The full replacement cost of improvements under Tenant&#8217;s property insurance may be designated by Landlord in the good faith exercise of Landlord's judgment. In the event that Tenant
      does not agree with Landlord's designation, Tenant shall have the right to submit the matter to an insurance appraiser reasonably selected by Landlord and paid for by Tenant. The insurance appraiser shall submit a written report of his appraisal, and
      if said report discloses that the improvements are not insured as therein required, Tenant shall promptly obtain the insurance required. The policies provided by Tenant shall be for the mutual and joint benefit and protection of Landlord and Tenant,
      and certificates of insurance shall be delivered to the Landlord within ten (10) days after the Lease Commencement Date and, thereafter, within thirty (30) days after to the expiration of the term of each such policy. Upon Landlord&#8217;s request, Tenant
      shall deliver to Landlord, in lieu of such certificates, copies of the policies of insurance required to be carried under Section 6.2.2 showing that the Additional Insured Parties are named as additional insureds (with respect to the applicable
      policies). Upon the expiration or termination of any such policy, renewal or additional policies shall be procured and maintained by the Tenant to provide the required coverage. All policies of insurance delivered to Landlord must contain a provision
      that the company writing said policy will provide Landlord with thirty (30) days&#8217; notice in writing in advance of any cancellation or lapse or the effective date of any reduction in the amounts of insurance (except in the event of non-payment of
      premium, in which case ten (10) days&#8217; written notice shall be given). Notwithstanding the foregoing, if the foregoing requirement that the insurance company provide prior notice to Landlord of cancellation or material change of the applicable policy
      cannot reasonably be obtained based on then-prevailing insurance industry practices, Tenant shall so advise Landlord of such unavailability and shall instead shall use reasonable efforts to cause its insurer to provide Landlord, and in any event
      Tenant shall provide Landlord with, notice of any such cancellation of any of Tenant&#8217;s insurance policies. All of Tenant&#8217;s commercial general liability, property damage and other casualty policies shall be written as primary policies, not
      contributing with and not in excess of coverage which Landlord may carry. Tenant agrees that if, after the Commencement Date, Tenant does not take out and maintain the insurance required under this Section 6.2, Landlord may (but shall not be required
      to) procure, and thereafter maintain, said insurance on Tenant's behalf, and any costs or expenses incurred by Landlord in connection therewith, plus an administration fee of ten percent (10%) of the cost, shall promptly be paid by Tenant to Landlord
      as Additional Rent.</font></p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">32</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;
      Notwithstanding anything to the contrary, Tenant's obligation to carry the insurance described in this Section 6.2.2 may be brought within the coverage of a so-called blanket policy or policies of insurance carried and maintained by the Tenant,
      provided that (i) Landlord will be an additional insured thereunder as its interests may appear; (ii) the coverage afforded Landlord will not be reduced or diminished by reason of the use of such blanket policy of insurance; and (iii) the
      requirements set forth herein are otherwise satisfied. In the event of any Claims covered by Tenant&#8217;s insurance, Tenant shall, within 10 days following Landlord&#8217;s written request, provide Tenant with copies of the applicable insurance policies
      carried by Tenant pursuant to this Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Release of
        Subrogation Rights</u>. Tenant and Landlord each hereby releases the other from liability and waives all right to recover against the other for any loss from perils insured against under their property insurance policies, including any extended
      coverage and special form endorsements to said policies; provided, however, this <u>Section 6.2.3</u> shall be inapplicable if it would have the effect, but only to the extent that it would have the effect of invalidating any insurance coverage of
      Landlord or Tenant. Tenant and Landlord&#8217;s property damage policies shall contain, if available, a waiver of subrogation clause.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">6.2.4&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Insurance for
        Alterations</u>. During the performance of any Alterations by Tenant, (a) the insurance required under this <u>Section 6.2</u> shall extend to all of Tenant&#8217;s consultants and contractors (and subcontractors of any tier) and shall include injuries
      to persons and damage to property arising in connection with such Alterations and (b) Tenant shall also maintain such other insurance as Landlord may reasonably require, including all-risk builder&#8217;s insurance, each of which policies shall name
      Landlord and Landlord&#8217;s lender as additional insureds and loss payees. Tenant shall give to Landlord copies of the policies of such insurance prior to commencing construction of such Alterations.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article



      7<br>
      THIRD PARTIES</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-transform: uppercase; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Subordination,
        Attornment and Non-Disturbance</u>. This Lease shall be automatically subject and subordinate at all times to the lien of any first priority mortgages or deeds of trust on, against, or affecting any portion of the Premises, or Landlord&#8217;s interest
      or estate in any portion of the Premises, and to all renewals, modifications, consolidations, replacements, and extensions thereof (each, a &#8220;<b>Mortgage</b>&#8221;); provided that, as a condition precedent to such subordination, Tenant must receive a fully
      executed subordination, non-disturbance and attornment agreement substantially in the form attached as Exhibit E hereto, or in such other commercially reasonable form as required by Landlord&#8217;s Mortgagee (as hereinafter defined) (a &#8220;<b>SNDA</b>&#8221;) from
      any current and future encumbrance holder (each, a &#8220;<b>Mortgagee</b>&#8221;) with such changes as reasonably requested by Tenant. Landlord shall request a SNDA from each present and any future Mortgagee seeking to subordinate this Lease to the lien of its
      Mortgage and deliver the same to Tenant. In the event Mortgagee enforces it rights under the Mortgage, Tenant, at Mortgagee&#8217;s option, will attorn to Mortgagee or its successor; provided, however, that, subject to the terms of any SNDA between Tenant
      and such Mortgagee (which shall govern in the event of any conflicts with the provisions of this Section 7.1), Mortgagee or its successor shall not be liable for or bound by (i) any payment of any Rent installment that may have been made more than
      thirty (30) days before the due date of such installment, (ii) any act or omission of or default by Landlord under this Lease (but Mortgagee, or such successor, shall be subject to the continuing obligations of landlord under the Lease arising from
      and after such succession, but only to the extent of Mortgagee&#8217;s, or such successor&#8217;s, interest in the Premises as provided in Article 12), (iii) any then-exercisable credits, claims, setoffs or defenses that Tenant may have against Landlord, or (iv)
      any obligation to provide tenant improvements allowances or perform tenant improvements to be provided by Landlord hereunder.</font></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Mortgagee&#8217;s Right
        to Cure</u>. Notwithstanding anything to the contrary in this Lease, before exercising any right (a) of offset, counterclaim, reduction, deduction, or abatement against Tenant&#8217;s payment of Rent under this Lease or (b) to terminate the Lease or to
      claim a partial or total eviction, in each case arising from Landlord&#8217;s default under this Lease, (i) Tenant shall provide to each Mortgagee whose name and address has been furnished in writing to Tenant with written notice of the default by Landlord
      giving rise to same, and (ii) Mortgagee shall have a period of thirty (30) days after the last date on which Landlord could have cured such default within which such Mortgagee will be permitted, but not be obligated, to cure such default. If such
      default cannot be cured within such thirty-(30)-day period, then such Mortgagee shall have such additional time as may be necessary to cure such default, if prior to the end of such thirty-(30)-day period such Mortgagee has commenced and is
      diligently pursuing such cure or the remedies under the Mortgage necessary for Mortgagee to be able to effect such cure, in which event Tenant shall have no right with respect to such default while such cure and remedies are being diligently pursued
      by such Mortgagee. Notwithstanding the foregoing, such Mortgagee shall have no obligation to cure (and shall have no liability or obligation for not curing) any default by Landlord. In addition, as to any default by Landlord the cure of which
      requires possession and control of the Premises, provided that such Mortgagee undertakes by written notice to Tenant to exercise reasonable efforts to cure or cause to be cured by a receiver such default within the period permitted by this <u>Section


        7.2</u>, such Mortgagee&#8217;s cure period shall continue for such additional time as such Mortgagee may reasonably require to either: (A) obtain possession and control of the Premises with due diligence and thereafter cure the default with reasonable
      diligence and continuity; or (B) obtain the appointment of a receiver and give such receiver a reasonable period of time in which to cure the default.</font></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: justify; text-indent: 0.5in"></p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Sale of the Premises</u>.</font>
    Subject to the provisions of Article 11, if Landlord sells or conveys the Premises, such sale or conveyance shall release Landlord from any liability from and after such sale or conveyance upon any of the covenants or conditions, expressed or implied,
    contained in this Lease in favor of Tenant (to the extent such liability is expressly assumed by such transferee), and in such event, Tenant agrees to look solely to the successor-in-interest of Landlord in and to this Lease with respect to such
    liabilities that are incurred from and after such sale or conveyance. In the event Landlord enters into a purchase and sale agreement for the sale or conveyance of the Premises, in the event such purchaser is an entity engaged primarily in the business
    of research, development, manufacturing, sale, or marketing of a biopharmaceutical product (a &#8220;<b>Pharma Competitor</b>&#8221;), then the Pharma Competitor shall execute a non-disclosure and confidentiality agreement substantially in the form attached hereto
    as <u>Exhibit F</u>; provided, however, that Tenant shall negotiate in good faith in the event the Pharma Competitor wishes to deviate from the form attached as <u>Exhibit F</u>. Except as set forth in this <u>Section 7.3</u>, this Lease shall not
    be affected by any such sale or conveyance and Tenant agrees to attorn to the purchaser or assignee. Landlord shall transfer or deliver the Security Deposit to Landlord&#8217;s successor-in-interest and thereupon Landlord shall be discharged from any further
    liability with regard thereto.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Estoppel Certificates</u>.</font>
    Within ten (10) business days after Landlord&#8217;s written request, Tenant shall execute and deliver to Landlord and any of Landlord&#8217;s then existing or prospective lenders, investors, or purchasers of any portion of the Premises, a certificate
    substantially in the form attached as <u>Exhibit C</u>, or in such other commercially reasonable form and containing such other information as Landlord or any such lenders, investors, or purchasers, may reasonably require. Any certificate delivered in
    accordance with this <u>Section 7.4</u> may be relied upon by any such lender, investor, or purchaser. Within ten (10) business days after Tenant&#8217;s request, Landlord shall execute and deliver to Tenant and any of Tenant&#8217;s then existing or prospective
    lenders, investors, or purchasers, a statement in writing certifying that Tenant is in possession of the Premises under the terms of this Lease, that this Lease is unmodified and in full force and effect (or, if there have been modifications, that this
    Lease is in full force and effect, as modified, and setting forth such modifications), stating the dates to which rent has been paid, and either stating that no defaults exist hereunder, or specifying each such default of which Landlord may have
    knowledge, and such other matters as may be reasonably requested by Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">7.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Liens</u>.</font> Tenant shall,
    within fifteen (15) business days of written notice of filing, discharge (either by payment or by filing of the necessary bond, insure over, or otherwise) any mechanic&#8217;s, materialman&#8217;s or other lien or encumbrance against any portion of the Premises
    that arises out of any payment due for, or purported to be due for, any labor, services, materials, supplies or equipment alleged to have been furnished to or for Tenant. If Tenant shall fail to so discharge such lien or encumbrance (either by payment
    or by filing of the necessary bond, insure over or otherwise) then, such failure shall be an Event of Default under this Lease and, in addition to any other right or remedy of Landlord, Landlord may discharge the same (either by payment or by filing of
    the necessary bond or otherwise), and any payment, costs and expenses incurred by Landlord in connection therewith, including reasonable attorneys&#8217; fees, shall be repaid together with interest thereon at the rate set forth in <u>Section 2.3</u> from
    the date of payment. Notwithstanding the foregoing or anything to the contrary in this Lease, Tenant may contest any lien (and Landlord shall not discharge such lien at Tenant&#8217;s expense for so long as Tenant is diligently pursuing such contest) if (i)
    such lien is the subject of a bona fide dispute in which Tenant is contesting the amount or validity thereof, (ii) Tenant notifies Landlord in writing of such dispute, (iii) Tenant has or establishes unrestricted cash reserves to in an amount equal to
    125% of (x) the amount of Tenant&#8217;s obligations being contested plus (y) any additional interest, charge or penalty arising from such contested lien and (iv) such lien is fully bonded by Tenant to the reasonable satisfaction of Landlord and any
    Mortgagee.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article 8<br>
      EVENTS OF DEFAULT &amp; REMEDIES</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0.5in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Events of Default</u>.</font> &#8220;<b>Event


      of Default</b>&#8221; means any of the following:</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant fails to pay
      when due any Rent, and such failure continues for five (5) business days after Landlord delivers to Tenant notice thereof; provided, however, Landlord shall not be required to provide prior notice of Tenant&#8217;s failure to pay any recurring obligation
      to pay any Base Rent or any monthly payment of estimated Taxes or Insurance Expenses more than twice during any twelve (12) month period, after which Tenant&#8217;s failure to pay such amount shall be an Event of Default if Tenant fails to pay the amount
      when due and such failure continues for five (5) business days after the due date;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;except as otherwise
      provided in this Lease, Tenant fails to comply with any term, provision, or covenant of this Lease and such failure continues for thirty (30) days after Landlord gives to Tenant Notice thereof (but if such failure is curable but cannot reasonably be
      cured during such 30-day period, and if Tenant has commenced such cure promptly and in any case within such 30-day period and thereafter has diligently pursued such cure to completion, then such 30-day period shall be extended to ninety (90) days);</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant fails to obtain
      and keep in force at all times any insurance required under this Lease, and such failure continues for five (5) days after Landlord gives to Tenant Notice thereof;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant fails to
      deliver to Landlord, within fifteen (15) business days after Landlord gives Tenant Notice thereof, any instrument or assurance required under this Lease;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.25in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;The filing by Tenant
      in any court pursuant to any statute or petition in bankruptcy or insolvency or for reorganization or arrangement for the appointment of a receiver or all of a portion of Tenant&#8217;s property the filing against Tenant of any such petition, or the
      commencement of a proceeding for the appointment of a trustee, receiver or liquidator for Tenant, or of any property of Tenant, or a proceeding by any governmental authority for the dissolution or liquidation of Tenant, if such proceeding shall not
      be dismissed or trusteeship discontinued within sixty (60) days of commencement of such proceeding or the appointment of such trustee or receiver; or the making by Tenant of an assignment for the benefit of creditors. Tenant hereby stipulates to the
      lifting of the automatic stay in effect and relief from such stay for Landlord in the event Tenant files a petition under the United States Bankruptcy Laws, for the purpose of landlord pursuing its rights and remedies against Tenant;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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      cause to be released any mechanics liens filed against the Premises within twenty (20) days after the date Tenant is notified that the same shall have been filed or recorded, subject to Tenant&#8217;s right to dispute liens as set forth in <u>Section 7.5</u>;
    </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Abandonment of the
      Premises pursuant to California Civil Code Section 1951.3, or failure by Tenant or a transferee permitted pursuant to Article 5 to occupy at least sixty percent (60%) of the Premises for a period of ninety (90) consecutive days or more for any reason
      other than restoration following a casualty or condemnation, Force Majeure affecting Tenant&#8217;s ability to operate within the Premises, and temporary cessations in order to complete Alterations in accordance with this Lease, provided that it shall not
      be deemed to be a failure to occupy for purposes of this clause (ii) if the applicable portion of the Premises remains fully furnished with the necessary equipment to conduct business operations consistent with the Permitted Use as it was undertaken
      prior to such failure to occupy, with regular repair, maintenance, and cleaning occurring in accordance with the terms of this Lease, no other Event of Default has occurred, and Tenant is actively marketing the applicable portion of the Premises for
      sublease (or marketing this Lease for assignment); </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant&#8217;s failure to
      provide a SNDA within the period required by Section 7.1 or Tenant&#8217;s failure to provide a certificate within the time period required by Section 7.4 and such failure continues for five (5) business days after Landlord delivers to Tenant notice
      thereof; </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant performs a
      Transfer in violation of Article 5, or</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(j)&#160;&#160;&#160;&#160;&#160;&#160;&#160;If Landlord elects, in
      its sole discretion, the occurrence of any &#8220;Event of Default&#8221; under the Companion Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Remedies</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.65"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Upon Event of Default</u>.</font> Upon the occurrence
    of any Event of Default, Landlord shall have the option to pursue any one or more of the following remedies without any Notice or demand whatsoever (except as expressly provided herein), concurrently or consecutively and not alternatively (in addition
    to any other remedies available to Landlord at law or in equity), all of which remedies shall be distinct, separate and cumulative:</p>
  <div style="clear: both; margin-top: 11pt; margin-bottom: 11pt;" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">37</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Termination</u></font>.
    Landlord may terminate this Lease upon notice to Tenant, in which event Tenant shall vacate the Premises immediately and deliver possession of the Premises to Landlord in the condition which Tenant is required to surrender the Premises at the
    expiration of the Term (Tenant hereby waives, relinquishes and releases for itself and for all those claiming under Tenant any right of occupancy of the Premises following termination of this Lease, and any right to redeem or reinstate this Lease by
    order or judgment of any court or by any legal process or writ under Applicable Laws, including, without limitation, California Code of Civil Procedure Sections 473 and 1179, and California Civil Code Section 3275), and if Tenant fails to do so, then
    Landlord may, after due process of law, enter upon and take possession of the Premises, and expel or remove Tenant and any other person who may be occupying the Premises or any portion thereof, without being liable for prosecution or any claim or
    damages therefor. Upon termination of the Lease as provided in this Section, Landlord may recover from Tenant the following: (i) the worth at the time of award of any unpaid rent which has been earned at the time of such termination; plus (ii) the
    worth at the time of award of the amount by which the unpaid rent which would have been earned after termination until the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iii) the worth
    at the time of award of the amount by which the unpaid rent for the balance of the Term after the time of award exceeds the amount of such rental loss that Tenant proves could have been reasonably avoided; plus (iv) any other amount necessary to
    compensate Landlord for all the detriment proximately caused by Tenant&#8217;s failure to perform its obligations under this Lease or which in the ordinary course of things would be likely to result therefrom, specifically including but not limited to,
    attorneys&#8217; fees, brokerage commissions and advertising expenses incurred, expenses of remodeling the Premises or any portion thereof for a new tenant, whether for the same or a different use, and any special concessions made to obtain a new tenant;
    plus (v) at Landlord&#8217;s election, such other amounts in addition to or in lieu of the foregoing as may be permitted from time to time by Applicable Law. The term &#8220;rent&#8221; as used in this Section 8.2.1(a) shall be deemed to be and to mean all sums of every
    nature required to be paid by Tenant pursuant to the terms of this Lease, whether to Landlord or to others, including, without limitation, late charges and interest. As used in Sections 8.2.1(a)(i) and (ii), the &#8220;worth at the time of award&#8221; shall be
    computed by allowing interest at the rate set forth in Section 2.4 above, but in no case greater than the maximum amount of such interest permitted by Applicable Law. As used in Section 8.2.1(a)(iii), the &#8220;worth at the time of award&#8221; shall be computed
    by discounting such amount at the discount rate of the Federal Reserve Bank of San Francisco at the time of award plus one percent (1%). Landlord shall have no obligation to relet the Premises or any part thereof and shall in no event be liable for
    failure to relet the Premises or any part thereof, or, in the event of any such reletting, for refusal or failure to collect any rent due upon such reletting. No such refusal or failure shall operate to relieve Tenant of any liability under this Lease.
    Tenant shall instead remain liable for all unpaid Rent and for all such expenses. This paragraph is expressly intended to afford Landlord the remedies provided for in California Civil Code &#167; 1951.2.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Possession</u>. </font>Landlord



    may re-enter the Premises without terminating this Lease by Notice to Tenant and sublet the whole or any part thereof for the account of Tenant upon as favorable terms and conditions as the market will allow; <u>provided</u>, <u>however</u>, that
    Tenant shall have not less than thirty (30) days following such re-entry to remove Tenant&#8217;s Personalty from the Premises. In the latter event (a) Landlord shall have the right to collect any Rent which may thereafter become due and payable under such
    sublease and to apply the same first, to the payment of any expenses incurred by Landlord in dispossessing Tenant and in subletting the Premises, and second, to the payment of the Rent herein reserved and to the fulfillment of Tenant&#8217;s other covenants
    hereunder, and (b) Tenant shall be liable for amounts equal to the Rent as the same would under the terms of this Lease become due, less any amounts actually received by Landlord and applied on account of Rent as aforesaid. Landlord shall have the
    remedy described in California Civil Code Section 1951.4 (lessor may continue lease in effect after lessee&#8217;s breach and abandonment and recover rent as it becomes due, if lessee has the right to sublet or assign, subject only to reasonable
    limitations). Accordingly, if Landlord does not elect to terminate this Lease due to any Event of Default, Landlord may, from time to time, without terminating this Lease, enforce all of its rights and remedies under this Lease, including, without
    limitation, the right to recover all Rent as it becomes due.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">38</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Subleases of
        Tenant.</u></font> Whether or not Landlord elects to terminate this Lease, Landlord may terminate any and all subleases or other consensual arrangements for possession or occupancy of the Premises entered into by Tenant or any subtenant of Tenant,
    or may succeed to Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in such subleases or other arrangements. If Landlord elects to succeed to Tenant&#8217;s or Tenant&#8217;s subtenant&#8217;s interest in any such subleases or other arrangements, then as of the date of Notice
    by Landlord of such election (i) Tenant shall have no further right to, or interest in, the rent or other consideration receivable thereunder, and (ii) any sublessee or other occupant of the Premises shall attorn to and recognize Landlord as its
    landlord.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Right to Perform
        Tenant&#8217;s Covenants</u>. If Tenant shall at any time fail to pay any Taxes or to take out, pay for, maintain or deliver any of the insurance provided for in this Lease, or shall fail to make any other payment or perform any obligation under this
      Lease, and such failure continues beyond applicable notice and cure periods (or without any notice and right to cure where required to protect life or property), then Landlord may, without waiving or releasing Tenant from any obligations of Tenant in
      this Lease contained, pay any such Tax, effect any such insurance coverage and pay premiums therefor, and make any other payment or perform any other act which Tenant is obligated to perform under this Lease, in such manner and to such extent as
      Landlord shall, in its sole discretion, deem necessary. In exercising any such rights, Landlord may pay necessary and incidental costs and expenses including reasonable attorneys&#8217; fees. All sums so paid by Landlord and all necessary and incidental
      costs and expenses in connection with the performance of any such act by Landlord, together with interest thereon at the Interest Rate, shall be payable to Landlord on demand. If Landlord incurs any third-party expenses to cure a breach of any
      non-monetary obligation of Tenant, Tenant shall also pay an administrative charge equal to ten percent (10%) of the cost of the work performed by Landlord. Landlord shall have no obligation to perform on Tenant&#8217;s behalf and if Landlord does so,
      Landlord shall not be liable to Tenant for any damage resulting from its actions.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; margin-left: 0.5in; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Other Remedies</u>.</font>
    In addition to the remedies set forth in this Lease, Landlord shall have all other remedies provided by law or statute to the same extent as if fully set forth herein word for word (including, without limitation, the right to enforce Tenant&#8217;s specific
    performance of each and every covenant, condition and other provisions of this Lease). No remedy herein conferred upon, or reserved to Landlord shall exclude any other remedy herein or by law provided, but each shall be cumulative.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">39</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Form of Payment
        Following Event of Default</u>. Following the occurrence of a monetary Event of Default, Landlord shall have the right to require that any or all subsequent amounts paid by Tenant to Landlord under this Lease, whether relating to the Event of
      Default in question or otherwise, be paid in the form of wire transfer or immediately available funds, or by other means approved by Landlord, notwithstanding any prior acceptance by Landlord of payments from Tenant in any different form.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Mitigation of
        Damages</u></font>. Except as required by law, Landlord shall have no obligation to mitigate its damages. If Landlord is required by law to mitigate its damages under this Lease, then (a) Landlord shall be required only to use reasonable efforts to
    so mitigate, which shall not exceed such efforts as commercial landlords generally use to lease similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California; (b) Landlord shall not be deemed to have
    failed to so mitigate if Landlord leases less than all of the Premises; and (c) Landlord&#8217;s failure to so mitigate shall only reduce the Rent to which Landlord is entitled. Tenant acknowledges that Landlord&#8217;s rejection of a prospective replacement
    tenant based on an offer of rentals below published rates for new leases of similar premises in the vicinity of the tri-city area (Oceanside, Carlsbad and Vista) of the State of California at the time in question, or containing terms less favorable
    than those contained herein, shall not give rise to a claim by Tenant that Landlord failed to so mitigate.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Waiver of Right
        of Redemption</u></font>. Tenant (for itself and all others claiming through Tenant) irrevocably waives and releases any rights under any law now or hereafter existing to redeem or reinstate this Lease or Tenant&#8217;s right of occupancy of the Premises
    after termination of this Lease, including, without limitation, any and all rights conferred by Section 3275 of the Civil Code of California and by Sections 1174(c) and 1179 of the Code of Civil Procedure of California..</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Reimbursement of
        Expenses</u></font>. In the case of termination of this Lease pursuant to this Section 8.2, Tenant shall reimburse Landlord for all expenses arising out of such termination, including without limitation, all costs incurred in collecting amounts due
    from Tenant under this Lease (including legal fees, costs of litigation and the like); all expenses incurred by Landlord in attempting to relet the Premises or parts thereof (including advertisements, brokerage commissions, Tenant&#8217;s allowances, costs
    of preparing space, and the like); all of Landlord&#8217;s then unamortized costs of any work allowances provided to Tenant for the Premises; and all Landlord&#8217;s other reasonable expenditures necessitated by the termination. The reimbursement from Tenant
    shall be due and payable immediately from time to time upon notice from Landlord that an expense has been incurred, without regard to whether the expense was incurred before or after the termination.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in; margin-left: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.2.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Claims in
        Bankruptcy</u></font>. Nothing herein shall limit or prejudice the right of Landlord to prove and obtain in a proceeding for bankruptcy, insolvency, arrangement or reorganization, by reason of the termination, an amount equal to the maximum allowed
    by a statute or Applicable Law in effect at the time when, and governing the proceedings in which, the damages are to be proved, whether or not the amount is greater to, equal to, or less than the amount of the loss or damage that Landlord has
    suffered.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">40</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Landlord Default</u></font>. If
    Landlord shall fail to perform any material obligation under this Lease required to be performed by Landlord, Landlord shall not be deemed to be in default hereunder nor subject to claims for damages of any kind, unless such failure shall have
    continued for a period of thirty (30) days after written notice thereof by Tenant or, if such failure is curable but cannot reasonably be cured during such 30-day period, such additional time as it would reasonably take to cure. If Landlord shall fail
    to cure within the time permitted for cure herein, Landlord shall be liable to Tenant for those actual damages sustained by Tenant as a result of Landlord&#8217;s default and Tenant shall also have the right to pursue injunctive relief against Landlord, to
    the extent available under Applicable Laws. Except as may be expressly provided in this Lease, in no event shall Tenant have the right to terminate the Lease nor shall Tenant&#8217;s obligation to pay Base Rent or other charges under this Lease abate based
    upon any default by Landlord of its obligations under the Lease. In no event shall Landlord or any Landlord Related Party ever be liable to Tenant for loss of profits, loss of business, or indirect or consequential damages suffered by Tenant from
    whatever cause.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">8.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Waiver</u></font>. The failure of
    Landlord to insist upon strict performance of any of the terms, covenants, conditions or agreements contained herein shall not be deemed a waiver of any rights or remedies that Landlord may have, and shall not be deemed a waiver of any subsequent
    breach or default in the performance of any of the terms, covenants, conditions or agreements contained herein. The performance of each and every term, covenant, condition and agreement to be performed by Landlord pursuant to this Lease shall not be a
    condition precedent to Landlord&#8217;s right to collect Rent or to enforce this Lease. Further, pursuant to the requirements of California Code of Civil Procedure Section 1161.1(c), Tenant is hereby placed on actual notice that Landlord&#8217;s acceptance of Rent
    shall not constitute a waiver by Landlord of (a) any preceding breach by Tenant of any provision of this Lease, other than the failure of Tenant to pay the particular Rent so accepted; or (b) any of Landlord&#8217;s rights, including, without limitation, any
    rights Landlord may have to recover possession of the Premises or to sue for any remaining Rent owed by Tenant.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article 9<br>
      CASUALTY &amp; CONDEMNATION</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Casualty</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Generally</u></font>. Subject to <u>Section


      9.1.2</u> below, if the Premises are damaged by fire, the elements or other casualty (collectively a &#8220;<b>Casualty</b>&#8221;), Tenant shall promptly notify Landlord of the same. Except as expressly set forth below, this Lease shall not terminate in the
    event of damage to the Premises by other casualty, nor any other obligation of Tenant hereunder be abated or affected in any way. If all or any portion of the Premises becomes untenantable or inaccessible by a Casualty, Landlord shall cause a general
    contractor selected by Landlord to provide Landlord and Tenant with a written estimate of the amount of time required, using standard working methods, to substantially complete the repair and restoration of the affected portion of the Premises (&#8220;<b>Completion


      Estimate</b>&#8221;). Landlord shall promptly forward a copy of the Completion Estimate to Tenant. Notwithstanding anything to the contrary contained in this Lease, Landlord and Tenant hereby waive the provisions of any Law relating to the matters
    addressed in this Section, and agree that their respective rights for damage to or destruction of the Premises shall be those specifically provided in this Lease, which shall constitute an express agreement between the parties with respect thereto, and
    Landlord and Tenant hereby agree that any Applicable Law, including Sections 1932(2) and 1933(4) of the California Civil Code, with respect to any rights or obligations concerning damage or destruction of leased or hired property, shall have no
    application to this Lease or to any damage or destruction to all or any part of the Premises.<font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Termination</u>. </font>Notwithstanding


    <u>Section 9.1.1</u>, if the Completion Estimate indicates that the Premises cannot be made tenantable within twenty-four (24) months from the date the repair is started, then either party shall have the right to terminate this Lease upon written
    notice to the other within ten (10) days after Tenant&#8217;s receipt of the Completion Estimate, which notice, if sent by Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. Tenant, however, shall
    not have the right to terminate this Lease if the Casualty was caused by the negligence or intentional misconduct of Tenant or any Tenant Parties. If (i) the Completion Estimate indicates that the Premises can be made tenantable within thirty-six (36)
    months from the date the repair is started, and (ii) Tenant terminates this Lease pursuant to the first sentence of this <u>Section 9.1.2</u>., then, within thirty (30) days after receipt of Tenant&#8217;s termination notice, Landlord may, in its sole and
    absolute discretion, negate Tenant&#8217;s termination by providing notice to Tenant that Landlord agrees to an abatement of Base Rent beginning immediately following the twenty-fourth (24<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>) month after the date the repair is started and ending on the date when Landlord has substantially completed the repair and restoration of the affected portion of the Premises. In addition, if the Premises are damaged by fire, the
    elements or other casualty during the last twelve (12) months of the Term, and the Completion Estimate shows that the restoration cannot be completed within one hundred twenty (120) days after the Casualty, then either party shall have the right, in
    lieu of Tenant fulfilling its obligations under <u>Section 9.1.1</u> above, to terminate this Lease as of the date of the Casualty by notice to the other party within ten (10) business days after the delivery of the Completion Estimate, which notice,
    if sent by Tenant, shall be accompanied by a sum equal to all Rent due from Tenant to Landlord to the date of termination. If Tenant elects to terminate the Lease pursuant to this <u>Section 9.1.2</u>, Tenant shall (1) assign to Landlord all of
    Tenant&#8217;s right, title and interest in and to any property insurance proceeds received in connection with such casualty for the Tenant Improvements (defined below) and (2) pay to Landlord an amount equal to Tenant&#8217;s deductible under any insurance and/or
    any applicable self-insured retention amount covering the Tenant Improvements. In addition, Landlord, by notice to Tenant within ninety (90) days after the date of the Casualty, shall have the right to terminate this Lease if (1) any Mortgagee requires
    that the insurance proceeds be applied to the payment of the mortgage debt; or (2) a material uninsured loss to the Buildings or Premises occurs, and, in either case, Tenant does not provide Landlord with sufficient funds (or evidence of the same
    satisfactory to Landlord) to complete such restoration within thirty (30) days after Landlord&#8217;s termination notice.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Restoration</u></font>. If this
    Lease is not terminated, Landlord shall promptly and diligently, subject to reasonable delays for insurance adjustment or other matters beyond Landlord&#8217;s reasonable control, restore the core and shell of the Buildings and structural elements of other
    improvements situated upon the Premises, subject to the following provisions. Such restoration shall be to substantially the same condition that existed prior to the Casualty, except for modifications required by Applicable Law or any other
    modifications deemed desirable by Landlord (&#8220;<b>Landlord&#8217;s Restoration</b>&#8221;). Landlord shall be paid a construction management fee equal to three percent (3%) of the hard and soft costs of construction in connection with Landlord&#8217;s Restoration. In no
    event shall Landlord be required to spend more for the Landlord&#8217;s Restoration than the proceeds received by Landlord, whether from Landlord&#8217;s insurance proceeds or proceeds from Tenant. Landlord shall not be liable for any inconvenience to Tenant, or
    injury to Tenant&#8217;s business resulting in any way from the Casualty or the repair thereof. Landlord shall not be responsible for restoration of any portion of the non-structural tenant improvements, any improvements or fixtures installed for Tenant&#8217;s
    specific business operations, or any Alterations, including, without limitation, the Conference Center Alterations (collectively, the &#8220;<b>Tenant Improvements</b>&#8221;). If this Lease is not terminated, upon the substantial completion of Landlord&#8217;s
    Restoration, Tenant shall diligently and promptly repair all such damage and restore the Tenant&#8217;s Improvements (the &#8220;<b>Tenant&#8217;s Restoration</b>&#8221;) to substantially the same quality, use and usability to the Buildings and related improvements that
    existed immediately prior to the Casualty.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No abatement of Rent</u></font>. If
    the Premises are damaged or destroyed by casualty, then the Rent shall not be abated and Tenant shall not be entitled to any compensation or damages from Landlord for loss of the use of the Premises, damage to Tenant&#8217;s Personalty or to any Alterations,
    or any inconvenience occasioned by any damage, repair, or restoration.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.1.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Insurance Proceeds</u>.</font>
    Tenant shall be entitled to any and all of the insurance proceeds payable for the damage to the Tenant Improvements, <u>provided</u>, <u>however</u>, that if Tenant elects to terminate this Lease pursuant to <u>Section 9.1.2</u>, then Tenant shall
    assign and pay over to Landlord all insurance proceeds received by or payable to Tenant with respect to damage to the core and shell of the Buildings and structural elements of other improvements situated upon the Premises (but not Tenant Improvements
    and Tenant&#8217;s Personalty). Whether or not Tenant so elects to terminate this Lease, Tenant shall be entitled to any and all of the insurance proceeds payable for the damage to Tenant&#8217;s Personalty.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Waiver</u></font>. Tenant (for itself
    and all others claiming through Tenant) irrevocably waives and releases its rights to make repairs at Landlord&#8217;s expense. The provisions of this Lease, including this <u>Section 9.2</u>, constitute an express agreement between Landlord and Tenant with
    respect to any damage to, or destruction of, any portion of the Premises. Any law in respect of any rights or obligations concerning any such damage or destruction in the absence of an express agreement between the parties, and any other law relating
    to damage or destruction of leased premises, whether in effect on the date of this Lease or thereafter, shall have no application to this Lease or any damage or destruction of any part of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Total Condemnation</u></font>. If
    after the execution of this Lease and prior to the expiration of the Term, all or a significant portion of the Premises shall be permanently taken under power of eminent domain by any public or private authority, or conveyed by Landlord to said
    authority in lieu of such taking (collectively, a &#8220;<b>Taking</b>&#8221;), and if as a result of such Taking: (a) access to the Premises to and from the publicly dedicated roads adjacent to the Premises as of the Effective Date is permanently and materially
    impaired such that Tenant no longer has access to such dedicated road; (b) there is insufficient parking to operate the Premises under Applicable Laws and replacement parking cannot be constructed or provided elsewhere on the Premises; or (c) the
    taking includes a portion of the Buildings such that the remaining portions are unsuitable for the Permitted Use and the remaining portions of the Premises cannot, in the reasonable opinion of a contractor mutually agreed upon by Landlord and Tenant,
    be restored to useful condition within eighteen (18) months after the Taking (such event, a &#8220;<b>Total Condemnation</b>&#8221;), then, in such event:</p>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Termination</u></font>. On the date
    of the Total Condemnation, this Lease shall automatically terminate; <u>provided</u>, <u>however</u>, that Tenant&#8217;s obligations under any indemnification provisions of this Lease and Tenant&#8217;s obligation to pay Rent and all other monetary obligations
    (whether payable to Landlord or a third party) accruing under this Lease prior to the date of termination shall survive such termination. If the date of such Total Condemnation is other than the first day of a month, the Base Rent for the month in
    which such Total Condemnation occurs shall be apportioned based on the date of the Total Condemnation</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Award</u>. Landlord shall be
      entitled to receive the entire award payable in connection with a Total Condemnation without deduction for any estate vested in Tenant by this Lease, and Tenant hereby expressly assigns to Landlord all of its right, title and interest in and to every
      such award and agrees that Tenant shall not be entitled to any such award or other payment for the value of Tenant&#8217;s leasehold interest in this Lease; <u>provided</u>, <u>however</u>, that Tenant shall have the right to file any separate claim
      available to Tenant for any taking of Tenant&#8217;s Personalty, loss of goodwill, and for moving and relocation expenses (but only if such payment to Tenant does not reduce any award available to Landlord). </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">9.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Partial Condemnation</u></font>. In
    the event of a Taking which is not a Total Condemnation, neither party shall have the right to terminate this Lease and Landlord shall, using proceeds therefor from the condemning authority, restore the core and shell of the Buildings and structural
    elements of other improvements situated upon the Premises reasonably sufficient to make a functional unit of the remaining portion of the Premises, and Tenant shall proceed with restoration of the Tenant Improvements to the extent possible to make a
    functional unit of the remaining portion of the Premises. In the event any partial taking materially affects Tenant&#8217;s operations in the Buildings for the Permitted Use, such that the Premises no longer provides sufficient space for Tenant to carry out
    its business without material interference with the Permitted Use, then, commencing on the date on which Tenant&#8217;s operations are materially affected, the Base Rent shall be abated in proportion to the square footage of the portion of the Buildings
    taken.&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article 10<br>
    </font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>MISCELLANEOUS</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">10.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Notices</u></font>. Any notice, consent, demand, or
    other communication or document required or permitted to be given under this Lease or pursuant to any law (&#8220;<b>Notice(s)</b>&#8221;), shall be (a) in writing (except as otherwise provided in this Lease), (b) addressed to the intended recipient at its address
    set forth in the Basic Lease Information (provided that each of Landlord and Tenant may change its addresses for the giving of notices by giving written notice thereof to the other party), (c) sent by fully prepaid registered or certified United States
    Mail return receipt requested, or by any nationally recognized overnight courier service furnishing a written record of attempted or actual delivery, and (d) deemed to have been delivered upon actually delivery or rejection of delivery. Any Notice may
    be given by an attorney on behalf of Landlord or Tenant.</p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Certain Representations</u></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.2.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;Neither of Tenant nor any
      wholly-owned subsidiary of Tenant is (i) in violation of any OFAC Law or Regulation, the U.S. Patriot Act or Anti-Corruption Legislation, (ii) is named by any Executive Order (including the September 23, 2001, Executive Order Blocking Property and
      Prohibiting Transactions With Persons Who Commit, Threaten to Commit, or Support Terrorism) or the United States Treasury Department as a terrorist, &#8220;Specially Designated National and Blocked Person,&#8221; or (iii) (to the Tenant&#8217;s knowledge) acting,
      directly or indirectly, on behalf of any such person. To Tenant&#8217;s actual knowledge, no such person, group, entity or nation owns 20% or more Tenant&#8217;s voting securities. To the Tenant&#8217;s knowledge, the monies used in connection with this Agreement and
      amounts committed with respect thereto, were not and are not derived from any activities that contravene any applicable OFAC Laws and Regulations, the U.S. Patriot Act, AML Legislation or Anti-Corruption Legislation, each as defined below.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.2.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;As used herein, the term &#8220;<b>AML
        Legislation</b>&#8221; means United States anti-money laundering-related and anti-terrorism financing laws, regulations, and codes of practice applicable to the Tenant, its affiliates, and their operations from time to time, including, any regulations,
      guidelines or orders thereunder. As used herein, the term &#8220;<b>Anti-Corruption Legislation</b>&#8221; means U.S. Foreign Corrupt Practices Act and similar anticorruption and anti-bribery laws of the United States. As used herein, the term &#8220;<b>OFAC Laws and
        Regulations</b>&#8221; means (i) any lists, laws, rules, sanctions and regulations maintained by OFAC pursuant to any authorizing statute, Executive Order or regulation, including the Trading with the Enemy Act, 50 U.S.C. App. &#167; 1 et seq., the
      International Emergency Economic Powers Act, 50 U.S.C. &#167; 1701 et seq., the Iraq Sanctions Act, Pub. L. 101-513, Title V, &#167;&#167; 586 to 586J, 104 Stat. 2047, the National Emergencies Act, 50 U.S.C. &#167;&#167; 1601 et seq., the Antiterrorism and Effective Death
      Penalty Act of 1996, Pub. L. 104- 132, 110 Stat. 1214-1319, the United Nations Participation Act, 22 U.S.C. &#167; 287c, the International Security and Development Cooperation Act, 22 U.S.C. &#167; 2349aa-9, the Nuclear Proliferation Prevention Act of 1994,
      Pub. L. 103-236, 108 Stat. 507, the Foreign Narcotics Kingpin Designation Act, 21 U.S.C. &#167;&#167; 1901 et seq., the Iran and Libya Sanctions Act of 1996, Pub. L. 104-172, 110 Stat. 1541, the Cuban Democracy Act, 22 U.S.C. &#167;&#167; 6001 et seq., the Cuban Liberty
      and Democratic Solidarity Act, 22 U.S.C. &#167;&#167; 6021-91, and the Foreign Operations, Export Financing and Related Programs Appropriations Act, 1997, Pub. L. 104-208, 110 Stat. 3009-172; (ii) all regulations, executive orders, or administrative orders of
      any kind issued under these statutes, including 31 C.F.R., Subtitle B, Chapter V; and (iii) any other applicable United States civil or criminal federal or state laws, regulations, or orders that (1) limit the use of and/or seek the forfeiture of
      proceeds from illegal transactions; (2) limit commercial transactions with designated countries or individuals believed to be terrorists, narcotics dealers or otherwise engaged in activities contrary to the interests of the United States; or (3) are
      designed to disrupt the flow of funds to terrorist organizations, as all of the foregoing laws may be amended from time to time.</font></p>
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    and Tenant represents and warrants to the other that such party has not dealt with any broker or finder in connection with this Lease. Each party shall indemnify the other and hold it harmless from any cost, expense, or liability (including costs of
    suit and reasonable attorneys&#8217; fees) for any compensation, commission or fees claimed by any other real estate broker or agent in connection with this Lease or its negotiation by reason of any act or statement of the indemnifying party.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Waivers</u></font>. No provision
    of this Lease shall be deemed waived by either party unless expressly waived in a writing signed by the waiving party (and then only to the extent so expressly waived). No waiver shall be implied by delay or any other act or omission of either party.
    No waiver by either party of any provision of this Lease shall be deemed a waiver of such provision with respect to any subsequent matter relating to such provision, and Landlord&#8217;s consent or approval respecting any action by Tenant shall not
    constitute a waiver of the requirement for obtaining Landlord&#8217;s consent or approval respecting any subsequent action. No act or thing done by Landlord or its agents during the Term shall be deemed a termination of this Lease, an acceleration of the
    Termination Date, or an acceptance of the surrender of the Premises, and no agreement to terminate this Lease, accelerate the Termination Date, or accept a surrender of the Premises shall be valid, unless expressly provided in a writing signed by
    Landlord. Acceptance of the full or any partial payment of Rent shall not be deemed Landlord&#8217;s waiver of any breach by Tenant of any provision of this Lease and Landlord&#8217;s acceptance of a lesser amount than the Rent due under this Lease shall not be
    deemed Landlord&#8217;s waiver of Landlord&#8217;s right to receive the full amount of Rent due, nor shall any endorsement or statement on any check or payment or any letter accompanying such check or payment be deemed an accord and satisfaction, and Landlord may
    accept such partial payment without prejudice to Landlord&#8217;s right to recover the full amount of Rent due. Tenant acknowledges that this <u>Section 10.4</u> imparts actual notice to Tenant that Landlord&#8217;s acceptance of partial payment of Rent does not
    constitute a waiver of any of Landlord&#8217;s rights, including any right Landlord may have to recover possession of the Premises. Forbearance by Landlord in enforcing one or more of the remedies provided in this Lease upon an Event of Default shall not be
    deemed a waiver of such Event of Default or of Landlord&#8217;s right to enforce any such remedies with respect to such Event of Default or any subsequent Event of Default. Landlord&#8217;s acceptance of any Rent or of the performance of any other provision of
    this Lease from any person other than Tenant, including any Transferee, shall not be deemed a waiver of Landlord&#8217;s right to approve any Transfer in accordance with <u>Article 5</u>.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Future Development</u>. Provided the
      Tenant is Ionis Pharmaceuticals, Inc., or an affiliate, and Tenant is operating for the Permitted Use, in no event shall Landlord take any action or permit any actions to be taken that may or will increase or decrease, modify, change or alter the
      zoning or entitlements of the Premises, alter the Buildings, change the site amenities, or add additional improvements without the express written consent of Tenant. Notwithstanding the foregoing, subject to the terms of this Section 10.5, Landlord
      reserves all rights as may be necessary or desirable to construct additional improvements serving the Premises, the Companion Premises, or both, in connection with the construction of the improvements under the Companion Lease, including, without
      limitation, pedestrian walkways, installation of utilities and utility connections, structured parking, a pedestrian bridge, and site improvements at the Premises, and to modify the Buildings in connection with any such additional development, all as
      required by the Companion Lease and consistent with the plans and specifications for the construction of the Companion Premises (&#8220;<b>Future Development</b>&#8221;). In connection with any such Future Development, facilities at the Premises may be
      eliminated, altered, or relocated and may also be utilized to serve the Companion Premises. The rights set forth above shall include rights to use portions of the Premises for the purpose of temporary construction staging and related activities and
      to implement valet parking for reserved and unreserved parking spaces for the purpose of facilitating construction during such activities.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.5.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;Landlord and its representatives,
      contractors, agents, employees and licensees shall have the right during any construction period to enter the Premises to undertake such work; to shore up the foundations, walls, and other improvements at the Premises; to erect scaffolding and
      protective barricades around the Premises; and to do any other act necessary for the safety of the improvements at the Premises or the expeditious completion of such construction. Landlord shall use reasonable efforts not to interfere with the
      conduct of Tenant&#8217;s business and to minimize the extent and duration of any inconvenience, annoyance or disturbance to Tenant resulting from any work pursuant to this Section in or about the Premises, consistent with accepted construction practice,
      and so long as Landlord uses such reasonable efforts Landlord shall not be liable to Tenant for any compensation or reduction of Rent by reason of inconvenience or annoyance or for loss of business resulting from any act by Landlord pursuant to this
      Section.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.5.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant agrees to enter into any
      instruments reasonably requested by Landlord in connection with the Future Improvements, and for the continued maintenance of such Future Improvements, so long as the same do not materially decrease the rights or materially and adversely increase the
      obligations of Tenant under this Lease, including reciprocal easement agreements, declarations of covenants, and other agreements to facilitate use of the improvements between the Premises and Companion Premises. Tenant agrees not to take any action
      to oppose any application by Landlord for any permits, consents or approvals from any governmental authorities for any redevelopment or additional development of all or any part of the Companion Premises, and will use all commercially reasonable
      efforts to prevent any of Tenant&#8217;s subtenants or assigns, and Tenant&#8217;s and their respective officers, directors, employees, agents, contractors and consultants from doing so. For purposes hereof, action to oppose any such application shall include,
      without limitation, communications with any governmental authorities requesting that any such application be limited or altered. Also for purposes hereof, commercially reasonable efforts shall include, without limitation, commercially reasonable
      efforts, upon receiving notice of any such action to oppose any application on the part of any Tenant Parties, to obtain injunctive relief, and, in the case of a subtenant, exercising remedies against the subtenant under its sublease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Other Provisions</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Covenant of Quiet Enjoyment</u></font>.
    Landlord covenants that Tenant, while no Event of Default has occurred and be continuing, shall peaceably and quietly have, hold, and enjoy the Premises for the Term without hindrance from Landlord, but not otherwise, subject to all matters of record
    and to the terms and provisions of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Survival</u></font>. All
    obligations of Tenant under this Lease not fully performed as of the Termination Date shall survive the Termination Date.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Entire Agreement</u></font>. This
    Lease, together with the Exhibits, contains all of the agreements of Landlord and Tenant in respect of this Lease and supersedes any previous negotiations. There have been no representations made by Landlord or any of Landlord&#8217;s representatives, or
    understandings made between Landlord and Tenant, other than those set forth in this Lease and the Exhibits. This Lease may not be modified except by a written instrument duly executed by the party to be bound. Landlord and Tenant each represent to the
    other, that is has the individuals executing this Lease have been properly authorized by proper action of the Landlord and Tenant, as the case may be.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Execution in Counterparts</u></font>.
    This Lease may be executed in counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same instrument.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Recording</u>. Tenant shall not
      record this Lease, but may record a short form memorandum of this Lease in the form attached hereto as <u>Exhibit D</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Discrimination</u></font>.
    Tenant shall not (and Tenant shall not permit any person claiming through or under Tenant to) discriminate against or segregate any person or group of persons on account of race, color, creed, sex, religion, marital status, ancestry, or national
    origin, whether in the use, occupancy, subleasing, transferring, or enjoyment of the Premises, or otherwise.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.7&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Attorneys&#8217; Fees</u></font>. In any
    action or proceeding that Landlord or Tenant initiates against the other party declaratory or otherwise, arising out of this Lease, the unsuccessful party in such action or proceeding shall reimburse the prevailing party for its costs, including
    reasonable attorneys&#8217; fees (at trial and appellate levels).</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.8&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Waiver of Consequential Damages</u></font>.
    Except as set forth in <u>Section 1.3</u> and <u>Section 3.3</u>, neither Landlord nor Tenant shall be liable to the other for any form of special, indirect, consequential, or punitive damages.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.9&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tenant Information</u></font>.
    Upon Landlord&#8217;s request from time to time, Tenant shall provide to Landlord the financial statements for Tenant for its most recent fiscal year and fiscal quarter. Financial statements for each fiscal year shall be prepared and certified by a certified
    public accountant; financial statements for each quarter shall be prepared and certified by Tenant&#8217;s chief financial officer. In addition, if so requested, and provided that Landlord may not require such information more than once in any calendar year
    except where Landlord has reasonable grounds for concern, details of the financial and credit standing and details of the corporate organization of Tenant and any Indemnitor, including copies of financial statements for the last three (3) fiscal years
    of Tenant. If requested by Tenant, such financial statements shall be furnished pursuant to a confidentiality agreement in a form reasonably provided by Landlord for such purpose. The provisions of this Section 10.6.9 shall not apply to Tenant if it is
    a Public Company and its financial statements are publicly available.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.6.10&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>REIT Provisions</u></font>.
    Tenant and Landlord intend that all amounts payable by Tenant to Landlord shall qualify as &#8220;rents from real property,&#8221; and will otherwise not constitute &#8220;unrelated business taxable income&#8221; or &#8220;impermissible tenant services income,&#8221; all within the
    meaning of Section 856(d) of the Internal Revenue Code of 1986, as amended (the &#8220;<b>Code</b>&#8221;) and the U.S. Department of Treasury Regulations promulgated thereunder (the &#8220;<b>Regulations</b>&#8221;). In the event that Landlord determines that there is any
    risk that any amount payable under this Lease may not qualify as &#8220;rents from real property&#8221; or will otherwise constitute impermissible tenant services income within the meaning of Section 856(d) of the Code and the Regulations, Tenant agrees to (a)
    cooperate with Landlord by entering into such amendment or amendments as Landlord deems necessary to qualify all amounts payable under this Lease as &#8220;rents from real property&#8221; and (b) permit (and, upon request, to acknowledge in writing) an assignment
    of the obligation to provide certain services under the Lease, and, upon request, to enter into direct agreements with the parties furnishing such services (which shall include but not be limited to a taxable REIT subsidiary of Landlord).
    Notwithstanding the foregoing, Tenant shall not be required to take any action pursuant to the preceding sentence (including acknowledging in writing an assignment of services pursuant thereto) if such action would result in (A) Tenant&#8217;s incurring more
    than de minimis additional liability under this Lease or (B) more than a de minimis negative change in the quality or level of Buildings operations or services rendered to Tenant under this Lease. For the avoidance of doubt, (i) if Tenant does not
    acknowledge in writing an assignment as described in clause (b) above (it being agreed that Tenant shall not unreasonably withhold, condition or delay such acknowledgment so long as the criteria in clauses (A) and (B), above, are satisfied), then
    Landlord shall not be released from liability under this Lease with respect to the services so assigned; and (ii) nothing in this Section 10.6.10 shall limit or otherwise affect Landlord&#8217;s ability to assign its entire interest in this Lease to any
    party as part of a conveyance of Landlord&#8217;s ownership interest in the Buildings.</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Interpretation</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Captions</u></font>. The captions
    in this Lease are for convenience of reference and shall not define, increase, limit, or describe the scope or intent of any provision of this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Landlord and Tenant</u></font>.
    The terms &#8220;Tenant&#8221; and &#8220;Landlord&#8221;, and any pronoun used in place thereof, shall indicate and include each of the parties&#8217; and respective successors, executors, administrators, and permitted assigns, according to the context, provided that, for the
    purposes of any provisions indemnifying or waiving claims against, Landlord, the term &#8220;Landlord&#8221; shall also include Landlord&#8217;s present and future investment manager, and property management company, and all of their trustees, directors, officers,
    partners, beneficiaries, principals, members, managers, investors, stockholders, employees, Affiliates, agents, representatives, contractors (and subcontractors of any tier), successors and assigns.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Non-Exclusivity</u></font>.
    Whenever the words &#8220;including&#8221;, &#8220;include&#8221;, or &#8220;includes&#8221; are used in this Lease, they shall be interpreted in a non-exclusive manner as though the words &#8220;without limitation&#8221; immediately followed the same. Any reference to &#8220;any part&#8221; or &#8220;any portion of&#8221;
    the Premises or any other property shall be construed to refer to all or any part of the same.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.4&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Covenants Independent</u></font>.
    This Lease shall be construed as though the covenants herein between Landlord and Tenant are independent.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">49</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.5&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Joint and Several Liability</u></font>.
    In any case where either Landlord or Tenant consists of more than one person, the obligations of such party under this Lease shall be joint and several.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.6&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Time of the Essence</u></font>.
    Time is of the essence of this Lease and all of its provisions.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.7&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Governing Law</u></font>. This
    Lease shall in all respects be governed by the laws of the State of California without giving effect to the principles of conflicts of law thereof or of any other jurisdiction that would result in the application of the Applicable Laws of any other
    jurisdiction. Tenant&#8217;s obligation to pay Rent shall not be discharged or otherwise affected by any Applicable Law or regulation now or hereafter applicable to the Premises, or any other restriction on Tenant&#8217;s use, or (except as expressly provided in
    this Lease) any Casualty or Taking, or any failure by Landlord to perform any covenant contained herein, or any other occurrence; and no termination or abatement remedy that is not expressly provided for in this Lease for any breach or failure by
    Landlord to perform any obligation under this Lease shall be implied or applicable as a matter of Applicable Law.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.8&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Successors and Assigns</u></font>.
    Subject to the provisions of <u>Article 5</u>, the provisions of this Lease shall be binding upon and inure to the benefit of the heirs, successors, executors, administrators, and assigns of Landlord and Tenant.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.7.9&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Submission</u></font>. The
    submission of this Lease to Tenant or a summary of some or all of its provisions for examination does not constitute a reservation of or option for the Premises or an offer to lease, and no legal obligations shall arise with respect to the Premises or
    other matters herein unless and until such time as this Lease is executed and delivered by Landlord and Tenant and approved by the holder of any mortgage on the Buildings having the right to approve this Lease.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.8&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tenant&#8217;s Signage</u></font>. Tenant
    shall have the right to install such signage at or upon the Premises as permitted by Applicable Laws. Tenant, at its sole expense, shall maintain Tenant&#8217;s Signage in good condition and repair during the Term. Should Tenant&#8217;s Signage require maintenance
    or repairs as determined in Landlord&#8217;s reasonable judgment, Landlord shall have the right to provide notice thereof to Tenant and Tenant shall cause such repairs and/or maintenance to be performed within thirty (30) days after receipt of such notice
    from Landlord at Tenant&#8217;s sole cost and expense. Should Tenant fail to perform such maintenance and repairs within the period described in the immediately preceding sentence, then, in addition to all of Landlord&#8217;s other rights and remedies, Landlord
    may, but need not, perform the required maintenance and repairs, and Tenant shall pay Landlord the cost thereof, plus a fee for Landlord&#8217;s oversight and coordination of such work equal to five percent (5%) of its cost, within thirty (30) days after
    receipt of Landlord&#8217;s request for payment, together with reasonable, supporting backup documentation. Landlord shall have the right to maintain one or more signs at the Premises in a prominent location near the entrance to the Building identifying the
    property manager and the identity of Landlord or its direct or indirect ownership group in a manner similar to that shown on <u>Exhibit G</u> attached, subject to Tenant&#8217;s approval of the size and location of such signage, such approval not to be
    unreasonably withheld, conditioned or delayed.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.9&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Choice of Law</u>.</font> This Lease
    shall be governed by the Applicable Laws of the State of California.</p>
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    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">50</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.10&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>CASp Inspection</u></font>. For
    purposes of Section 1938(a) of the California Civil Code, Landlord hereby discloses to Tenant, and Tenant hereby acknowledges, that neither the Buildings nor any portion of the Premises has undergone inspection by a Certified Access Specialist (CASp)
    (defined by California Civil Code Section 55.52). Pursuant to California Civil Code Section 1938, Tenant is hereby notified as follows: &#8220;A Certified Access Specialist (CASp) can inspect the subject premises and determine whether the subject premises
    comply with all of the applicable construction-related accessibility standards under state law. Although state law does not require a CASp inspection of the subject premises, the commercial property owner or lessor may not prohibit the lessee or tenant
    from obtaining a CASp inspection of the subject premises for the occupancy of the lessee or tenant, if requested by lessee or tenant. The parties shall mutually agree on the arrangements for the time and manner of any CASp inspection, the payment of
    the fee for the CASp inspection and the cost of making any repairs necessary to correct violations of construction-related accessibility standards within the premises.&#8221; If Tenant requests to perform a CASp inspection of the Premises, Tenant shall, at
    its cost, retain a CASp approved by Landlord to perform the inspection of the Premises at a time agreed upon by the parties. Tenant shall provide Landlord with a copy of any report or certificate issued by the CASp (the &#8220;<b>CASp Report</b>&#8221;). Landlord
    and Tenant agree that any modifications necessary to correct violations of construction related accessibility standards identified in the CASp Report shall be the responsibility of Tenant. Tenant agrees to keep the information in the CASp Report
    confidential except as necessary for the Tenant to complete such modifications.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10.11&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Landlord Access</u></font>.
    Landlord, its affiliates, and their respective contractors and agents, subject to the terms of this Section 10.11, may, (a) at any and all reasonable times during normal business hours (or during non-business hours, if Landlord so requests and Tenant
    consents), and upon at least two (2) business days&#8217; prior notice (which may be oral or by email to the office manager or other Tenant-designated individual at the Premises; but provided that no time restrictions shall apply or advance notice be
    required if a bona fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry and any oral notice will be followed immediately by email notice as provided above prior to entry), enter the Premises to (i)
    inspect the same and to determine whether Tenant is in compliance with its obligations hereunder, (ii) supply any service Landlord is required to provide hereunder, (iii) alter, improve or repair any portion of the premises under the Companion Lease
    for which access to or through the Premises is reasonably necessary, (iv) post notices of non-responsibility, (v) show the Premises to current and prospective investors, lenders and purchasers, and (vii) show the Premises, other than the Secure Access
    Areas, during the final eighteen (18) months of the Term (provided that Tenant has not timely exercised an Extension Option to extend the Term pursuant to Section 1.4) to prospective tenants, and (b) notwithstanding the foregoing, at any and all
    reasonable times during business and non-business hours and upon at least two (2) business days&#8217; prior notice enter the Premises for the purposes of performing any repairs or maintenance that Landlord is obligated or entitled to perform pursuant to
    this Lease (provided that no time restrictions shall apply if a bona fide emergency with an immediate threat to property damage or personal injury necessitates immediate entry); provided, however, that Landlord shall comply with Tenant&#8217;s reasonable
    safety procedures and protocols with respect to the Premises, and with respect to portions of the Premises (if any) that are reasonably designated in writing by Tenant to Landlord as controlled or having restricted access (the &#8220;<b>Secure Access Areas</b>&#8221;),


    shall comply with Tenant&#8217;s reasonable additional security and safety procedures and protocols related to such portions of the Premises including only entering such designated Secure Access Areas when accompanied by a Tenant representative (provided
    further, that Tenant shall provide a Tenant representative to accompany Landlord upon written request from Landlord at least two (2) business days&#8217; in advance). In no event shall Tenant&#8217;s Base Rent abate as a result of Landlord&#8217;s activities pursuant to
    this Section; provided, however, that all such activities shall be conducted in such a manner so as to cause as little interference to Tenant as is reasonably possible. Landlord shall at all times retain keys, key cards and access codes with which to
    unlock all of the doors in the Premises. Landlord acknowledges that the standard operating procedures set forth on <u>Exhibit L</u> shall apply to the issuance to Landlord of any key cards, electronic keypad codes, or door keys to any Secure Access
    Areas for any unaccompanied access too the Premises by Landlord, provided, however, that Tenant shall identify a single designee to act as Landlord&#8217;s point of contact to administer the requirements of Tenant&#8217;s standard operating procedures on behalf of
    Landlord and that in no event shall any such requirements prohibit Landlord&#8217;s entry into Secure Access Areas (i) in the event of a bona fide emergency with an immediate threat to property damage or personal injury that necessitates immediate entry or
    (ii) when accompanied by a representative of Tenant. If an emergency necessitates immediate access to the Premises, Landlord may use whatever force is necessary to enter the Premises, and any such entry to the Premises shall not constitute a forcible
    or unlawful entry to the Premises, a detainer of the Premises, an eviction of Tenant from the Premises or any portion thereof, or a violation of the provisions of this Section 10.11. Notwithstanding anything herein to the contrary, in the event Tenant
    notifies Landlord within one (1) business day (which may be oral or by email to the Landlord-designated individual) following Landlord&#8217;s request for access that the proposed day and/or time for entry will cause a disruption to a planned event, meeting
    or other programming for Tenant, Landlord and Tenant shall cooperate with one another to identify a better date and/or time Landlord&#8217;s entry of the Premises.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Article 11<br>
      TENANT&#8217;S RIGHT OF FIRST OFFER</font></p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-transform: uppercase; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Right of First Offer</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.1.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notwithstanding anything contained in this Lease to the
      contrary, provided that (i) no Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or its affiliate, if Landlord intends to offer the Premises (or any portion thereof) for sale to an
      unaffiliated third party, Landlord shall promptly notify Tenant of the same in writing (the &#8220;<b>Offer Notice</b>&#8221;) and indicate the terms and conditions upon which Landlord is willing to accept for the sale of the Premises to a third party. Tenant
      may elect to purchase the Premises (or portion thereof) on the terms and conditions set forth in the Offer Notice by notifying Landlord in writing (the &#8220;<b>Election Notice</b>&#8221;) of its election no later than fifteen (15) days after the Offer Notice,
      which notice shall be accompanied by the Option Deposit (defined herein), and the sale of the Premises shall be consummated pursuant to the terms hereof on a date (the &#8220;<b>Closing Date</b>&#8221;) within sixty (60) days after the Election Notice, such date
      to be mutually agreed upon by Landlord or Tenant. In the event of any of the following: (x) Tenant fails to deliver the Election Notice or the Option Deposit to Landlord on or before the expiration of the 15-day period set forth above, (y) Tenant
      fails to close on its acquisition of the Premises on or before the Closing Date, or (z) Landlord provides an Offer Notice to Tenant and Tenant does not exercise its right to purchase the Premises, then in each case Tenant shall be deemed to have
      waived its right to purchase the Premises and thereafter Tenant&#8217;s rights under this Article 11 shall be null and void and of no further force or effect. The term &#8220;<b>Option Deposit</b>&#8221; shall mean the amount of cash deposit required in the Offer
      Notice or, if no cash deposit is specified in the Offer Notice, a sum equal to five percent (5%) of the purchase price for the Premises set forth in the Offer Notice.</font></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.1.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Premises is not sold to Tenant
      pursuant to Section 11.1.1 above, Landlord shall have the right to direct the marketing of the Premises (including the unilateral right to select any broker to be utilized), and to take all actions in furtherance thereof, including, without
      limitation, the right and authority to execute, such agreements, documents, instruments and applications, including a purchase and sale agreement and a deed, assignment of leases, bills of sale and other conveyance documents conveying the Premises
      (collectively, &#8220;<b>Sale Documents</b>&#8221;) as Landlord, may reasonably deem necessary or desirable in order consummate such sale, and, subject to <u>Section 11.1.1</u> above and <u>Section 11.2</u> below, Landlord shall be authorized to accept an
      offer for the sale of the Premises. If Landlord modifies the terms of its offer such that the purchase price is less than ninety-five percent (95%) of the consideration provided in the Offer Notice, then the proposed transaction shall again be
      subject to Tenant&#8217;s rights under this Article 11, and Landlord shall deliver an amended Offer Notice to Tenant. </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.1.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant shall, at no material
      out-of-pocket cost to Tenant, reasonably cooperate with Landlord&#8217;s efforts to sell the Premises, including by providing information with respect to the Premises, and by allowing and facilitating physical access to the Premises to prospective
      purchasers and their lenders and consultants, but such cooperation and execution by the Tenant shall not be a condition to the effectiveness of any actions taken by Landlord with respect to such sale or to the effectiveness of Sale Documents. </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tenant&#8217;s Competitors</u>. Provided
      that (i) no Event of Default by Tenant has occurred under this Lease, and (ii) the Tenant is Ionis Pharmaceuticals, Inc., or an affiliate, and such Tenant remains in possession of the Premises and operating for the Permitted Use, Landlord shall not
      sell the Premises (or any portion thereof, or all or substantially all of Landlord&#8217;s interest therein) or enter into an agreement to that would transfer Landlord&#8217;s interest in the Premises to a Competitor during the Term; provided, however, this
      Section 11.2 shall not prohibit Landlord from entering into an agreement to sell or transfer the Premises to a Competitor if the effective date of the transfer would occur after the expiration of the Term. As used herein, &#8220;<b>Competitor</b>&#8221; or &#8220;<b>Competitors</b>&#8221;
      means the companies expressly listed as competitors in Tenant&#8217;s most recent publicly filed Annual Report (10-K); provided, however, (1) such companies shall be directly engaged in the development, manufacturing, or commercializing a medicine or other
      life sciences product, and &#8220;Competitor&#8221; shall not mean any affiliates, investors, parents, or other stake-holders of such companies, and (2) there shall not be more than twenty (20) Competitors at any one time. If Tenant&#8217;s most recent publicly filed
      Annual Report (10-K) includes more than twenty (20) companies that would otherwise be deemed Competitors, only those companies that were previously listed in Tenant&#8217;s Annual Report (10-K) shall be deemed a Competitor unless Tenant provides a written
      notice to Landlord specifying which companies listed in Tenant&#8217;s most recent Annual Report (10-K) shall be included in the list of twenty (20) Competitors for the purposes of this Lease.</font></p>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Excluded Transfers</u>.
      Notwithstanding anything to the contrary herein, Tenant&#8217;s rights under this Article 11 shall not apply to any transaction that meets at least one of the following criteria:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.3.1&#160;&#160;&#160;&#160;&#160;&#160;&#160;any sale/leaseback transaction made
      in connection with a bona fide financing, provided that the seller/lessee under any such transaction shall be bound by the provisions of this Article 11 at such time, if any, as such seller/lessee reacquires title to the Premises;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.3.2&#160;&#160;&#160;&#160;&#160;&#160;&#160;any sale or transfer of the Premises
      to a partnership, corporation, limited liability company, trust or other entity that is under control by, common control with, or controls Landlord or any direct or indirect owner of Landlord, but any such transferee shall hold title subject to
      Tenant&#8217;s rights under this Article 11; </font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11.3.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;any transfer in the nature of a
      financing transaction with a financial institution that is made for a bona fide business purpose (i.e., other than in order to allow a transfer of the Premises in avoidance of Tenant&#8217;s rights under this Article 11), including without limitation the
      granting of, foreclosure under, or giving of a deed-in-lieu of foreclosure under, a mortgage or the granting or exercise of any pledge of ownership interests; provided that, following any foreclosure of the Premises, deed in lieu thereof, or similar
      acquisition of title by a mortgagee, lender, or their affiliates, following the first sale of the Premises by such mortgagee, lender or their affiliates, the subsequent Landlord shall be bound by Tenant&#8217;s rights under this Article 11; </font></p>
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      or indirect interest in Landlord that represents a transfer of less than 80% of such interests (so long as such transfer does not also include the ability to control the day-to-day operations of Landlord); provided that any transferee of direct
      interests in Landlord otherwise described in this Section 11.3.4 is not a Competitor; </font></p>
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      or indirect interest in Landlord on a nationally recognized stock exchange; and</font></p>
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      that includes at least two other real estate assets (excluding the Premises and, if the Companion Lease is in effect, the Companion Premises) that in the aggregate have rentable space at least equal to 416,000 square feet.</font></p>
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      of the Premises, (y) any portfolio transaction sale that includes the Premises, or (z) any foreclosure of a Mortgage on the Premises or conveyance by deed-in-lieu of foreclosure, in each case to a third-party person or entity in accordance with the
      terms of this Article 11, Tenant&#8217;s right of first offer to purchase the Premises under this Article 11 shall forever terminate.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">54</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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      Notice and information in connection therewith, and any information regarding a sale of the Premises, provided to Tenant by Landlord pursuant to this Article 11 shall be held confidential by Tenant and not disclosed to any third party except as
      required by law or in connection with any dispute between Landlord and Tenant regarding this Article 11 and for disclosures to Tenant&#8217;s legal advisors and third-party consultants to the extent such legal advisors and consultants are reasonably
      required for Tenant to evaluate such information and, in each case, provided that such legal advisors and consultants are made subject to the provisions of this paragraph or are otherwise bound by provisional obligations of confidentiality. Any such
      information shall be returned by Tenant to Landlord if Tenant&#8217;s rights under this Article 11 terminate in accordance with the terms hereof. Nothing in this Section 11.5 shall prevent Tenant from making disclosures required by applicable public
      company disclosure laws, provided, however, such disclosures shall include no more information than what is minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to reasonably approve any
      disclosure that exceeds what is minimally necessary to satisfy the legal requirement, and provided further that Landlord shall have the right to review any disclosure prior to the filing of the same for purposes of confirming compliance with the
      terms of this sentence, to the extent that such review is permitted pursuant to Applicable Law.</font>&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"></p>
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      LIMITATION OF LIABILITY</font></p>
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      agrees from time to time to look only to Landlord&#8217;s interest in the Premises for satisfaction of any claim against Landlord hereunder or under any other instrument related to the Lease (including any separate agreements among the parties and any
      notices or certificates delivered by Landlord) and not to any other property or assets of Landlord. If Landlord from time to time transfers its interest in the Premises, then from and after each such transfer Tenant shall look solely to the interests
      in the Premises of Landlord&#8217;s transferees for the performance of all of the obligations of Landlord hereunder (or under any related instrument). The obligations of Landlord shall not be binding on any direct or indirect partners (or members,
      trustees, or beneficiaries) of Landlord or of any successor, individually, but only upon Landlord&#8217;s or such successor&#8217;s interest described above. Further, if Landlord is, or one of the parties comprising Landlord is, or the Lease is assigned to, a
      real estate investment trust (&#8220;<b>REIT</b>&#8221;), the parties acknowledge and agree that the obligations of the REIT hereunder and under all documents delivered pursuant hereto (and all documents to which the Lease may be pursuant) or which give effect
      to, or amend or supplement, the terms of the Lease are not personally binding upon any trustee thereof, any registered or beneficial holder of units (a &#8220;<b>Unitholder</b>&#8221;) or any annuitant under a plan of which a Unitholder acts as a trustee or
      carrier, or any officers, employees or agents of the REIT and resort shall not be had to, nor shall recourse or satisfaction be sought from, any of the foregoing or the private property of any of the foregoing.</font></p>
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      Landlord of Landlord&#8217;s interest in this Lease, or the rents payable hereunder, conditional in nature or otherwise, which assignment is made to the holder of a mortgage on property that includes the Premises, Tenant agrees that the execution thereof
      by Landlord, and the acceptance thereof by the holder of such mortgage shall never be treated as an assumption by such holder of any of the obligations of Landlord hereunder unless such holder shall, by notice sent to Tenant, specifically otherwise
      elect and, except as aforesaid, such holder shall be treated as having assumed Landlord&#8217;s obligations hereunder only upon foreclosure of such holder&#8217;s mortgage and the taking of possession of the Premises.</font></p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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      Landlord&#8217;s interest in the Premises by a purchaser that, simultaneously therewith, leases Landlord&#8217;s entire interest in the Premises back to the seller thereof be treated as an assumption by operation of Law or otherwise, of Landlord&#8217;s obligations
      hereunder, but Tenant shall look solely to such seller-lessee, and its successors from time to time in title, for performance of Landlord&#8217;s obligations hereunder. In any such event, this Lease shall be subject and subordinate to the lease to such
      purchaser. For all purposes, such seller-lessee, and its successors in title, shall be the Landlord hereunder unless and until Landlord&#8217;s position shall have been assumed by such purchaser-lessor.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: justify; text-indent: 0.9in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">12.2.3&#160;&#160;&#160;&#160;&#160;&#160;&#160;Except as provided in Section 12.2.2,
      in the event of any transfer of title to the Premises by Landlord, the transferring Landlord shall thereafter be entirely freed and relieved from the performance and observance of all covenants and obligations hereunder, and Tenant shall only look to
      any subsequent party becoming Landlord hereunder the same. Tenant hereby agrees to enter into such agreements or instruments as may, from time to time, be requested in confirmation of the foregoing.</font></p>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="margin: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>IN WITNESS WHEREOF</b>, the parties hereto have duly
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>LANDLORD:</b></font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>2850 2855 &amp; 2859 GAZELLE OWNER (DE) <br>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">EXHIBIT A</font></p>
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  <p style="font: bold 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-transform: uppercase; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">LEGAL DESCRIPTION OF THE PREMISES</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TRACT ONE:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">PARCEL 1 OF MINOR SUBDIVISION NO. 2018-0009 IONIS CARLSBAD CAMPUS, IN THE CITY OF
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">INTENTIONALLY DELETED.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">INTENTIONALLY DELETED.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">TRACT THREE-A:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">INTENTIONALLY DELETED.</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">11.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Except for the Right of First Negotiation
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      trust deed holder or prospective purchaser or investor will be relying upon the statements contained herein in making the loan or acquiring the Premises, and in accepting an assignment of the Lease as collateral security, and that receipt by it of
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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      part hereof (the &#8220;<b>Leased Premises</b>&#8221;) pursuant to the terms, covenants and conditions of that certain Lease Agreement dated as of _____________, 20__ (the &#8220;<b>Lease</b>&#8221;). Capitalized terms used herein shall have the same meaning as set forth in
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      Memorandum of Lease</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">[to be attached]</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SUBORDINATION, NON-DISTURBANCE</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">WHEN RECORDED MAIL TO</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Morrison &amp; Foerster LLP</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">250 West 55th Street</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">New York, New York 10019</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Attention: Chris Delson</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">SPACE ABOVE THIS LINE FOR RECORDER'S USE</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center; border: Black 1.5pt solid"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>SUBORDINATION, NON-DISTURBANCE AND ATTORNMENT
        AGREEMENT</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">This SUBORDINATION, NON-DISTURBANCE AND ATTORNMENT
      AGREEMENT (hereafter referred to as "<u>Agreement</u>") made as of October&#160;________, 2022, by and between CR&#201;DIT AGRICOLE CORPORATE AND INVESTMENT BANK, having an address at 1301 Avenue of the Americas, New York, New York 10019, as administrative
      agent (with its successors and assigns, &#8220;Agent&#8221;) for itself and certain lenders now or hereafter party to the Loan Agreement (as hereinafter defined) (the "<u>Lenders</u>"), IONIS PHARMACEUTICALS, INC., a Delaware corporation, having an address of
      2855 Gazelle Ct., Carlsbad, CA 92008 ("<u>Tenant</u>") and 2850 2855 &amp; 2859 GAZELLE OWNER (DE) LLC, a Delaware limited liability company, having an address at c/o Oxford Properties Group, 450 Park Avenue, 9th Floor, New York, New York 10022 ("<u>Landlord</u>").</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">The Lenders have made a loan to Landlord in the maximum
      principal amount of $170,000,000.00 in accordance with the terms of that certain Loan Agreement dated as of October&#160;_______, 2022 (the "<u>Loan</u>"), by and among Landlord, Agent and Lenders (as the same may hereafter be amended, reinstated,
      extended, supplemented or otherwise modified from time to time, the "<u>Loan Agreement</u>"),</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Pursuant to the Loan Agreement, the Agent, for the benefit
      of the Lenders, is the holder of a certain Deed of Trust, Security Agreement, Assignment of Leases and Rents and Fixture Filing (as the same may be amended, extended, supplemented or otherwise modified or restated from time to time, the "<u>Security
        Instrument</u>") granted by Landlord to Agent, for the benefit of the Lenders, and recorded in the official records of San Diego County, California, which constitutes a first lien against the real property described on <u>Schedule A</u> attached
      hereto and the improvements thereon or to be constructed thereon (the "<u>Property</u>").</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Tenant has entered into a lease with Landlord dated as of
      October&#160;_______, 2022 (the "<u>Lease</u>") covering all of the Property (the "<u>Premises</u>"). All capitalized terms used but not defined in this Agreement shall have the meanings set forth in the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">For mutual consideration, including relying on the mutual
      covenants and agreements contained in this Agreement, the receipt and sufficiency of which are hereby acknowledged, Agent, Landlord and Tenant agree as follows:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Subordination of Lease</b>. Subject to the
      terms of this Agreement, the Lease and all of Tenant&#8217;s right, title, and interest in and to the Property thereunder (including, but not limited to, any option to purchase, right of first refusal to purchase, or right of first offer to purchase the
      Property or any portion thereof) is and shall be subject and subordinate to the Security Instrument and to all present and future advances under the obligations secured thereby and all renewals, amendments, modifications, consolidations, replacements
      and extensions thereof, to the full extent of the principal amount and other sums secured thereby and interest thereon, so that at all times the Security Instrument shall be and remain a lien on the Property prior to and superior to the Lease for all
      purposes, subject to the provisions set forth in this Agreement. Such subordination shall have the same force and effect as if the Security Instrument and such renewals, modifications, consolidations, replacements and extensions of the Security
      Instrument had been executed, acknowledged, delivered and recorded prior to the Lease, all amendments or modifications of the Lease, and any notice of the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Attornment</b>. Tenant will attorn to and
      recognize: (i) Agent (including for this purpose any transferee or nominee of Agent), whether as mortgagee in possession or otherwise; or (ii) any purchaser at a foreclosure sale under the Security Instrument; or (iii) any transferee that acquires
      possession of or title to the Property (whether by acceptance of a deed in lieu of foreclosure or otherwise); or (iv) any successors and assigns of such purchasers and/or transferees (each of the foregoing persons or entities described in clauses (i)
      through (iv) above, a "<u>Successor</u>"), as its landlord for the unexpired balance (and any extensions, if exercised) of the term of the Lease upon the terms and conditions set forth in the Lease (as affected by this Agreement), and Tenant shall
      pay and perform in favor of Successor all of the obligations of Tenant under the Lease as if Successor were the original lessor under the Lease. Such attornment shall be effective and self-operative without the execution of any further instruments by
      any party hereto; <u>provided</u>, <u>however</u>, that Tenant will, upon request by Agent or any Successor, execute a reasonable written agreement attorning to Agent or such Successor, which agreement shall, in any event, be subject to the terms
      and provisions of this Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Non-Disturbance</b>. So long as the Lease
      is in effect and Tenant complies with Tenant's obligations under this Agreement and is not in default (beyond the expiration of any applicable cure period) under the Lease, Agent and any Successor (i) will recognize the Lease and Tenant's rights and
      options under the Lease as the tenant of the Premises for the remainder of the term of the Lease (as affected by this Agreement), including any extension options, if exercised, and (ii)&#160;will not disturb Tenant's use, possession and quiet enjoyment of
      the Premises, nor will Tenant&#8217;s rights under this Lease be impaired (except as provided in this Agreement), and (iii)&#160;shall not name or join Tenant as a defendant in any foreclosure action, sale under a power of sale or transfer in lieu of the
      foregoing (collectively, a &#8220;<u>Foreclosure</u>&#8221;) unless a joinder is required by law to perfect a Foreclosure or other remedy, but then only for such purpose and not for the purpose of terminating the Lease.</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">68</font></div>
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  </div>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Assignment of Leases</b>. Tenant
      acknowledges that it has been advised that Landlord has assigned the Lease and the rents thereunder to Agent, for the benefit of the Lenders, pursuant to the Security Instrument. Tenant acknowledges that the interest of the Landlord under the Lease
      is to be assigned to Agent solely as security for the purposes specified in the Security Instrument, and, on account of the Security Instrument, Agent shall have no duty, liability or obligation whatsoever under the Lease or any extension or renewal
      thereof, either by virtue of the Security Instrument or by any subsequent receipt or collection of rents thereunder, unless Agent shall specifically undertake such liability in writing. The foregoing agreement by Tenant shall not adversely affect any
      rights of Tenant under the Lease with respect to the Landlord in the event of nonperformance by Landlord, subject to the terms of this Agreement. Tenant agrees that if Agent, pursuant to the Security Instrument, and whether or not it becomes a
      mortgagee in possession, shall give written notice to Tenant that Agent has elected to require Tenant to pay to Agent the rent and other charges payable by Tenant under the Lease, Tenant shall (without any duty to inquire as to the enforceability or
      validity of Agent&#8217;s notice) until Agent shall have canceled such election in writing, thereafter pay to Agent all rent and other sums payable under the Lease and such payments to Agent shall be treated as payments made under the Lease. Any such
      payment shall be made notwithstanding any right of setoff, defense or counterclaim which Tenant may have against Landlord, or any right to terminate the Lease. Landlord authorizes and directs Tenant to immediately and continuously make all such
      payments at the direction of Agent, releases Tenant of any and all liability to Landlord for any and all payments so made, and agrees that payments actually made by Tenant to Agent shall be credited towards the amounts due under the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Limitation of Liability</b>. In the event
      that Agent (including for this purpose any transferee or nominee of Agent) or any other Successor succeeds to the interest of Landlord under the Lease, or title to the Property, then none of Agent, any Lender or any Successor shall be: (i) liable in
      any way to Tenant for any act or omission, neglect or default on the part of any prior landlord under the Lease; <u>provided</u>, that, nothing in this clause being deemed to relieve Agent or any Successor of an ongoing default on the part of
      Landlord with respect to repair and maintenance of the Premises that first arose prior to such succession, provided that Tenant notified Agent of such default in accordance with Section&#160;7 of this Agreement and Agent failed to cure same, and Agent or
      any Successor shall have the obligation to cure such ongoing repair and maintenance defaults on the part of Landlord that continue from and after Successor succeeds to the rights of Landlord under the Lease, regardless of when such default or
      obligation from arose, provided that Tenant notified Agent of such default in accordance with Section&#160;7 of this Agreement and Agent failed to cure same; (ii) responsible for any monies (including security deposits) owing by or on deposit with (or any
      letter of credit on deposit with) Landlord to the credit of Tenant (except to the extent any such deposit or letter of credit is actually received by Agent or such Successor, as applicable); (iii) subject to any defense, counterclaim or setoff which
      theretofore accrued to Tenant against any prior landlord; provided, however, that the foregoing shall not limit Tenant&#8217;s right to exercise against Agent or such Successor any offset right otherwise available to Tenant because of events occurring
      after the date of succession and attornment; (iv) bound by any termination, amendment or modification, or assignment/subletting of the Lease after the date hereof (unless Agent expressly approved in writing such termination, amendment or
      modification, or assignment or subletting or the same does not require the Agent&#8217;s approval pursuant to the terms of the Loan Agreement) of the Lease (provided that, (A) as it relates to any assignments/subletting of Lease undertaken in connection
      with the terms and provisions set forth in the Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (B) no such approval shall be required with respect to amendments solely evidencing the exercise of Tenant&#8217;s
      option to extend the Lease and assignments or sublets that do not require the consent of the Landlord pursuant to the terms of the Lease); (v) bound by any previous prepayment of rent for more than one (1) month of the date due, which was not
      approved in writing by Agent; (vi) required after a fire, casualty or condemnation of the Property or Premises to repair or rebuild the same to the extent that such repair or rebuilding requires funds in excess of the insurance or condemnation
      proceeds specifically allocable to the Premises and arising out of such fire, casualty or condemnation which have actually been received by Agent, and then only to the extent required by the terms of the Lease (Agent acknowledging that the exercise
      by Tenant of its remedies pursuant to Article 9 of the Lease are unaffected by the provisions of this clause (vi)), (vii) be liable for or incur any obligation with respect to any representations or warranties made by Landlord under the Lease; (viii)
      liable beyond Agent&#8217;s, such Lender&#8217;s, or such Successor's, as applicable, interest in the Property and in the rents, proceeds and profits therefrom; or (ix) responsible for any obligation of Landlord to undertake or complete any work or fund any
      allowance for tenant improvements.</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">69</font></div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Purchase Rights</b>. Each of the parties
      hereto acknowledges that pursuant to the Lease, Tenant holds a right of first offer to purchase the property pursuant to Article 11 of the Lease (the &#8220;<u>Purchase Rights</u>&#8221;). The parties hereto agree that the Purchase Rights shall remain valid and
      in full force and effect, but subject and subordinate to the lien(s) of the Security Instrument. In the event that Agent or a Successor succeeds to the interest of Landlord under the Lease, such Purchase Rights shall not be extinguished by a
      Foreclosure; provided, however, that Agent or Successor shall not be bound to the Purchase Rights, and such Purchase Rights shall not apply, with respect to (i)&#160;a Foreclosure, including, without limitation, the granting of, foreclosure under, or
      giving of a deed-in-lieu of foreclosure under, a mortgage or the granting or exercise of any pledge of ownership interests, or (ii) the first subsequent sale of the Property following Agent&#8217;s or Successor&#8217;s acquisition of title to the Property, but
      thereafter any, successor landlord to Agent or such Successor shall be bound by such Purchase Rights in accordance with the terms of the Lease.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>7.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Right to Cure Defaults</b>. Tenant agrees
      to give to Agent, either by certified U.S. mail (return receipt requested) or overnight courier service (i.e., FedEx), a duplicate of each notice of any default by Landlord under the Lease at the time Tenant gives such notice to Landlord, specifying
      the nature of such default, and thereupon Agent shall have the right (but not the obligation) to cure such default, and Tenant shall not exercise its remedies under the Lease unless the Tenant first gives such notice to Agent and provides Agent with
      notice of such default, and an opportunity to cure the same within a period of time that shall be not less than the period of thirty (30) days beyond any period afforded to the Landlord to cure the default under the provisions of the Lease, and a
      reasonable period of time in addition thereto (i) if the circumstances are such that said default cannot reasonably be cured within such period and Agent has commenced and is diligently pursuing such cure, plus (ii<b>) </b>a reasonable period (not
      to exceed 270 days unless the cure cannot be effected without Agent taking possession of the Property) during any litigation or enforcement action or proceeding, including a foreclosure, bankruptcy, reorganization, possessory action or a combination
      thereof provided that Agent or any Successor provides Tenant with written notice of its intent to cure such default and then proceeds diligently to cure Landlord&#8217;s default upon acquiring possession of the Premises. It is specifically agreed that
      Tenant shall not exercise its remedies under the Lease against Agent or any Successor for failure to cure any bankruptcy, insolvency or reorganization default on the part of Landlord, any breach by Landlord of any representation or warranty, or any
      other breach or default under the Lease that is personal to Landlord or otherwise not reasonably susceptible of cure by Agent or such Successor. Tenant shall accept performance by Agent of any term, covenant, condition or agreement to be performed by
      Landlord under the Lease with the same force and effect as though performed by Landlord. Without limitation on the foregoing, if the Lease is terminated for any reason other than (a)&#160;a termination which is effected unilaterally by Tenant in
      accordance with the express terms of the Lease, (b)&#160;the expiration of the term of the Lease, or (c)&#160;a termination that occurs in compliance with this Agreement, then upon Agent&#8217;s written request given within thirty (30) days after Agent receives
      written notice of such termination, Tenant shall, within fifteen (15) days after such request, execute and deliver to Agent a new lease of the Premises for the remainder of the term of the Lease, such new lease to be upon all of the same terms,
      covenants and conditions of the Lease applicable to the remainder of the term of the Lease (as affected by this Agreement).</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>8.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Tenant's Agreements</b>. Tenant hereby
      represents, warrants, covenants and agrees that: (i)&#160;Tenant shall not pay any rent under the Lease more than one month in advance of the date due except as expressly required in the Lease with respect to security deposits, operating expenses, taxes
      and the like; (ii)&#160;Tenant shall have no right to appear in any Foreclosure action under the Security Instrument (unless named by Agent in such action, Agent agreeing however not to name Tenant unless required pursuant to applicable laws, and then
      only for such purposes); (iii) Tenant shall not amend or modify, or assign or sublet, the Lease and Tenant shall have no right to cancel or terminate the Lease, without Agent&#8217;s prior written consent (provided that, (x) as it relates to any
      assignments/subletting of Lease undertaken in connection with the terms and provisions set forth in the Lease, Agent shall have the same approval rights as the Landlord has with respect to same and (y) no such approval shall be required with respect
      to amendments solely evidencing the exercise of Tenant&#8217;s option to extend the Lease and assignments or sublets that do not require the consent of the Landlord pursuant to the terms of the Lease), and any attempted amendment or modification,
      assignment or subletting, cancellation or termination of the Lease in violation of the foregoing shall be of no force or effect as to Agent; (iv) Tenant shall not subordinate the Lease to any lien or encumbrance (other than the Security Instrument)
      without Agent&#8217;s prior written consent; (v) except as expressly set forth in Section 6, above, Tenant has no right or option of any nature whatsoever, whether pursuant to the Lease or otherwise, to purchase the Property, or any portion thereof or any
      interest therein, and to the extent that Tenant hereafter acquires any such additional rights or options, the same is hereby acknowledged to be subject and subordinate to the Security Instrument and is hereby waived and released as against Agent and
      any Successor, (vi)&#160;Tenant shall promptly, to the same extent and within the same time period required by the Lease, deliver to Agent, from time to time, a written estoppel statement in the form, and with the certifications, required by the Lease;
      (vii) this Agreement supersedes and satisfies any requirement in the Lease relating to the granting of a non-disturbance agreement or providing for subordination of the Lease; (viii)&#160;Tenant is the sole owner of the leasehold estate created by the
      Lease; (ix)&#160;the interest of Landlord under the Lease is assigned to Agent solely as security for the obligations secured by the Security Instrument, and neither Agent nor the Lenders shall have any duty, liability or obligation under the Lease or any
      extension or renewal thereof, unless Agent either (a) specifically undertakes such liability in writing, or (b) subject to the express terms of this Agreement, Agent becomes a Successor; (x) if this Agreement conflicts with the Lease, then this
      Agreement shall govern as between the parties and any Successor, including upon any attornment pursuant to this Agreement; and (xi)&#160;upon Agent&#8217;s transfer or assignment of Agent&#8217;s interests in the Loan, the Lease (or any new lease executed pursuant to
      this Agreement), or the Property, Agent shall be deemed released and relieved of any obligations under this Agreement, the Lease (or any new lease executed pursuant to this Agreement), and with respect to the Property.</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>9.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Authority</b>. Each of Landlord, Agent,
      and Tenant warrants and represents to the other parties hereto that it has duly executed and delivered this Agreement and that the execution, delivery and performance by it of this Agreement (i) are within the its powers, (ii) have been duly
      authorized by all requisite action, and (iii) do not violate any provision of law or any order of any court or agency of government, or any agreement or other instrument to which it is a party or by which it or any of its property is bound.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>10.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Miscellaneous</b>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Section 10.1&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>The provisions hereof shall be
      binding upon and inure to the benefit of Tenant and Agent and their respective successors and assigns, the term "Agent" as used herein includes any successor or assign of the named Agent herein, and the terms "Tenant" and "Landlord" as used herein
      include any successor and assign of the named Tenant and Landlord herein, respectively; provided, however, that such reference to Tenant's or Landlord's successors and assigns shall not be construed as Agent's consent to any assignment or other
      transfer by Landlord in any instance where Agent&#8217;s consent to such assignment or transfer is required hereunder, under the Security Instrument or under any other document executed in connection therewith.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Section 10.2&#160;&#160;&#160;&#160;&#160;&#160;&#160; </b>Any notices, demands or
      requests to be given under this Agreement shall be in writing and shall be deemed sufficiently given if served personally or upon the first to occur of receipt or the refusal of delivery if mailed by United States certified mail, return receipt
      requested, postage prepaid, or if sent by prepaid Federal Express or other similar overnight delivery service which provides a receipt, addressed to the Primary Address of Landlord, Tenant or Agent set forth below, along with copies to the applicable
      Supplemental Addresses set forth below, or such other address as such party may specify in writing from time to time;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>If to Tenant</u></b>:1</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Primary Address</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">__________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Supplement Addresses</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">__________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1 NTD:&#160;&#160;Tenant contact info to be provided</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>If to Landlord</u></b>:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Primary Address</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">450 Park Avenue, 9th Floor</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">New York, New York 10022</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Attention: Legal Department</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Supplement Addresses</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">33 Arch Street, 26th Floor</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Boston, Massachusetts 02110</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Attention: John L. Sullivan</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>If to Agent</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b><u>Primary Address</u></b>:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cr&#233;dit Agricole Corporate and Investment Bank</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1301 Avenue of the Americas</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">New York, New York 10019</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">New York, New York 10019</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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      a Delaware limited liability company, whose address is [________________] (&#8220;<b><i>Ionis</i></b>&#8221;). Prospective Purchaser and Ionis are sometimes referred to individually as a &#8220;<b><i>Party</i></b>&#8221; and collectively as the &#8220;<b><i>Parties</i></b>&#8221;.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>RECITALS</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">WHEREAS, Ionis currently leases and occupies that certain
      real property located at 2850, 2855 &amp; 2859 Gazelle Court, Carlsbad, California, 92010 (the &#8220;<b><i>Property</i></b>&#8221;) pursuant to that certain Lease Agreement dated as of [_______________], 2022 (the &#8220;<b><i>Lease</i></b>&#8221;), by and between Ionis
      and 2850 2855 &amp; 2859 Gazelle Owner (DE) LLC, a Delaware limited liability company (&#8220;<b><i>Landlord</i></b>&#8221;);</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      evaluation of a purchase of the Property, and (ii) Prospective Purchaser&#8217;s actions as landlord under the Lease, if Ionis shall continue to lease and occupy the Property and in the event Prospective Purchaser purchases the Property (collectively, the
      &#8220;<b><i>Purpose</i></b>&#8221;), Prospective Purchaser may enter the Property and may gain access to materials and information and observe processes which are non-public, confidential or proprietary in nature; and</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">WHEREAS, the Parties recognize the critical importance of
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      becoming Ionis&#8217; landlord under the Lease.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Confidential Information</u>. Except as set
      forth in <u>Section 2</u> below, &#8220;<b><i>Confidential Information</i></b>&#8221; means all non-public, confidential or proprietary information (i) disclosed by or on behalf of Ionis, its Affiliates, or their respective agents, or employees (collectively,
      the &#8220;<b><i>Ionis Parties</i></b>&#8221;) to Prospective Purchaser, its Affiliates and subcontractors, or their respective agents, employees, or advisors, or any other person or entity providing the services by and through Prospective Purchaser
      (collectively, the &#8220;<b><i>PTP Parties</i></b>&#8221;), whether disclosed orally or in written, electronic or other form or media, and whether or not marked, designated or otherwise identified as &#8220;confidential,&#8221; (ii) observed by any of the PTP Parties in
      entering on to the Property and (iii) as may be observed or obtained by Prospective Purchaser in the course of acting as landlord under the Lease (should Prospective Purchaser purchase the Property and Ionis shall continue to lease and occupy the
      Property pursuant to the Lease), including, without limitation, Trade Secret Information, any information that would reasonably be considered non-public, confidential or proprietary given the nature of the information and the Ionis Parties&#8217;
      businesses and all notes, analyses and other materials prepared by or for the Purpose that contain any of the foregoing. As used in this Agreement, &#8220;<b><i>Trade Secret Information</i></b>&#8221; means all information that is unique to Ionis&#8217; business and
      that is not commonly known by or available to the public or otherwise known through Prospective Purchaser&#8217;s business and that: (i) derives or creates economic value for Ionis&#8217; business, actual or potential, from not being generally known to, and not
      being readily ascertainable by proper means by, other persons who can obtain economic value from its disclosure or use; and (ii) is the subject of efforts that are reasonable under the circumstances to maintain its secrecy. The Ionis Parties&#8217; Trade
      Secret Information may include, but is not limited to, all confidential information relating to Ionis&#8217; business and operations and in the form of the Ionis Parties&#8217; research and development plans and activities; design plans; compilations of data;
      product plans; inventions; engineering processes and activity; manufacturing plans, processes and activity; proprietary computer software and programs (including object code and source code); and proprietary computer and database technologies,
      systems, structures, and architectures.</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;at the time of disclosure is, or thereafter
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;at the time of disclosure is, or thereafter
      becomes, available to Prospective Purchaser on a non-confidential basis from a third-party source, provided that such third-party is not and was not, to Prospective Purchaser&#8217;s knowledge, prohibited from disclosing the information to Prospective
      Purchaser by any legal, fiduciary or contractual obligation;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;was known by or in the possession of
      Prospective Purchaser prior to being disclosed by or on behalf of the Ionis Parties pursuant to this Agreement;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;was independently developed by Prospective
      Purchaser without reference to or use of, in whole or in part, any Confidential Information; or</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Ionis has agreed in writing is free of such
      obligations.</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Confidential Information and Other Property
        of the </u>Ionis <u>Parties</u>. All Confidential Information shall be deemed the property of the Ionis Parties. All information, documents, and electronic media (including, but not limited to Confidential Information) furnished by or on behalf
      of the Ionis Parties to the Prospective Purchaser shall be the property of the Ionis Parties.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">4.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Prospective Purchaser Obligations</u>.
      Prospective Purchaser shall:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;protect the Confidential Information from
      unauthorized disclosure and use, with at least the same degree of care as the Prospective Purchaser would use in protecting its own confidential information, but no less than a commercially reasonable degree of care;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not use the Confidential Information, or permit
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not disclose the Confidential Information to
      any person or entity, including, without limitation, to any of the PTP Parties, except to PTP Parties who: (i) need to know the Confidential Information to assist Prospective Purchaser, or act on its behalf, in relation to the Purpose; (ii) are
      informed by Prospective Purchaser of the confidential nature of the Confidential Information (each an &#8220;<b><i>Authorized Party</i></b>&#8221;) (Prospective Purchaser acknowledging that a breach of this Agreement by a PTP Party shall be treated as a breach
      of this Agreement by Prospective Purchaser);</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not use any of the Ionis Parties&#8217; computers,
      computer systems, equipment, tools, or other property of the Ionis Parties without Ionis Parties&#8217; consent;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not use any Confidential Information to compete
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;upon Ionis&#8217; written request, destroy or
      deliver promptly to Ionis, or Ionis&#8217; designee, all Confidential Information (including all copies thereof, regardless of the medium in which such information may be stored) and all computers, equipment, tools, and other property of the Ionis Parties
      that happen to be in Prospective Purchaser&#8217;s possession;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;promptly notify Ionis upon discovery of any
      unauthorized disclosure of Confidential Information caused by Prospective Purchaser and reasonably cooperate with Ionis in any effort undertaken by Ionis to enforce its rights related to any such unauthorized disclosure;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;not record in any form, including by hand,
      video or audio, any Trade Secret Information observed on the Property, without Ionis&#8217; written consent;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;be responsible if any provisions of this
      Agreement are violated by any Authorized Party;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(j)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;at all times while on the Property be
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(k)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;at all times while on the Property follow all
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Prospective Purchaser Representations and
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the performance of its obligations herein does
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;unless and until becoming landlord under the
      Lease (as and to the extent Ionis continues to lease and occupy the Property pursuant to the Lease), it is entering upon the Property for the sole purpose of evaluating a potential purchase of the Property.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Ionis Representations or Warranties;
        Disclaimer of Liability</u>. The Ionis Parties make no representation or warranty, express or implied, as to the accuracy or completeness of the Confidential Information disclosed to Prospective Purchaser hereunder. The Ionis Parties shall not be
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      recognizes, acknowledges and agrees that Ionis shall be entitled to seek all of the civil remedies provided by federal, state and local law, including without limitation, preliminary and permanent injunctive relief restraining Prospective Purchaser
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT H</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">The plans and specifications prepared by DGA | Planning | Architecture |
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      Construction Documents dated 5/17/2022, and Plan Check Resubmittal #1 dated 6/16/2022, copies of which are on file with Landlord.<br style="clear: both">
    </font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT I</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">[***]</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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        <td style="width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Name:</font></td>
        <td style="border-bottom: Black 1pt solid; width: 45%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</font></td>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: center; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>EXHIBIT K</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: center; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>TENANT CONSTRUCTION MANUAL</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>[Attached]</b></font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="color: #44546A; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <p style="color: #44546A; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <p style="color: #44546A; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><i>Tenant Construction Manual</i></font></p>
  <p style="color: #44546A; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><i>&#160;</i></font></p>
  <p style="color: #8EB3CE; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Section 1: GENERAL INFORMATION</font></p>
  <p style="color: #8EB3CE; font: 18pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="width: 31.5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">1.01</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Introduction</font></td>
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  <p style="color: #44546A; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"></p>
  <p style="color: #44546A; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">These Construction Rules and Regulations been prepared to introduce Tenants and
      Contractors to the Oxford Properties Group Design, Systems and Building Regulations in order to assist in the design and construction of the leased premises. These Rules and Regulations are to be read in conjunction with the building lease document.
      In the event of any conflict between these Rules and Regulations and the lease, the provisions of the lease or any other specific written agreements between the Landlord and Tenant shall prevail.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Subject to the preceding paragraph, the Landlord reserves the right, from time to time, to
      add to or amend the information, procedures and regulations contained herein in a reasonable manner consistent with similar single tenant NNN facilities in the Carlsbad, California area and the Lease, upon reasonable prior notice to Tenant. Any such
      additions or amendments will affect any Construction work undertaken after the addition or amendment has been issued.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 31.5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C">1.02</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C">Tenant Coordination</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      within the Landlord's organization. All questions, comments and submissions are to be addressed to:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 48.45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Oxford Properties Group</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_____________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">_____________</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 183.75pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 31.5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C">1.03</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C">Tenant Design and Working Drawings</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      PDF and CAD ver. 14 or later and three (3) sets of Tenant Design Working Drawings and Specifications of all work proposed within the Leased premises. The landlord requires that drawing packages are provided in the following stages:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 78.55pt; text-indent: -0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">-&#160;&#160;&#160;&#160;&#160;&#160; Building Permit submission</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 78.55pt; text-indent: -0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">-&#160;&#160;&#160;&#160;&#160;&#160; Issued for Construction Submission</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 78.55pt; text-indent: -0.25in"></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 78.55pt; text-indent: -0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">-&#160;&#160;&#160;&#160;&#160;&#160; As-built drawings as further outlined in the Lease</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 78.55pt; text-indent: -0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      drawings have been reviewed the Landlord will forward an approval letter to the Tenant outlining any comments or changes, if any, that pertain to the drawings. The drawings may be subject to change if requested. Revised drawings are to include all
      the comments and corrections and a set of prints provided prior to commencing work. Drawings to be resubmitted shall be revised to conform to the requirements and re-submitted for subsequent Landlord review. Any revisions to the Landlord reviewed
      drawings must be submitted for further review, and work must not proceed until the revised drawings are returned to the contractor. A Copy of the Landlord reviewed drawings must be kept on the job site for viewing throughout the construction period.
      Landlord shall respond to requests for approval as provided in the Lease.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Additional or expanded information, for purposes of definition or clarification before
      giving approval may be required. Working drawings should supply the information listed below (depending on the stage).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"> 1.03.01 <b><i>Complete Floor Plans (drawing scale of 1/8" = 1')</i></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 5.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">a)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Location of all major fixed elements within the leased premises dimensionally related to grid lines and demising partitions.</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">b)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Location and layout of rooms of unusual loading concentrations such as cranes, racking areas and calculations of unusual loadings which may result in floor
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">c)</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">d)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Floor materials and finishes throughout the premises.</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">e)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Location of exit lights.</font></td>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"> 1.03.02 <b><i>Complete Reflected Ceiling Plans (scale: 1/8" = 1&#8217;)</i></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 5.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt; text-indent: 30.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"> 1.03.03 <b><i>Complete Construction Details</i></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 5.6pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt; text-indent: 30.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">These plans should be appropriately scaled and indicate methods of
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 41.6pt; text-indent: 30.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Details of all metering equipment changes to conform to base building standards. Schedule
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 45pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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            all permits must be delivered to the Landlord. The Tenant must correct immediately any work, which does not meet with the approval of the building inspector, even though the Tenants drawings may have been reviewed previously by the appropriate
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C"><b>2.08</b></font></td>
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  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.25pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; color: #80BE8C; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C"><b>2.09</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.4pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.4pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      <tr style="vertical-align: top">
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        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C"><b>2.10</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.55pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      <tr style="vertical-align: top">
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        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C"><b>2.11</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 13.6pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 15.15pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 15.15pt 0pt 0"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; color: #80BE8C; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0pt"></td>
        <td style="width: 0.75in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: #80BE8C"><b>2.12</b></font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.35pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      <tr style="vertical-align: top">
        <td style="width: 0pt"></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 2.35pt 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

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        <td style="width: 0.75in"></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.75in"></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">&#160;</p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Landlord requires all contractors and subcontractors performing work at the Property to carry
      insurance. Property Management collects certificates of insurance, which contain information about the vendor&#8217;s insurance. This insurance must meet certain minimum requirements and name Landlord, Oxford Properties Group, Arcadia Management Group,
      Inc., and Oxford I Asset Management US as additional insureds.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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      <tr style="vertical-align: top">
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      contracts related to the work, broad form property damage (including completed operations), independent contractors&#8217; protective, personal injury liability, automobile liability comprehensive form for owned, hired and non-owned vehicles, elevators and
      escalators hazards, and incidental medical malpractice coverage hazards, and as follows: combined single limits for (i) bodily injury and (ii) property damages, endorsed such that the policy aggregate applies to each property location where work
      occurs. Bodily injury shall include, without limitation, damages for care and loss of services because of bodily injury, including death at any time resulting therefrom, sustained by any person or persons. Property Damage Liability Insurance shall
      include, without limitation, losses due to damages to or destruction of tangible property, including loss of use of such property resulting therefrom in compliance with the amounts set forth above; Contractor shall provide X, C and U coverage if
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
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        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">4.</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5.</font></td>
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">6.</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Property: </b>Property Insurance will cover the physical loss, including theft, or damage to equipment, machinery, supplies or tools owned, leased,
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">7.</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Professional Liability (Errors and Omissions): </b>If the nature of the work involves a professional liability exposure (e.g. design/build), contractor
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">8.</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Contractors Pollution - Asbestos Legal Liability: </b>If the nature of the services performed involves pollutants or any other materials which would
            affect soil, water or structures, then the contractor shall maintain contractors pollution &#8211; asbestos legal liability coverage for a limit of not less than $1,000,000 each occurrence - $2,000,000 policy aggregate, including errors and
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Certificate Holders, Additional Insured&#8217;s, and Additionally Insured Endorsement</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>CERTIFICATE OF INSURANCE LIMITS REQUIREMENT</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1.</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">For insurance requirements for crane lifts or any special contract work; contact for the property team for specific coverage and language.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2.</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Commercial General Liability Coverage Required (millions, per occurrence and aggregate) is the sum of the basic coverage + excess umbrella.</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">See Example for Electrical Maintenance below:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#9679;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Commercial General Liability Coverage Required = 5MM. This requirement is met by:</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#9679;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">General Liability each Occurrence 3MM + Excess umbrella 2MM = 5MM</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
        <td style="width: 0.25in"></td>
        <td style="width: 0.25in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#9679;</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">General Liability General Aggregate 3MM + Excess umbrella 2MM = 5MM</font></td>
      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif"><font style="font: 10pt Times New Roman, Times, Serif; color: Black">&#160;</font></p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
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  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Certificate of Insurance Limits</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: bottom; background-color: rgb(255,255,204)">
        <td style="width: 24%; border: Black 1pt solid; text-align: center; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Type of Service</b></font></td>
        <td style="width: 17%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>General Liability </b><br>
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        <td style="width: 21%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Employers&#8217; Liability </b><br>
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            <b>&#8211; Each Employee / </b><br>
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        <td style="width: 19%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Automobile </b><br>
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        <td style="width: 19%; border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Excess / Umbrella </b><br>
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      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Alarm Systems Service and Repair</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Appliance Repair &amp; <br>
            Maintenance</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Architectural <b>*</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Asbestos Abatement and Hazardous Material Removal <b>****</b></font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM / 5MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Audio-Visual Equipment</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Backflow Testing</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM/1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Cabling</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Carpet/Floor Finishes</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Crane/Rigging</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM / 5MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Custom Fabrication &amp;
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        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Doors &amp; Locks</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Electrical Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Elevator/Escalator Service &amp;
            Maintenance</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM / 5MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Elevator interior installation</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Engineering Consulting Service<b>*</b></font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fire Extinguishing in Restaurants</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Fitness Equipment Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Garbage Removal &amp; Disposal,
            incl. dumpster maintained on premises</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">General Contractors</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Generator Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Glass Repair &amp; Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Glass Repair &amp; Maintenance
            elevated</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM / 5MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Graffiti Removal</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>

  </table>
  <p style="margin: 0">&#160;</p>
  <p style="margin: 0">&#160;</p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: bottom; background-color: rgb(255,255,204)">
        <td style="border: Black 1pt solid; text-align: center; width: 24%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Type of Service</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 17%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>General Liability </b><br>
            <b>Each Occurrence / </b><br>
            <b>General Aggregate</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 21%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Employers&#8217; Liability </b><br>
            <b>Each Accident / Disease </b><br>
            <b>&#8211; Each Employee / </b><br>
            <b>Disease &#8211; Policy Limit</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 19%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Automobile </b><br>
            <b>Liability </b><br>
            <b>Combined </b><br>
            <b>Single Limit</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 19%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Excess / Umbrella </b><br>
            <b>Liability Each </b><br>
            <b>Occurrence / Aggregate</b></font></td>
      </tr>

  </table>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; width: 24%; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Handyman</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 17%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 21%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 19%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 19%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Heating, Ventilation &amp; Air
            Conditioning Service/install</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Insulation/Fiberglass</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Interior Design Consulting<b>*</b></font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Life Safety/Fire Equipment</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Life Safety/Monitoring</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Lighting re-lamping (interior)</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Elevated Lighting Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM /5MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Moves/Relocations/ reconfiguration</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Office Equipment Service</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Overhead and Revolving Door</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Painting</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Parking Surface Maintenance/sweeping</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0"></p>
        </td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM / 2MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Paving and Striping</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Plumbing</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Power washing (non-elevated)</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Power washing (elevated)</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM /5MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Pump Maintenance</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Roofing</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM /5MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Signage non elevated</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM / 2MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Signage Elevated</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">5MM / 5MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="vertical-align: top; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">10MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Sprinkler System Service and Repair</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Stonework/Marble/wood/ metal
            cleaners and refinishers Repair &amp; Maintenance</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM / 2MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>
      <tr style="vertical-align: top">
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; border-left: Black 1pt solid; padding-left: 5.4pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">Telecommunications and TV Equip.
            Master Wiring and Antennas (non-elevated)</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">3MM / 3MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">1MM</font></td>
        <td style="border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black">2MM</font></td>
      </tr>

  </table>
  <p style="margin: 0">&#160;</p>
  <p style="margin: 0">&#160;</p>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <div style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt" class="BRPFPageBreakArea">
    <div style="TEXT-ALIGN: center" class="BRPFPageNumberArea"><font style="FONT-SIZE: 10pt; FONT-FAMILY: 'Times New Roman', Times, serif; FONT-WEIGHT: normal; COLOR: #000000; FONT-STYLE: normal">&#160;</font></div>
    <div style="PAGE-BREAK-AFTER: always" class="BRPFPageBreak">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="FONT: 10pt Times New Roman, Times, Serif; MARGIN: 0pt 0px">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: bottom; background-color: rgb(255,255,204)">
        <td style="border: Black 1pt solid; text-align: center; width: 24%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Type of Service</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 17%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>General Liability </b><br>
            <b>Each Occurrence / </b><br>
            <b>General Aggregate</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 21%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Employers&#8217; Liability </b><br>
            <b>Each Accident / Disease </b><br>
            <b>&#8211; Each Employee / </b><br>
            <b>Disease &#8211; Policy Limit</b></font></td>
        <td style="border-top: Black 1pt solid; border-right: Black 1pt solid; border-bottom: Black 1pt solid; text-align: center; width: 19%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; color: Black"><b>Automobile </b><br>
            <b>Liability </b><br>
            <b>Combined </b><br>
            <b>Single Limit</b></font></td>
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            <b>Liability Each </b><br>
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<TYPE>EX-10.27
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<DESCRIPTION>EXHIBIT 10.27
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  <p style="font: 11pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 1in; text-align: center; text-indent: -1in">&#160;<b>&#160;</b></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif"><b>CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT HAVE BEEN OMITTED AND REPLACED WITH &#8220;[***]&#8221;. SUCH IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE
      IT IS BOTH (I) NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.</b></p>
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  <p style="font: bold 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>DEFEASANCE PLEDGE AND SECURITY AGREEMENT</u></font></p>
  <p style="font: bold 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>THIS DEFEASANCE PLEDGE AND SECURITY AGREEMENT </b>(this
      &#8220;<b>Agreement</b>&#8221;) dated as of October 20, 2022 is made by and among <b>IONIS GAZELLE, LLC</b>, a Delaware limited liability company (&#8220;<b>Original Borrower</b>&#8221;), <b>WELLS FARGO BANK, NATIONAL ASSOCIATION, AS TRUSTEE FOR THE BENEFIT OF THE
        REGISTERED HOLDERS OF UBS COMMERCIAL MORTGAGE TRUST 2017-C3, COMMERCIAL MORTGAGE PASS-THROUGH CERTIFICATES, SERIES 2017-C3</b>, as secured party (said Trustee or its successors and assigns, &#8220;<b>Lender</b>&#8221;), and, for the sole purpose of agreeing to
      the provisions of <b><u>Sections&#160;6(a)(viii), 7, 8, 9(b), 12, 14, 15, 16, 22, 25 and 26</u></b> of this Agreement, <b>U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION</b>, a national banking association, as Securities Intermediary and Custodian
      (together with its successors and assigns, &#8220;<b>Intermediary</b>&#8221;).</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>RECITALS:</b></font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">A.&#160;&#160;&#160;&#160;&#160;&#160;&#160;UBS AG, by and through its branch office at
      1285 Avenue of the Americas, New York, New York (&#8220;<b>Original Lender</b>&#8221;), made a loan (the &#8220;<b>Mortgage Loan</b>&#8221;) to Original Borrower in the original principal amount of $51,350,000.00, made pursuant to a Loan Agreement dated July 18, 2017 (the &#8220;<b>Loan
        Agreement</b>&#8221;), and evidenced by (1) a Promissory Note A-1 dated July 18, 2017 in the original principal amount of $36,350,000.00 (the &#8220;<b>Note A-1</b>&#8221;), (2) a Promissory Note A-2 dated July 18, 2017 in the original principal amount of
      $5,000,000.00 (the &#8220;<b>Note A-2</b>&#8221;), and (3) a Promissory Note A-3 dated July 18, 2017 in the original principal amount of $10,000,000.00 (Note A-1, Note A-2 and Note A-3 are, individually and collectively, the &#8220;<b>Note</b>&#8221; or the &#8220;<b>Notes</b>&#8221;).</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Mortgage Loan and the Notes are secured
      by, among other things, a Deed of Trust and Security Agreement dated July 18, 2017 from Original Borrower to and for the benefit of Original Lender (the &#8220;<b>Security Instrument</b>&#8221;), which grants to Original Lender, among other things, a lien on the
      real and personal property described in said Security Instrument (the &#8220;<b>Mortgaged Property</b>&#8221;). The Mortgage Loan is further evidenced or secured by various other documents, including guaranties, executed by Original Borrower and others in favor
      of Original Lender (together with the Notes, the Loan Agreement and the Security Instrument, the &#8220;<b>Mortgage Loan Documents</b>&#8221;).</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">C.&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Lender assigned all of its right,
      title and interest in the Mortgage Loan and the Mortgage Loan Documents (by one or more assignments) to Lender in connection with the issuance of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3
      (the &#8220;<b>Certificates</b>&#8221;). Lender is the current holder of the Notes and the owner of the Mortgage Loan and the Mortgage Loan Documents.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">D.&#160;&#160;&#160;&#160;&#160;&#160;&#160;Midland Loan Services, a division of PNC Bank,
      National Association (&#8220;<b>Servicer</b>&#8221;), is the Master Servicer under the Pooling and Servicing Agreement dated as of August 1, 2017 (as from time to time amended, supplemented or modified, the &#8220;<b>Pooling and Servicing Agreement</b>&#8221;).</font></p>
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      Original Borrower has directed Lender to release the Mortgaged Property and all escrows and reserves from the liens and security interests of the Security Instrument and to release any other collateral or security previously given by Original
      Borrower as security for the Mortgage Loan upon Original Borrower&#8217;s defeasance of the Mortgage Loan (the &#8220;<b>Defeasance</b>&#8221;).</font></p>
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      on the Mortgaged Property is that Original Borrower grant a security interest in the Pledged Collateral (as defined herein) to Lender to secure the payment and performance in full when due of all amounts payable under the Mortgage Loan Documents.</font></p>
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      execution of this Agreement, Lender, Servicer, Original Borrower, DHC UBSCM 17 C3 Successor Borrower-R, LLC, a Delaware limited liability company (&#8220;<b>Successor Borrower</b>&#8221;), and Intermediary will enter into the Defeasance Assignment, Assumption
      and Release Agreement of even date herewith (the &#8220;<b>Defeasance Assumption Agreement</b>&#8221;) pursuant to which, among other things, Original Borrower will transfer the Pledged Collateral to Successor Borrower and, to the extent set forth in the
      Defeasance Documents, Successor Borrower will assume the rights and obligations of Original Borrower under the Note, this Agreement and the Account Agreement.</font></p>
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      and sufficiency of which are hereby acknowledged, Original Borrower, Lender, and (as to the provisions specified in the first paragraph of this Agreement) Intermediary agree as follows:</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;1.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Definitions</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The following terms shall have the following meanings
      when used herein. Each capitalized term used and not defined herein shall have the meaning assigned to such term in the Mortgage Loan Documents.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Account Agreement</b>&#8221; means the Defeasance Account
      Agreement of even date herewith among Original Borrower, Lender, Servicer, Intermediary, and Account Bank.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Accountant&#8217;s Report</b>&#8221; means that certain
      Defeasance Report of even date herewith from Causey Demgen &amp; Moore P.C. regarding the Defeasance, a copy of which is attached hereto as <b><u>Exhibit&#160;B</u></b>.</font></p>
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          16</u></b> herein.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Book-Entry Securities</b>&#8221; means U.S. Obligations
      that are (a)&#160;&#8220;Book-Entry Securities&#8221; as defined in 31&#160;C.F.R. Section 357.2, that have been issued by the United States Department of the Treasury, (b)&#160;&#8220;Book-Entry GSE Securities&#8221; as defined in the regulations of the United States Department of
      Housing and Urban Development governing direct obligations of FNMA and FHLMC (24&#160;C.F.R. Part&#160;81, as amended), or (c)&#160;&#8220;Book-Entry Funding Corporation Securities&#8221; as defined in the regulations of the United States Department of the Treasury governing
      securities issued by REFCO (12&#160;C.F.R. Part&#160;1511, as amended), and are, in each case, maintained in the Treasury/Reserve Automated Debt Entry System (&#8220;<b>Trades</b>&#8221;) of the Federal Reserve Bank pursuant to 31&#160;C.F.R. Subpart&#160;B.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Cash Deposit</b>&#8221; means a sum of cash no greater
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Certificates</b>&#8221; has the meaning set forth in the
      <b><u>Recitals</u></b>.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Claim</b>&#8221; has the meaning set forth in <b><u>Section
          22</u></b> herein.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Code</b>&#8221; means the Uniform Commercial Code of the
      State.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Custodian</b>&#8221; means the Intermediary in its
      capacity as custodian of the Pledged Collateral Account.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Defeasance</b>&#8221; has the meaning set forth in the <b><u>Recitals</u></b>.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Defeasance Assumption Agreement</b>&#8221; has the
      meaning set forth in the <b><u>Recitals</u></b>.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Defeasance Certificate</b>&#8221; means the Defeasance
      Certificate of even date herewith executed by Original Borrower.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Defeasance Documents</b>&#8221; means this Agreement, the
      Account Agreement, the Defeasance Assumption Agreement, the Waiver and Consent, the Defeasance Certificate, the Note, and all financing statements now or hereafter filed in connection with this Agreement and all other documents, instruments and
      agreements now or hereafter executed in connection with the Defeasance, all as amended, continued or otherwise modified; provided, that for purposes of any assumption of any obligations by the Successor Borrower under the Defeasance Assumption
      Agreement, the Waiver and Consent and the Defeasance Certificate shall be excluded from this definition.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Eligible Institution</b>&#8221; means (i)&#160;a federal or
      state chartered depository institution or trust company whose commercial paper, short-term debt obligations or other short-term deposits are rated at least &#8220;A-1&#8221; by S&amp;P, at least P1 by Moody&#8217;s and at least F-1+ by Fitch if the deposits in the
      Pledged Collateral Account are to be held for thirty (30) days or less, or (ii)&#160;a federal or state-chartered depository institution or trust company whose long-term unsecured debt obligations are rated at least &#8220;A+&#8221; by S&amp;P, at least &#8220;Aa3&#8221; by
      Moody&#8217;s and at least &#8220;AA-&#8221; by Fitch if the deposits in the Pledged Collateral Account are to be held for more than thirty (30) days, or (iii)&#160;the trust department of a federal or state chartered depository institution or trust company acting in its
      fiduciary capacity which institution or trust company is subject to regulations regarding fiduciary funds on deposit substantially similar to 12&#160;C.F.R. &#167;&#160;9.10(b), or (iv)&#160;an institution otherwise acceptable to each Rating Agency, as confirmed in
      writing that the holding by such institution of the Pledged Collateral Account would not, in and of itself, result in a downgrade, qualification or withdrawal of the then current ratings assigned to any of the Certificates.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Entitlement Order</b>&#8221; means &#8220;entitlement order&#8221; as
      defined in Section 8-102 of the Code.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Entity</b>&#8221; means a limited liability company.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Event of Default</b>&#8221; has the meaning set forth in
      <b><u>Section&#160;9(a)</u></b>.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Federal Book-Entry Regulations</b>&#8221; means the
      regulations of (a)&#160;the United States Department of the Treasury governing the transfer and pledge of marketable Book-Entry Securities maintained in the form of entries in the TRADES book-entry system in the Federal Reserve Bank, as set forth in
      31&#160;C.F.R. Part&#160;357, as amended, (b)&#160;the United States Department of Housing and Urban Development regulations governing the transfer and pledge of securities issued by FNMA or FHLMC, in each case maintained by a Federal Reserve Bank in the form of
      entries in the Book-Entry System (as defined in Subpart&#160;A of 24&#160;C.F.R. Part&#160;81) as set forth in Subpart&#160;H of 24&#160;C.F.R. Part&#160;81, and (c)&#160;the U.S. Treasury regulations governing the transfer and pledge of securities issued by REFCO, and maintained by a
      Federal Reserve Bank in the form of entries in the Book-Entry System (as defined in 12&#160;C.F.R. Part&#160;1511) as set forth in 12&#160;C.F.R. Part&#160;1511.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Federal Reserve Bank</b>&#8221; means the Federal Reserve
      Bank at which Intermediary maintains its Participant&#8217;s Securities Account.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>FHLMC</b>&#8221; means the Federal Home Loan Mortgage
      Corporation.</font></p>
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      Commencement Date.</font></p>
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      defined under Section 8-102(a)(9) of the Code.</font></p>
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      extent permitted by the Mortgage Loan Documents and acceptable to Lender and the Rating Agencies, other &#8220;government securities&#8221; as such term is defined in Section 2(a)(16) of the Investment Company Act of 1940, as amended (15 U.S.C. 80a-1, <i>et
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;2.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Pledge</u>.</b></font></td>
      </tr>

  </table>
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      Original Borrower hereby pledges, assigns, transfers and grants to Lender a continuing first priority security interest in and lien on all of the right, title and interest of Original Borrower in, to and under the following property (collectively,
      the &#8220;<b>Pledged Collateral</b>&#8221;):</font></p>
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      Borrower in the entries on the books of any Securities Intermediary (including Intermediary) pertaining to the Securities;</font></p>
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      Securities and with respect to any Permitted Investments (the &#8220;<b>Pledged Entitlements</b>&#8221;);</font></p>
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      Pledged Entitlements, including, without limitation, proceeds of any indemnity, warranty or guarantee payable from time to time with respect to any of the Securities or the Pledged Entitlements, or payments (in any form) made or due and payable to
      Pledgor from time to time in connection with any requisition, confiscation, condemnation, seizure or forfeiture of all or any part of the Securities or the Pledged Entitlements by or on behalf of any Governmental Authority, and any and all other
      amounts from time to time paid or payable under or in connection with any of the Securities or the Pledged Entitlements; and</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;any and all other (i)&#160;funds and Financial
      Assets and Proceeds thereof now or hereafter deposited in or credited to the Pledged Collateral Account at Intermediary (which account is the Securities Account), including the Cash Deposit, (ii)&#160;interest and earnings on any of the Pledged Collateral
      including interest that accrues either before or after the commencement of any bankruptcy or insolvency proceeding by or against Original Borrower or Successor Borrower, (iii)&#160;present and future accounts, general intangibles, chattel paper, contract
      rights, deposit accounts, instruments and documents (as defined in the Code or in the Uniform Commercial Code as in effect in any jurisdiction whose law applies to such property) now or hereafter relating or arising with respect to the Pledged
      Collateral Account and/or the use thereof, and (iv)&#160;cash and non-cash Proceeds and products of the items described in subclauses&#160;(i), (ii) and (iii) of this <b><u>Section 2(d)</u></b>.</font></p>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;3.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Secured Obligations</u>. </b></font></td>
      </tr>

  </table>
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      collateral security for, the payment and performance in full when due, whether at stated maturity, by acceleration or otherwise, of all of the Secured Obligations (including, without limitation, the payment of interest and other amounts which would
      accrue and become due but for the filing of a petition in bankruptcy (whether or not a claim is allowed against Original Borrower or Successor Borrower for such interest or other amounts in any such bankruptcy proceeding) or the operation of the
      automatic stay under the United States Bankruptcy Code, 11&#160;U.S.C. &#167;&#160;362(a)).</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;4.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>No Release or Assumption of Original Borrower&#8217;s Obligations to Others</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">The granting by Original Borrower to Lender of the
      security interest in the Pledged Collateral shall not relieve Original Borrower from the performance of any term, covenant, condition or agreement on Original Borrower&#8217;s part to be performed or observed on or prior to the date hereof in connection
      with the acquisition of the Pledged Collateral or from any liability to any Person other than Lender in connection with the acquisition of the Pledged Collateral and the granting of the security interest therein or impose any obligation on Lender to
      perform or observe any such term, covenant, condition or agreement to be so performed or observed by Original Borrower or impose any liability on Lender for any act or omission on the part of Original Borrower relating thereto or for any breach of
      any representation or warranty to any Person other than Lender by Original Borrower with respect to the acquisition of the Pledged Collateral or made in connection herewith or therewith. The provisions set forth in this <b><u>Section&#160;4</u> </b>shall
      survive any release of Original Borrower by Lender set forth in the Defeasance Documents and any termination of this Agreement.</font></p>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;5.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Further Assurances</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pledgor agrees that, upon written request of Lender at
      any time and from time to time, it will make, execute, endorse, acknowledge and file and refile, or permit Lender to file and refile, such lists, descriptions and designations of the Pledged Collateral, copies of documents of title, vouchers,
      invoices, schedules, Entitlement Orders, powers of attorney, assignments, confirmatory assignments, supplements, additional security agreements, financing statements, amendments thereto, continuation statements, transfer endorsements and other
      documents (including, without limitation, this Agreement), in form reasonably satisfactory to Lender wherever required or permitted by law in order to perfect, protect and preserve the rights and interests granted to Lender hereunder. Pledgor hereby
      authorizes Lender and appoints Lender as its attorney-in-fact to file such financing statements, continuation statements, amendments thereto and other documents related to the Pledged Collateral, without the signature of Pledgor, to the fullest
      extent permitted by applicable law, and Pledgor agrees to do such further acts and things, and to execute and deliver to Lender such additional assignments, agreements, powers and instruments, as Lender may reasonably require to effectuate the
      purposes of this Agreement, to preserve or protect the lien on the Pledged Collateral created by this Agreement, or to assure and confirm unto Lender its rights, powers and remedies hereunder. The foregoing grant of authority is a power of attorney
      coupled with an interest and such appointment shall be irrevocable for the term of this Agreement. All of the foregoing shall be at the sole cost and expense of Original Borrower on or prior to the date of this Agreement, and at the sole cost and
      expense of Successor Borrower after the date of this Agreement. The grant of rights and authority to Lender pursuant to the provisions set forth in this <b><u>Section&#160;5</u> </b>shall survive any release of Original Borrower by Lender set forth in
      the Defeasance Documents and any termination of this Agreement.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;6.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Original Borrower Representations, Warranties and Covenants</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      covenants as follows:</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.4in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Value</u>. Pledgor has received
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.4in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.4in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Rights in Pledged Collateral</u>.
      The Securities exist and Original Borrower is, as of the date hereof, and as to all Pledged Collateral acquired by it from time to time after the date hereof, Pledgor will be, the owner of good and marketable title to all of the Pledged Collateral,
      subject to only the liens granted to Lender pursuant to this Agreement and the assumption of the obligations of Original Borrower hereunder by Successor Borrower pursuant to the Defeasance Assumption Agreement.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.4in"><font style="font: 10pt Times New Roman, Times, Serif">(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Liens or Other Financing Statements</u>. Except
      for (1)&#160;the liens granted to Lender under this Agreement and financing statements filed or to be filed with respect to and covering the lien granted by Original Borrower pursuant to this Agreement, and (2)&#160;the assignment of the Pledged Collateral to
      Successor Borrower to be consummated immediately after the execution of this Agreement pursuant to the terms and conditions of the Defeasance Assumption Agreement, Original Borrower:</font></p>
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      existing, free and clear of any lien, claim, or encumbrance;</font></p>
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      granted a security interest in, or otherwise conveyed any of the Pledged Collateral, and shall defend the Pledged Collateral against all claims and demands of all Persons at any time claiming any interest therein adverse to Lender;</font></p>
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      knowledge of any control agreement or financing statement (or similar statement or instrument of registration under the law of any jurisdiction) covering or purporting to cover any interest of any kind in the Pledged Collateral, other than the
      Account Agreement; and so long as Original Borrower remains obligated to pay the Secured Obligations, Original Borrower shall not enter into any such control agreement or execute, file or authorize to be filed in any public office any financing
      statement (or similar statement or instrument of registration under the laws of any jurisdiction) or statements relating to the Pledged Collateral; and</font></p>
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      or tax liens against Original Borrower.</font></p>
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      Accountant&#8217;s Report and to the best of Original Borrower&#8217;s knowledge, all of the Securities are U.S. Obligations. Original Borrower has taken or caused, or authorized and directed other Persons to take, all actions necessary to effect the creation
      and perfection of Lender&#8217;s security interest in the Securities and other Pledged Collateral. This Agreement, together with the book entries described in <b><u>Section&#160;6(a)(viii)</u></b> below, and any other actions taken with respect to the Pledged
      Collateral pursuant to this Agreement, create a valid and continuing and perfected first priority security interest in the Pledged Collateral in favor of Lender pursuant to the Code, securing the Secured Obligations, and enforceable as such as
      against creditors of and purchasers from Original Borrower.</font></p>
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      Original Borrower is an Entity duly organized or incorporated, validly existing and in good standing under the laws of the Entity State and is duly qualified to conduct business in the state where the Mortgaged Property is located. Original Borrower
      has full power, authority and legal right to enter into this Agreement and to pledge and grant a lien on the Pledged Collateral pursuant to this Agreement. This Agreement has been duly authorized, executed and delivered by Original Borrower and
      constitutes the legal, valid and binding obligation of Original Borrower, enforceable against Original Borrower in accordance with its terms except as may be limited by bankruptcy, insolvency, reorganization, fraudulent conveyance, and similar laws
      affecting the rights of creditors generally.</font></p>
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      exception of the filing contemplated by <b><u>Section&#160;6(a)(iv)</u></b>, no authorization, consent, approval, license, qualification or formal exemption from, nor any filing, declaration or registration with, any court, Governmental Authority, or
      with any securities exchange or any other Person is required in connection with (1)&#160;the due execution, delivery or performance by Original Borrower of this Agreement, (2)&#160;the assignment of, and the grant of a lien on (including the priority thereof),
      the Pledged Collateral by Original Borrower in the manner and for the purpose contemplated by this Agreement, or (3)&#160;the exercise of the rights and remedies of Lender created hereby except those that have been obtained or made prior to or
      concurrently with the execution hereof, including, without limitation, filings in the appropriate offices under the Code.</font></p>
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      and delivery of this Agreement by Original Borrower, the consummation of the transactions herein contemplated by Original Borrower, and the compliance by Original Borrower with the terms and provisions hereof will not conflict with or result in a
      breach of, the formation documents of Original Borrower, any applicable law or regulation, or any order, writ, injunction or decree of any court or Governmental Authority, or any agreement or instrument to which Original Borrower is a party or by
      which Original Borrower is bound or to which any of the Pledged Collateral is subject, or result in the creation or imposition of any lien upon any earnings or assets of Original Borrower pursuant to the terms of any such agreement or instrument.</font></p>
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        Securities</u>. Original Borrower shall cause the Securities to be credited to Intermediary&#8217;s Participant&#8217;s Securities Account maintained at the Federal Reserve Bank at which Intermediary maintains a Participant&#8217;s Securities Account, and to be
      identified on the records of such Federal Reserve Bank as being held for the sole and exclusive account of Intermediary. Original Borrower does hereby (1)&#160;direct Intermediary to credit by book-entry such Securities to the Pledged Collateral Account
      of Lender and hold the same for the sole and exclusive account of Lender for the benefit of Lender, and (2)&#160;direct Intermediary to send a written confirmation to Lender that Intermediary has so credited the Securities to such Pledged Collateral
      Account and is holding the Securities for the sole and exclusive account of Lender for the benefit of Lender in accordance with the terms of this Agreement. Original Borrower hereby agrees that Intermediary is the Securities Intermediary at which the
      Pledged Collateral Account of Lender is maintained. Original Borrower hereby directs Intermediary to comply with all Entitlement Orders of Lender with respect to the Pledged Collateral.</font></p>
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      list of the Securities is complete and accurate and all of the Securities are Book-Entry Securities. If the Securities include securities identified as obligations of FHLMC or FNMA, they are direct debt obligations of such agency; if the Securities
      include securities identified as obligations of REFCO, they are interest-only strips that are direct obligations of REFCO. On the date hereof, all information set forth herein (including the exhibits hereto) and in the Accountant&#8217;s Report (including
      the schedules thereto), or otherwise provided to Lender by or on behalf of Original Borrower, is accurate and complete. None of the Securities is subject to prepayment call or early redemption, and all of the Securities are payable in United States
      Dollars.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      Original Borrower has complied, and shall continue to comply, with the single purpose entity requirements set forth in the Mortgage Loan Documents until the earlier of the date on which (1) Original Borrower has transferred all of its right, title
      and interest in the Pledged Collateral in accordance with the terms of the Defeasance Documents, or (2) all Secured Obligations have been paid in full and satisfied.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      value of the Mortgaged Property is greater than the fair market value of the Securities. Original Borrower has received reasonably equivalent value in exchange for the transfers contemplated by the Defeasance Documents.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(xii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Intent to Hinder Creditors</u>.
      The pledge of the Securities to Lender and the transfer of the Securities to Successor Borrower are not done in contemplation of insolvency or bankruptcy or with an intent to hinder, delay or defraud any of Original Borrower&#8217;s creditors.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(xiii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Insolvency</u>. Original
      Borrower is not insolvent immediately before signing this Agreement and is not being rendered insolvent by the pledge of the Securities to Lender or by the transfer of the Securities to Successor Borrower.</font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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      The assets owned by Original Borrower immediately after giving effect to the pledge of the Securities to Lender and the transfer of the Securities to Successor Borrower represent an amount of capital that is not unreasonably small for the business in
      which Original Borrower is engaged, and Original Borrower does not intend to engage in any other business for which such capital would be unreasonably small.</font></p>
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        Ability to Pay</u>. At the time of the pledge of the Securities to Lender and the transfer of the Securities to Successor Borrower, Original Borrower does not intend to, or believe that it will, incur debts that would be beyond its ability to pay
      as such debts mature.</font></p>
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      purpose in entering into the Defeasance is to facilitate a disposition of property or other customary commercial transaction and not as part of an arrangement to collateralize the REMIC pool evidenced by the Certificates with obligations that are not
      real estate mortgages.</font></p>
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      other proceeding is now pending or, to Original Borrower&#8217;s best knowledge, threatened against Original Borrower, wherein an unfavorable decision (1) would affect Original Borrower&#8217;s title to the Pledged Collateral, or (2) might reasonably be expected
      to result in a material adverse change in the financial condition of Original Borrower or its ability to legally perform its obligations under the Defeasance Documents.</font></p>
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      Original Borrower, nor the holder of any direct or indirect interest in Original Borrower, has incurred any indebtedness (including, but not limited to, any mezzanine debt, preferred equity debt, pari passu debt, senior secured debt, subordinate
      secured debt, or B-note debt) related to Original Borrower or the Mortgaged Property, other than the Mortgage Loan, indebtedness specifically authorized by the Mortgage Loan Documents, and any debt associated with the refinancing of the Mortgage Loan
      which is secured only by the Mortgaged Property. The Mortgage Loan Documents are not cross-collateralized or cross-defaulted with any other indebtedness and the Defeasance does not require notice to, or the consent of, the holder of any other
      indebtedness.</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(xix)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Transfers</u>. Except as
      specifically permitted by the Mortgage Loan Documents, Original Borrower has not sold, assigned, transferred, conveyed, pledged, granted a lien on or security interest in, encumbered, or otherwise disposed of (1) any direct interest in Original
      Borrower, (2) any indirect interest in Original Borrower, or (3) any direct or indirect interests in Original Borrower&#8217;s manager or managing member.</font></p>
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      obligations of Original Borrower hereunder, Successor Borrower shall be deemed to have made the following representations, warranties and covenants:</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Rights in Pledged
        Collateral</u>. The Securities exist and all information set forth in the Accountant&#8217;s Report and the schedules thereto is accurate and complete in all material respects. Successor Borrower is and, as to all Pledged Collateral acquired by Pledgor
      from time to time after the date hereof will be, the owner of good and marketable title to all of the Pledged Collateral, subject to only the liens granted to Lender pursuant to this Agreement. None of the Securities is subject to prepayment call or
      early redemption, and all of the Securities are payable in United States Dollars.</font></p>
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        Statements</u>. Except for the liens granted to Lender under this Agreement and financing statements filed or to be filed with respect to and covering the lien granted by Original Borrower pursuant to this Agreement, Successor Borrower:</font></p>
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      granted a security interest in, or otherwise conveyed any of the Pledged Collateral, and shall defend the Pledged Collateral against all claims and demands of all Persons at any time claiming any interest therein adverse to Lender; and</font></p>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;7.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Intermediary Representations, Warranties and Covenants</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;the Securities have been received by
      Intermediary and credited to the Participant&#8217;s Securities Account maintained by Intermediary at the Federal Reserve Bank free and clear of any liens, claims, interests or encumbrances (other than the lien created under the Defeasance Documents)
      created by, or claimed through, the Intermediary;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;the Pledged Entitlements have been and will
      continue to be credited, by accurate book entry, to and maintained in, the Pledged Collateral Account maintained by Intermediary for the benefit of Lender, and Lender is the holder of all Security Entitlements with respect to the Securities;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      Collateral Account at the current Intermediary Office Location, provided however, if Intermediary intends to move the Pledged Collateral Account to another location, it shall provide the Lender with not less than thirty (30) days prior written notice
      and the Intermediary shall cooperate with Lender in ensuring Lender&#8217;s continuing perfected security interest in the Pledged Collateral Account as required under the Code, including without limitation, the execution of any and all documents required
      to continue the Lender&#8217;s perfected security interest in the Pledged Collateral Account;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(h)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Lender has and shall continue to have
      &#8220;control&#8221; (as defined in Section&#160;8-106 of the Code) over the Securities, the Pledged Entitlements and the other Pledged Collateral;</font></p>
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      no actual knowledge of, any &#8220;adverse claim&#8221; (as defined in the Code) or lien or encumbrance as to the Pledged Collateral (including, but not limited to, any claim, lien or encumbrance in favor of the United States or any state) (other than the lien
      created under the Defeasance Documents);</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      limited to, any item of &#8220;investment property&#8221; (as defined under the Code), security instrument or cash, and every Security Entitlement in any of the foregoing) credited to the Pledged Collateral Account shall be treated by Intermediary as a Financial
      Asset subject to this Agreement;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(k)&#160;&#160;&#160;&#160;&#160;&#160;&#160;without limitation of any of the foregoing,
      it shall comply with all written Entitlement Orders originated by Lender without consent of Original Borrower or any other Person, and shall not accept Entitlement Orders from any Person other than Lender except as authorized in writing by Lender;
      and</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(l)&#160;&#160;&#160;&#160;&#160;&#160;&#160;it does not have, and will not take, a
      security interest in the Pledged Collateral or the Pledged Collateral Account, other than as custodian for the sole benefit of Lender, nor will it exercise any offset rights against the Pledged Collateral or the Pledged Collateral Account, and any
      security interest in the Pledged Collateral or the Pledged Collateral Account in favor of Intermediary that exists in violation of this provision shall be null and void.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;8.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Covenants Concerning the Pledged Collateral</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Intermediary and Pledgor hereby covenant, each as to
      itself, that:</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Waiver of Liens</u>. It waives and
      releases, solely for the benefit of Lender, any and all claim, lien, encumbrance or right of set off that it may now or hereafter have against the Pledged Collateral or any portion thereof.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Protection of Lender&#8217;s Security</u>. It
      shall not take any action that impairs the rights of Lender in the Pledged Collateral or the perfection of the security interests created hereunder.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Payments</u>. So long as no Event of
      Default shall have occurred and be continuing, all distributions, cash, interest, earnings, return of capital or other payments made in respect of the Pledged Collateral shall be deposited in the Pledged Collateral Account and utilized in accordance
      with the provisions of the Defeasance Documents (which utilization shall include, without limitation, the payment of scheduled installments due under the Note and the final payment on the Final Payment Date of the entire balance of the Mortgage
      Loan). At all times, whether before or during the continuation of any Event of Default, all rights to enforce and collect payments in respect of the Pledged Collateral or to direct the disposition thereof shall be exercised exclusively by Lender and
      the proceeds of any such exercise shall be applied to Pledgor&#8217;s obligations under the Defeasance Documents. In the event that any payments in respect of the Pledged Collateral are made directly to Pledgor, Pledgor shall hold such amounts as agent and
      trustee for Lender, segregate all amounts received pursuant thereto in a separate account and pay such amounts promptly to or as directed by Lender.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Transfers or Liens</u>. Except for the
      transfer of the Pledged Collateral by Original Borrower to Successor Borrower contemplated herein and in the Defeasance Assumption Agreement, it shall not (i)&#160;sell, convey, assign or otherwise dispose of, or grant any security interest, pledge,
      covenant, lien, option, right, warrant, or other encumbrance, whether junior or senior to the interest of Lender with respect to any of the Pledged Collateral, except to the extent Intermediary is permitted or required to transfer its rights and
      obligations to a successor pursuant to Sections&#160;4 and 7 of the Account Agreement, or (ii)&#160;create or, by its action or inaction, permit to exist any lien upon or with respect to any Pledged Collateral, except for the lien evidenced by this Agreement.</font></p>
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      <hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade"> </div>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;9.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Default; Remedies upon Default; Obtaining the Pledged Collateral upon Event of Default</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The occurrence and continuation of one or
      more of the following shall constitute an &#8220;<b>Event of Default</b>&#8221; hereunder:</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any default in the payment when due of
      any principal of or interest on the Mortgage Loan, including the payment of the entire balance of the Mortgage Loan due on the Final Payment Date, or default in the payment when due of any other amount payable with respect to the Secured Obligations,
      after the expiration of any applicable grace periods; or</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      certification made by any Person for the benefit of Lender in any Defeasance Document (or in any modification or supplement thereto), or in any certificate, report, financial statement or other item furnished to Lender in connection with this
      transaction shall prove to have been false or misleading in any material respect as of the time made or furnished and, if this shall be a result of conduct of a party other than Successor Borrower, such default results, or is likely, in Lender&#8217;s
      reasonable determination to result, in a default under <b><u>Section&#160;9(a)(i)</u></b>; or</font></p>
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      be rescinded (other than as a result of the termination of the Account Agreement by Lender and failure to appoint a substitute intermediary) or declared null and void, or shall fail to create or perfect the liens, rights, powers and privileges
      purported to be created thereby (including a perfected security interest in and lien on all of the Pledged Collateral, subject to no equal or prior lien) and, if this shall be a result of conduct of a party other than Original Borrower or Successor
      Borrower, such default results, or is likely, in Lender&#8217;s reasonable determination to result, in a default under <b><u>Section&#160;9(a)(i)</u></b>; or</font></p>
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      thereof or interest therein, or any direct or indirect interest in Successor Borrower becomes subject to any security interest, pledge, covenant, lien, or other encumbrance, whether junior or senior to the interest of Lender; or</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      thereof or interest therein, or any direct interest in Successor Borrower, or more than 49% of the indirect interests, in the aggregate, in Successor Borrower or in its manager, managing member or sole member, is sold, assigned, transferred,
      conveyed, or otherwise disposed of or is the subject of any attempted sale, assignment, transfer or conveyance without written consent of Lender and the Rating Agencies; or</font></p>
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vi)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any party to the Defeasance Documents
      other than Lender shall default in the performance of any of the other obligations to Lender under the Defeasance Documents and such default shall continue unremedied for a period of thirty (30) days after notice thereof and, if this shall be a
      result of conduct of a party other than Original Borrower or Successor Borrower, such default results, or is likely, in Lender&#8217;s reasonable determination to result, in a default under <b><u>Section&#160;9(a)(i)</u></b>; or</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Borrower (prior to the
      expiration of any preference period affecting the Pledged Collateral) or Successor Borrower shall admit in writing its inability to, or be generally unable to, pay its debts as such debts become due; or</font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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      conveyances with respect to Successor Borrower&#8217;s assets or assets held by Intermediary, any aspect of the transaction effected pursuant to the Defeasance Documents or any exercise by Lender of its rights or remedies thereunder, is challenged, voided,
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      is the debtor any claim shall be asserted that all or any portion of the Pledged Collateral is an asset of the debtor&#8217;s estate, or any aspect of the transaction effected pursuant to the Defeasance Documents, or any exercise by Lender of its rights or
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      Borrower) to the extent the same is permitted in such Defeasance Document; and</font></p>
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      Securities are sold on a recognized market and, accordingly, Lender need not furnish Pledgor with notice of its intention to sell the Securities. If, however, applicable law requires such notice, then upon the occurrence and during the continuance of
      an Event of Default, Lender may, upon ten (10) Business Days prior written notice to Pledgor of the time and place (except as provided to the contrary in the final sentence of this paragraph), sell, assign or otherwise dispose of all or any part of
      the Pledged Collateral or any part thereof that shall then be in, or shall thereafter come into, the possession, custody or control of Lender or any of its agents, at such place or places as Lender deems appropriate, and for cash or for credit or for
      future delivery, at public or private sale, without demand of performance or notice of intention to effect any such disposition or of the time or place thereof (except such notice as is required above or required by applicable statute, and cannot be
      waived), and Lender or anyone else may be the purchaser, assignee or recipient of any or all of the Pledged Collateral so disposed of at any public sale (or, to the extent permitted by law, at any private sale) and thereafter hold the same
      absolutely, free from any claim or right of any kind, including any right of equity of redemption (statutory or otherwise) of Pledgor, and Pledgor hereby expressly waives and releases any such demand of performance, notice (other than the notice set
      forth above and any non-waivable statutory notice) and right of equity of redemption. Lender may, without notice or publication, adjourn any public or private sale or cause the same to be adjourned from time to time by announcement at the time and
      place fixed for the sale, and such sale may be made at any time or place to which the sale may be so adjourned.</font></p>
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      disposition under this <b><u>Section&#160;9(d)</u></b> shall be applied in accordance with <b><u>Section&#160;9(c)</u></b> hereof.</font></p>
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      any claims against Lender arising by reason of the fact that the price at which the Pledged Collateral may have been sold at any such private sale was less than the price that might have been obtained at a public sale or was less than the aggregate
      amount of the Secured Obligations, even if Lender accepts the first offer received and does not offer the Pledged Collateral to more than one offeree.</font></p>
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        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;10.</b></font></td>
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      no course of dealing with respect to, and no delay on the part of Lender in exercising, any right, power or remedy hereunder shall operate as a waiver thereof. No single or partial exercise of any such right, power or remedy hereunder shall preclude
      any other or further exercise thereof or the exercise of any other right, power or remedy. The remedies herein provided are cumulative and are not exclusive of any remedies provided by law.</font></p>
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      each other party to any of the Defeasance Documents shall be restored to their respective former positions and rights hereunder with respect to the Pledged Collateral, and all rights, remedies and powers of Lender shall continue as if no such
      proceeding had been instituted.</font></p>
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      </tr>

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      has covenanted to do hereunder or if any warranty on the part of Pledgor contained herein shall be breached and such breach continues beyond any applicable grace or notice period, Lender or Servicer may (but shall not be obligated to), upon prior
      written notice to Pledgor specifying the action to be taken, do the same or cause it to be done or remedy any such breach, and may expend funds for such purpose. Any and all amounts so expended by Lender or Servicer (including, but not limited to,
      reasonable legal expenses and disbursements) shall be paid by Pledgor promptly upon demand therefor, with interest at the default rate specified in the Note, during the period from the date on which such payment is made to and including the date of
      repayment. Pledgor hereby authorizes Lender and Servicer and appoints Lender and Servicer as its attorneys-in-fact, with full authority in the place and stead of Pledgor and in the name of Pledgor, or otherwise, from time to time in Lender&#8217;s or
      Servicer&#8217;s reasonable discretion upon five (5) days prior written notice to Pledgor to take any action and to execute any instrument which is consistent and in accordance with the terms of this Agreement and the other Defeasance Documents and which
      Lender or Servicer may deem reasonably necessary or advisable to accomplish the purposes of this Agreement and the other Defeasance Documents. The foregoing grant of authority is a power of attorney coupled with an interest and such appointment shall
      be irrevocable for the term of this Agreement. Pledgor hereby ratifies all actions that such attorney shall lawfully take or cause to be taken in accordance with this <b><u>Section&#160;11</u></b>.</font></p>
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      </tr>

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      modified, amended, waived, extended, changed, discharged or terminated orally or by any act or failure to act on the part of Pledgor or Lender, but only by an agreement in writing and signed by all the parties hereto. Any amendment, modification or
      supplement of or to any provision of this Agreement, any waiver of any provision of this Agreement, and any consent to any departure by Pledgor from the terms of any provision of this Agreement shall be effective only in the specific instance and for
      the specific purpose for which made or given. Except where notice is specifically required by this Agreement, the other Defeasance Documents or applicable law, no notice to or demand on Pledgor in any case shall entitle Pledgor to any other or
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;13.</b></font></td>
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      </tr>

  </table>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;14.</b></font></td>
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  </table>
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      be received by the addressee on the third (3rd) Business Day following the day such notice is deposited with the United States postal service first class certified mail, postage prepaid, return receipt requested, or on the first (1st) day after
      deposit with such overnight courier, in either case addressed to the address set forth below for the party to whom such notice is to be given, or to such other address as Pledgor, Lender or Intermediary, as the case may be, shall in like manner
      designate by written notice given in accordance with this <b><u>Section 14</u></b>. Except where notice is specifically required by this Agreement, another of the Defeasance Documents, the Note, or applicable law, no notice or demand by Lender in
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  <table style="width: 100%; font: 11pt Times New Roman, Times, Serif; border-collapse: collapse" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
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        </td>
        <td>&#160;</td>
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      <tr style="vertical-align: top">
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        </td>
        <td>&#160;</td>
      </tr>

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      <hr style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000" noshade="noshade"> </div>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;15.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Continuing Security Interest; Assignment</u>. </b></font></td>
      </tr>

  </table>
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      interest in the Pledged Collateral and shall (a)&#160;be binding upon each party hereto and each of its successors and assigns, and (b)&#160;inure to the benefit of Lender and its successors and assigns. Without limiting the generality of the foregoing
      clause&#160;(b), Lender may assign or otherwise transfer any of the Secured Obligations to any other Person, and such other Person shall thereupon become vested with all the benefits in respect thereof granted to Lender, herein or otherwise. Except for
      the assignment to Successor Borrower contemplated by the terms and conditions of the Defeasance Assumption Agreement, Pledgor shall not, without the written consent of Lender and, if necessary, each rating agency that has issued a rating of the
      Certificates, assign its rights under this Agreement.</font></p>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;16.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Governing Law; Venue</u>. </b></font></td>
      </tr>

  </table>
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      INCLUDING SECTION 8-110(e) OF THE NEW YORK CODE AND SECTION&#160;357 OF THE FEDERAL BOOK-ENTRY REGULATIONS, THE STATE OF NEW YORK SHALL BE THE &#8220;<b>SECURITIES INTERMEDIARY&#8217;S JURISDICTION</b>&#8221;.</font></p>
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      EFFECT OF PERFECTION OR NON-PERFECTION AND PRIORITY OF THE RIGHTS AND INTERESTS OF LENDER IN THE PLEDGED COLLATERAL, AND ALL OTHER RIGHTS AND OBLIGATIONS OF THE PARTIES HEREUNDER SHALL IN ALL RESPECTS BE GOVERNED BY, AND CONSTRUED AND ENFORCED IN
      ACCORDANCE WITH, THE LAWS OF THE STATE, INCLUDING THE UNIFORM COMMERCIAL CODE AS ADOPTED IN THE STATE AND INCLUDING NEW YORK GENERAL OBLIGATIONS LAW SECTIONS&#160;5-1401 AND 5-1402 BUT OTHERWISE WITHOUT REGARD TO LAWS OF THE STATE CONCERNING CONFLICTS OF
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      AND VENUE OF ANY ACTION BROUGHT TO ENFORCE THIS AGREEMENT OR ANY OTHER DEFEASANCE DOCUMENT OR ANY ACTION RELATING TO THE TRANSACTIONS CONTEMPLATED HEREBY OR THE RELATIONSHIPS CREATED BY OR UNDER THE DEFEASANCE DOCUMENTS (&#8220;<b>ACTION</b>&#8221;) SHALL, AT
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      INTERMEDIARY HEREBY CONSENT AND SUBMIT TO THE PERSONAL JURISDICTION OF THE COURTS OF THE STATE AND OF FEDERAL COURTS LOCATED IN THE STATE IN CONNECTION WITH ANY ACTION AND HEREBY WAIVE ANY AND ALL PERSONAL RIGHTS UNDER THE LAWS OF ANY OTHER STATE TO
      OBJECT TO JURISDICTION WITHIN THE STATE FOR PURPOSES OF ANY ACTION. PLEDGOR, LENDER AND INTERMEDIARY HEREBY WAIVE AND AGREE NOT TO ASSERT, AS A DEFENSE TO ANY ACTION OR A MOTION TO TRANSFER VENUE OF ANY ACTION, (I)&#160;ANY CLAIM THAT IT IS NOT SUBJECT TO
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;17.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Severability of Provisions</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      determined by a court of law to be unenforceable in any jurisdiction shall, as to such jurisdiction, be ineffective to the extent of such prohibition or unenforceability without invalidating the remaining provisions hereof or affecting the validity
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;18.</b></font></td>
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      </tr>

  </table>
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      against a party when executed and delivered by an authorized individual on behalf of the party by means of (i) an original manual signature; (ii) a faxed, scanned, or photocopied manual signature, or (iii) any other electronic signature permitted by
      the federal Electronic Signatures in Global and National Commerce Act, state enactments of the Uniform Electronic Transactions Act, and/or any other relevant electronic signatures law, including any relevant provisions of the Code (collectively, &#8220;<b>Signature
        Law</b>&#8221;), in each case to the extent applicable. Each faxed, scanned, or photocopied manual signature, or other electronic signature, shall for all purposes have the same validity, legal effect, and admissibility in evidence as an original manual
      signature. Each party hereto shall be entitled to conclusively rely upon, and shall have no liability with respect to, any faxed, scanned, or photocopied manual signature, or other electronic signature, of any other party and shall have no duty to
      investigate, confirm or otherwise verify the validity or authenticity thereof. This Agreement may be executed in any number of counterparts, each of which shall be deemed to be an original, but such counterparts shall, together, constitute one and
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;19.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Headings</u>. </b></font></td>
      </tr>

  </table>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;20.</b></font></td>
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      </tr>

  </table>
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      referenced herein, constitutes the entire agreement and understanding of the parties hereto with respect to the matters and transactions contemplated hereby and supersedes all prior agreements and understandings whatsoever relating to such matters
      and transactions. This Agreement shall be binding upon and, subject to <b><u>Section&#160;15 </u></b>above, shall inure to the benefit of the successors and assigns of the parties hereto.</font></p>
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  <table style="width: 100%; margin-top: 0pt; margin-bottom: 0pt; font: 11pt Times New Roman, Times, Serif" border="0" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;21.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Limitation on Duty of Lender in Respect of Collateral</u>. </b></font></td>
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  </table>
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      pertaining thereto. Lender shall be deemed to have exercised reasonable care in the custody and preservation of the Pledged Collateral in its possession if the Pledged Collateral is accorded treatment substantially equal to that which Lender accords
      its own property, and shall not be liable or responsible for any loss or damage to any of the Pledged Collateral, or for any diminution in the value thereof, by reason of the act or omission of any agent or bailee selected by Lender in good faith.</font></p>
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      Borrower (but only as to Claims arising from acts or omissions of Original Borrower and to the extent that Indemnitee is the prevailing party)); provided that no Indemnitee shall have the right to be indemnified hereunder for its own negligence or
      willful misconduct as finally determined by a court of competent jurisdiction. The provisions of this <b><u>Section 22</u></b> shall survive the termination of this Agreement, the discharge of the obligations of Original Borrower, its successors and
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      because the Securities are insufficient to make scheduled payments of interest and principal as required under the Note, including payment of the Mortgage Loan in full on the Final Payment Date, without taking into account (a)&#160;reinvestment income, or
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  <p style="font: 11pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Any Person into which the Intermediary may be
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      business of the Intermediary shall be the successor of the Intermediary hereunder without the execution or filing of any paper or further act on the part of the Intermediary; provided, however, (i) such entity must be an Eligible Institution, and
      (ii) such entity must be deemed to have assumed all of the obligations of the Intermediary under the Defeasance Documents by operation of law or by written agreement. Nothing in this provision shall impair Lender&#8217;s termination rights under Section 7
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      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 27.</b></font></td>
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      </tr>

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      portion of any Mortgage Loan has priority or preference over any portion of any other Mortgage Loan. If for any reason the funds available in the Pledged Collateral Account are insufficient to satisfy all obligations then due under each of the Notes
      and the Defeasance Documents (including payments of each of the Mortgage Loans in full on the Final Payment Date), then any payment, whether principal or interest, under any of the Notes and any proceeds from the sale of the Pledged Collateral will
      be applied to the Mortgage Loans on a pro rata basis, based on the outstanding principal balance of each of the Mortgage Loans at the time such insufficiency occurs. Notwithstanding the foregoing, nothing in this <b><u>Section 27</u></b> modifies
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  <p style="margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>[Signatures on Following Pages]</b></font></p>
  <p style="margin-top: 0pt; margin-bottom: 0pt; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b> <br>
      </b></font></p>
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  <p style="margin: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">IN WITNESS WHEREOF, each of the parties hereto has caused this Agreement to be executed and
      delivered by its duly authorized officer as of the date first above written.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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        <td style="width: 50%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-variant: small-caps"><b>Original Borrower</b></font><b><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">:</font></b></td>
        <td style="width: 50%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>IONIS GAZELLE, LLC</b>,<br>
            a Delaware limited liability company</font></td>
      </tr>

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        <td style="width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">By:</font></td>
        <td style="width: 45%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Ionis Pharmaceuticals, Inc.,<br>
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        <td style="width: 5%"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">By:</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
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  <p style="margin-top: 0; margin-bottom: 0; text-align: right"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Signature page for Ionis Gazelle</font></p>
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        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">912828W48</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
        <td style="text-align: right; font-weight: bold; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">29-Feb-24</font></td>
      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">91282CEG2</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
        <td style="text-align: right; font-weight: bold; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">31-Mar-24</font></td>
      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">9128286R6</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
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      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">91282CFA4</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
        <td style="text-align: right; font-weight: bold; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">31-Jul-24</font></td>
      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">9128282U3</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
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      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">912828YH7</font></td>
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      </tr>
      <tr style="vertical-align: top; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">9128283P3</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
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      </tr>
      <tr style="vertical-align: top; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">9128284F4</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
        <td style="padding-left: 19pt; text-align: right; font-weight: bold; padding-right: 5pt"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">31-Mar-25</font></td>
      </tr>
      <tr style="vertical-align: bottom; background-color: white">
        <td style="padding-left: 8pt; text-align: left; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">T-NOTE</font></td>
        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">912828ZW3</font></td>
        <td style="padding-right: 14pt; text-align: right; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">20-Oct-22</font></td>
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      <tr style="vertical-align: bottom; background-color: white">
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        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">9128285C0</font></td>
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      <tr style="vertical-align: top; background-color: white">
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      <tr style="vertical-align: top; background-color: white">
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        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">91282CBH3</font></td>
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        <td style="padding-right: 0.5pt; padding-left: 0.5pt; text-align: center; font-weight: bold"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt; font-weight: normal; font-style: normal; background-color: white">91282CBQ3</font></td>
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  <p style="margin-top: 0; margin-bottom: 0; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      have the meanings set forth in the Pooling and Servicing Agreement.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Permitted Investments means any one or more of the
      following obligations or securities payable in United States Dollars on demand or on a scheduled maturity on or before the Business Day immediately preceding the date upon which the funds in the Pledged Collateral Account are required to be drawn,
      with maturities of not more than 365 days, regardless of whether issued by the Depositor, the Master Servicer, the Trustee or any of their respective affiliates, and having at all times the required ratings, if any, provided for in this definition,
      unless each Rating Agency shall have confirmed in writing to Servicer that a lower rating would not, in and of itself, result in a downgrade, qualification or withdrawal of the then current ratings assigned to the Certificates:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;obligations of, or obligations fully
      guaranteed as to payment of principal and interest by, the United States or any agency or instrumentality thereof provided such obligations are backed by the full faith and credit of the United States of America including, without limitation,
      obligations of: the U.S. Treasury (all direct or fully guaranteed obligations), the Farmers Home Administration (certificates of beneficial ownership), the General Services Administration (participation certificates), the U.S. Maritime Administration
      (guaranteed Title&#160;XI financing), the Small Business Administration (guaranteed participation certificates and guaranteed pool certificates), the U.S. Department of Housing and Urban Development (local authority bonds) and the Washington Metropolitan
      Area Transit Authority (guaranteed transit bonds); <u>provided</u>, <u>however</u>, that the investments described in this clause (1)&#160;must have a predetermined fixed dollar amount of principal due at maturity that cannot vary or change, (2)&#160;if such
      investments have a variable rate of interest, such interest rate must be tied to a single interest rate index plus a fixed spread (if any) and must move proportionately with that index, and (3)&#160;must not be subject to liquidation prior to their
      maturity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)&#160;&#160;&#160;&#160;&#160;&#160;Federal Housing Administration
      debentures;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)&#160;&#160;&#160;&#160;&#160;obligations of the following United
      States government sponsored agencies: Federal Home Loan Mortgage Corp. (debt obligations), the Farm Credit System (consolidated systemwide bonds and notes), the Federal Home Loan Banks (consolidated debt obligations), the Federal National Mortgage
      Association (debt obligations), the Financing Corp. (debt obligations), and the Resolution Funding Corp. (debt obligations); <u>provided</u>, <u>however</u>, that the investments described in this clause (1)&#160;must have a predetermined fixed dollar
      amount of principal due at maturity that cannot vary or change, (2)&#160;if such investments have a variable rate of interest, such interest rate must be tied to a single interest rate index plus a fixed spread (if any) and must move proportionately with
      that index, and (3)&#160;must not be subject to liquidation prior to their maturity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iv)&#160;&#160;&#160;&#160;&#160;federal funds, unsecured certificates of
      deposit, time deposits, bankers&#8217; acceptances and repurchase agreements with maturities of not more than 365 days, of any bank, the short term obligations of which are rated in the highest short term rating category by each Rating Agency (or otherwise
      acceptable to each Rating Agency, as confirmed in writing that such investment would not, in and of itself, result in a downgrade, qualification or withdrawal of the then current ratings assigned to the Certificates); <u>provided</u>, <u>however</u>,
      that the investments described in this clause (1)&#160;must have a predetermined fixed dollar amount of principal due at maturity that cannot vary or change, (2)&#160;if such investments have a variable rate of interest, such interest rate must be tied to a
      single interest rate index plus a fixed spread (if any) and must move proportionately with that index, and (3)&#160;must not be subject to liquidation prior to their maturity;&#160;</font></p>
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    <div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">C-1</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif"></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(v)&#160;&#160;&#160;&#160;&#160;&#160;Federal Deposit Insurance Corporation
      fully insured demand and time deposits in, or certificates of deposit of, or bankers&#8217; acceptances issued by, any bank or trust company, savings and loan association or savings bank, the short term obligations of which are rated in the highest short
      term rating category by each Rating Agency (or otherwise acceptable to each Rating Agency, as confirmed in writing that such investment would not, in and of itself, result in a downgrade, qualification or withdrawal of the then current ratings
      assigned to the Certificates); <u>provided</u>, <u>however</u>, that the investments described in this clause (1)&#160;must have a predetermined fixed dollar amount of principal due at maturity that cannot vary or change, (2)&#160;if such investments have a
      variable rate of interest, such interest rate must be tied to a single interest rate index plus a fixed spread (if any) and must move proportionately with that index, and (3)&#160;must not be subject to liquidation prior to their maturity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vi)&#160;&#160;&#160;&#160;&#160;debt obligations with maturities of not
      more than 365 days and rated by each Rating Agency in its highest long-term unsecured rating category (or otherwise acceptable to each Rating Agency, as confirmed in writing that such investment would not, in and of itself, result in a downgrade,
      qualification or withdrawal of the then current ratings assigned to the Certificates); <u>provided</u>, <u>however</u>, that the investments described in this clause (1)&#160;must have a predetermined fixed dollar amount of principal due at maturity
      that cannot vary or change, (2)&#160;if such investments have a variable rate of interest, such interest rate must be tied to a single interest rate index plus a fixed spread (if any) and must move proportionately with that index, and (3)&#160;must not be
      subject to liquidation prior to their maturity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vii)&#160;&#160;&#160;&#160;commercial paper (including both
      non-interest-bearing discount obligations and interest-bearing obligations payable on demand or on a specified date not more than one year after the date of issuance thereof) with maturities of not more than 365 days and that is rated by each Rating
      Agency in its highest short-term unsecured debt rating (or otherwise acceptable to each Rating Agency, as confirmed in writing that such investment would not, in and of itself, result in a downgrade, qualification or withdrawal of the then current
      ratings assigned to the Certificates); <u>provided</u>, <u>however</u>, that the investments described in this clause (1)&#160;must have a predetermined fixed dollar amount of principal due at maturity that cannot vary or change, (2)&#160;if such investments
      have a variable rate of interest, such interest rate must be tied to a single interest rate index plus a fixed spread (if any) and must move proportionately with that index, and (3)&#160;must not be subject to liquidation prior to their maturity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(viii)&#160;&#160;&#160;units of taxable money market mutual funds
      issued by regulated investment companies which seek to maintain a constant net asset value per share (including the Goldman FS Government MM Fund #465 (FGTXX) CUSIP #38141W273 (the &#8220;<b>Fund</b>&#8221;)) so long as such fund is rated by each Rating Agency
      that rates such fund in its highest long-term unsecured debt ratings category (or, if not rated by each Rating Agency, otherwise acceptable to each Rating Agency, as applicable, as confirmed in writing that such investment would not, in and of
      itself, result in a downgrade, qualification or withdrawal of the then current ratings assigned to the Certificates);</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ix)&#160;&#160;&#160;&#160;&#160;&#160;any other demand, money market or time
      deposit, demand obligation or any other obligation, security or investment, provided that each Rating Agency has confirmed in writing to the Master Servicer, Special Servicer or Trustee, as applicable, that such investment would not, in and of
      itself, result in a downgrade, qualification or withdrawal of the then current ratings assigned to the Certificates; and</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"></font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">C-2</font></div>
    <div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(x)&#160;&#160;&#160;&#160;&#160; such obligations as are included in the
      definition of &#8220;Permitted Investments&#8221; in the Pooling and Servicing Agreement or are otherwise acceptable as Permitted Investments to each Rating Agency, as confirmed in writing to Trustee, that such obligations would not, in and of itself, result in
      a downgrade, qualification or withdrawal of the then current ratings assigned to the Certificates;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><u>provided</u>, <u>however</u>, that, with respect to
      clause&#160;(ix) above, in the judgment of the Master Servicer, Special Servicer or Trustee, as applicable, such instrument qualifies as a &#8220;cash flow investment&#8221; pursuant to Section 860G(a)(6) of the United States Internal Revenue Code earning a passive
      return in the nature of interest and <u>provided</u> <u>further</u> that no instrument or security shall be a Permitted Investment if (a)&#160;such instrument or security evidences a right to receive only interest payments, (b)&#160;the right to receive
      principal and interest payments derived from the underlying investment provides a yield to maturity in excess of one hundred twenty percent (120%) of the yield to maturity at par of such underlying investment, or (c)&#160;such investments have a maturity
      in excess of one year.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center">&#160;<b><u>EXHIBIT D</u></b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>SINGLE PURPOSE ENTITY REQUIREMENTS</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Single Purpose Entity</b>&#8221; means (a) with respect
      to an existing Successor Borrower, the single purpose entity provisions in such entity&#8217;s formation documents, or (b) with respect to a new Successor Borrower formed pursuant to this Agreement, a business trust, corporation, limited partnership, or
      limited liability company (for purposes of this definition, the &#8220;<b>Entity</b>&#8221;) which, at all times since its formation and thereafter for so long as any of the Secured Obligations remain outstanding and not discharged in full:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;was and will be organized solely
      for the purpose of owning the Pledged Collateral and other similar collateral (collectively &#8220;<b>Pool Defeasance Collateral</b>&#8221;) owned by such Entity in connection with the defeasance of securitized loans from UBS Commercial Mortgage Trust 2017-C3,
      Commercial Mortgage Pass-Through Certificates, Series 2017-C3 securitization (the &#8220;<b>UBSCM 2017-C3 Pool</b>&#8221;) and performing and complying with the Defeasance Documents and other documents executed in connection with loans defeased from the UBSCM
      2017-C3 Pool (&#8220;<b>Pool Defeasance Documents</b>&#8221;), and has not and will not engage in any business unrelated to such purposes;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has not and will not have any
      assets other than the Pledged Collateral and Pool Defeasance Collateral;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has not and will not transfer,
      convey, grant, assign or pledge or permit the transfer, conveyance, granting, assignment or pledge of any of its assets or any interest therein except for the pledge of Pool Defeasance Collateral to Lender in connection with other Pool Defeasance
      Transactions;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iv)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has not and will not fail to
      correct any misunderstanding by a third party regarding the separate identity of such Entity when such Entity is aware of such misunderstanding;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(v)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has not permitted, cooperated with
      or sought involuntarily and will not permit, cooperate with or seek involuntarily the occurrence of any (1)&#160;bankruptcy, insolvency or reorganization petition or any relief under any laws relating to the relief from debts or the protection of debtors
      generally; (2)&#160;the appointment of a receiver, liquidator, assignee, trustee, sequestrator, custodian or any similar official; or (3)&#160;assignment for the benefit of creditors with respect to any beneficiary, partner or member of the Entity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vi)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has maintained and will maintain
      its accounts, books and records separate from any other person or entity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has maintained and will maintain
      its books, records, resolutions and agreements as official records;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(viii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has not commingled and will not
      commingle its funds or assets with those of any other person or entity;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ix)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has held and will hold its assets
      in its own name;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(x)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;has conducted and will conduct
      its business in its name;</font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">D-1</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>THIS DEFEASANCE ASSIGNMENT, ASSUMPTION AND RELEASE
        AGREEMENT</b> (this &#8220;<b>Agreement</b>&#8221;) dated as of October 20, 2022 is made by and among <font style="text-transform: uppercase"><b>IONIS GAZELLE, LLC</b></font>, a Delaware limited liability company (&#8220;<b>Original Borrower</b>&#8221;), <b>DHC UBSCM 17
        C3 SUCCESSOR BORROWER-R, LLC</b>, a Delaware limited liability company (&#8220;<b>Successor Borrower</b>&#8221;), <b>WELLS FARGO BANK, NATIONAL ASSOCIATION, AS TRUSTEE FOR THE BENEFIT OF THE REGISTERED HOLDERS OF UBS COMMERCIAL MORTGAGE TRUST 2017-C3,
        COMMERCIAL MORTGAGE PASS-THROUGH CERTIFICATES, SERIES 2017-C3</b>, as secured party (together with its successors and assigns, &#8220;<b>Lender</b>&#8221;), <b>MIDLAND LOAN SERVICES</b>, a division of PNC Bank, National Association (&#8220;<b>Servicer</b>&#8221;), on
      behalf of said Trustee under the Pooling and Servicing Agreement (as hereinafter defined), and, for the sole purpose of acknowledging the transactions effected by this Agreement, <b>U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION</b>, a national
      banking association, as Securities Intermediary and Custodian (together with its successors and assigns, &#8220;<b>Intermediary</b>&#8221;).</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>RECITALS<font style="font-variant: small-caps">:</font></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">A.&#160;&#160;&#160;&#160;&#160;&#160;&#160;UBS AG, by and through its branch office at
      1285 Avenue of the Americas, New York, New York (&#8220;<b>Original Lender</b>&#8221;), made a loan (the &#8220;<b>Mortgage Loan</b>&#8221;) to Original Borrower in the original principal amount of $51,350,000.00, made pursuant to a Loan Agreement dated July 18, 2017 (the &#8220;<b>Loan
        Agreement</b>&#8221;), and evidenced by (1) a Promissory Note A-1 dated July 18, 2017 in the original principal amount of $36,350,000.00 (the &#8220;<b>Note A-1</b>&#8221;), (2) a Promissory Note A-2 dated July 18, 2017 in the original principal amount of
      $5,000,000.00 (the &#8220;<b>Note A-2</b>&#8221;), and (3) a Promissory Note A-3 dated July 18, 2017 in the original principal amount of $10,000,000.00 (Note A-1, Note A-2 and Note A-3 are, individually and collectively, the &#8220;<b>Note</b>&#8221; or the &#8220;<b>Notes</b>&#8221;).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Mortgage Loan and the Notes are secured
      by, among other things, a Deed of Trust and Security Agreement dated July 18, 2017 from Original Borrower to and for the benefit of Original Lender (the &#8220;<b>Security Instrument</b>&#8221;), which grants to Original Lender, among other things, a lien on the
      real and personal property described in said Security Instrument (the &#8220;<b>Mortgaged Property</b>&#8221;). The Mortgage Loan is further evidenced or secured by various other documents, including guaranties, executed by Original Borrower and others in favor
      of Original Lender, including that certain Guaranty dated July 18, 2017, given by Ionis Pharmaceuticals, Inc., a Delaware corporation (&#8220;<b>Guarantor</b>&#8221;) (together with the Notes, the Loan Agreement and the Security Instrument, the &#8220;<b>Mortgage Loan
        Documents</b>&#8221;).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">C.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Lender assigned all of its right,
      title and interest in the Mortgage Loan and the Mortgage Loan Documents (by one or more assignments) to Lender in connection with the issuance of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3
      (the &#8220;<b>Certificates</b>&#8221;). Lender is the current holder of the Notes and the owner of the Mortgage Loan and the Mortgage Loan Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">D.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Servicer is the Master Servicer under the
      Pooling and Servicing Agreement dated as of August 1, 2017 (as from time to time amended, supplemented or modified, the &#8220;<b>Pooling and Servicing Agreement</b>&#8221;).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"></font></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">E.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Pursuant to the Mortgage Loan Documents,
      Original Borrower has directed Lender to release the Mortgaged Property and all escrows and reserves from the liens and security interests of the Security Instrument and the other Mortgage Loan Documents and to release any other collateral or
      security previously given by Original Borrower as security for the Mortgage Loan upon Original Borrower&#8217;s defeasance of the Mortgage Loan (the &#8220;<b>Defeasance</b>&#8221;).</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">F.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Borrower is the legal and beneficial
      owner of the securities listed in Exhibit A to the Pledge Agreement (collectively, the &#8220;<b>Securities</b>&#8221;). Pursuant to the Mortgage Loan Documents and as a condition precedent to Lender&#8217;s obligation to release the Mortgaged Property from the lien
      of the Security Instrument, Original Borrower has granted to Lender a security interest in the Securities and the proceeds thereof in accordance with the terms and conditions of the Defeasance Pledge and Security Agreement of even date herewith among
      Original Borrower, Lender, and Intermediary (the &#8220;<b>Pledge Agreement</b>&#8221;), to secure the payment and performance in full when due of all amounts payable under the Mortgage Loan Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">G.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;In connection with the Pledge Agreement,
      Original Borrower, Lender, Intermediary, Account Bank, and Servicer have entered into the Defeasance Account Agreement of even date herewith (the &#8220;<b>Account Agreement</b>&#8221;), pursuant to which Intermediary has established and will maintain an account
      to hold the interests of Original Borrower and Successor Borrower in the Securities and other collateral.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">H.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Pursuant to the Mortgage Loan Documents,
      Original Borrower is required or permitted to transfer and assign all of its obligations, rights and duties under and to the Note and the other Defeasance Documents (as defined in the Pledge Agreement), together with its right, title and interest in
      the Pledged Collateral (as defined in the Pledge Agreement), to a successor entity established or designated in accordance with the Mortgage Loan Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">I.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Successor Borrower has been established or
      designated as a single purpose successor entity which will assume certain of Original Borrower&#8217;s rights, obligations and liabilities under the Defeasance Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">J.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Borrower desires to (i) obtain the
      release of the Mortgaged Property and all escrows and reserves from the lien of the Security Instrument, (ii) transfer and assign certain of its rights and obligations under the Note and the other Defeasance Documents to Successor Borrower, (iii)
      transfer its right, title and interest in the Pledged Collateral to Successor Borrower, and (iv) obtain a release of its rights and obligations under the Mortgage Loan Documents, the Note, and the other Defeasance Documents to the extent provided
      herein. Successor Borrower, to the extent set forth in the Defeasance Documents, desires to assume Original Borrower&#8217;s rights and obligations under the Note, the Pledge Agreement and the Account Agreement and acquire Original Borrower&#8217;s right, title
      and interest in and to the Pledged Collateral.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">NOW, THEREFORE, in consideration of the mutual
      covenants and promises of the parties hereto and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties agree as follows:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; text-indent: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 1.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Definitions</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Each capitalized term used and not defined herein shall
      have the meaning assigned to such term in the Pledge Agreement or the Account Agreement, as applicable.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">2</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 2.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Assignment of Secured
          Obligations and Securities</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Effective as of the date hereof, Original Borrower
      hereby sells, transfers and assigns to Successor Borrower (a) all of Original Borrower&#8217;s obligations, rights (including the right, if any, to prepay the Mortgage Loan to the extent permitted by the Mortgage Loan Documents following the consummation
      of the Defeasance), liabilities and duties in, to and under, and subject to the terms of, the Note and the other Defeasance Documents (the &#8220;<b>Secured Obligations</b>&#8221;), and (b) all of Original Borrower&#8217;s right, title and interest in and to the
      Pledged Collateral, subject to the terms of the Defeasance Documents and to the rights of the Lender and the obligations of the Intermediary pursuant to the Pledge Agreement and the Account Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 3.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Assumption of Mortgage Loan
          Obligations</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Successor Borrower, for good and valuable
      consideration, the receipt and adequacy of which are hereby acknowledged, hereby assumes, and agrees to be bound by and to perform and/or be deemed to have made, as applicable, each of the Secured Obligations and all other covenants, agreements,
      representations and warranties of Original Borrower under the Note, the payment provisions of the Loan Agreement, the Pledge Agreement, and the Account Agreement first arising or accruing on or after the date of the transfer of the Pledged Collateral
      to Successor Borrower; <u>provided</u>, <u>however</u>, Successor Borrower shall not assume any obligations (i) under Section 4 of the Pledge Agreement (with respect to the Securities transferred to Successor Borrower on the date hereof), (ii)
      under Section 6 of the Pledge Agreement to the extent that such obligations are to have been fully performed by Original Borrower or parties other than Successor Borrower prior to transfer of the Securities to Successor Borrower, (iii) that arise as
      a result of Original Borrower&#8217;s failure to effect the initial perfection of Lender&#8217;s interest in the Pledged Collateral prior to the transfer of the Pledged Collateral to Successor Borrower, (iv) that may arise as a result of any material
      misrepresentation or misstatement made by Original Borrower in any of the Defeasance Documents or otherwise made by Original Borrower in connection with the defeasance transaction contemplated under this Agreement, which representation or statement
      Original Borrower knew or should have known when made to be a material misrepresentation or misstatement, or (v) that arise under the Note or the Mortgage Loan Documents (to the extent that provisions of the Mortgage Loan Documents have been
      incorporated into the Note), that (1) specifically relate to the use or operation of the Mortgaged Property, including without limitation, any real property-related events of default set forth in the Note, (2) do not otherwise relate to payment terms
      under the Note, or (3) directly conflict with any express covenant made or assumed by Successor Borrower under the Defeasance Documents, or (vi) for any costs, payments and expenses other than those expressly assumed herein.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;Except as otherwise expressly provided
      herein, Successor Borrower shall be liable to Lender only to the extent of the Pledged Collateral and other Pool Defeasance Collateral that has been pledged to Lender in connection with Pool Defeasance Transactions except that Successor Borrower
      shall be required to advance funds to cover any shortfall if at any time the funds available in the Pledged Collateral Account are insufficient to pay amounts then due with respect to the Secured Obligations without taking into account (1)
      reinvestment income, or (2) failure by any Obligor to satisfy its obligations under the Securities. Lender shall have no recourse against, and Lender shall not enforce any monetary judgment with respect to the Secured Obligations against assets of
      Successor Borrower other than the Pledged Collateral and other Pool Defeasance Collateral; <u>provided</u>, <u>however</u>, Lender shall not enforce any monetary judgment against other Pool Defeasance Collateral until the defeased promissory note
      related to such Pool Defeasance Collateral has been repaid in full in accordance with its terms.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"></p>
  <div id="DSPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div id="DSPFPageNumberArea" style="TEXT-ALIGN: center"><font id="DSPFPageNumber" style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">3</font></div>
    <div id="DSPFPageBreak" style="PAGE-BREAK-AFTER: always">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notwithstanding the provisions of <b><u>Section
          3(b)</u></b> above, Successor Borrower (but not its directors, members, or managers) shall be personally liable for all claims, demands, liabilities, deficiencies, losses, damages, judgments, costs, and expenses, including without limitation
      reasonable attorneys&#8217; fees and costs of collection incurred, suffered or paid by Lender as a result of:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;any representation, warranty or
      certification made by or on behalf of Successor Borrower for the benefit of Lender in any Defeasance Document (or in any modification or supplement thereto), or in any certificate, report, financial statement or other item furnished to Lender in
      connection with this transaction having been false or misleading in any material respect as of the time made or furnished;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      thereof or interest therein becoming subject to any security interest, pledge, covenant, lien, or other encumbrance, whether junior or senior to the interest of Lender, as a result of actions of Successor Borrower;</font></p>
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      thereof or interest therein being sold, assigned, transferred, conveyed or otherwise disposed of, or becoming the subject of any attempted sale, assignment, transfer or conveyance, by Successor Borrower;</font></p>
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      subsections (iv) through (xii) of Section 9(a) of the Pledge Agreement shall occur as a result of actions of Successor Borrower or circumstances relating to Successor Borrower;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      to be a Single Purpose Entity; or</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      immediately deposit into the Pledged Collateral Account an amount sufficient to pay any shortfall if, at any time, funds available in the Pledged Collateral Account are insufficient to satisfy all obligations then due under the Note or under any
      other Defeasance Document arising because the Securities are insufficient to make scheduled payments of interest and principal as required under the Note, including payment of the Mortgage Loan in full on the Final Payment Date without taking into
      account (1) reinvestment income, or (2) failure by any Obligor to satisfy its obligations under the Securities.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Successor Borrower&#8217;s assumption of the
      obligations of Original Borrower as set forth above under the Defeasance Documents is limited to those obligations arising on and after the date hereof, except that Successor Borrower expressly assumes (i) liability under the Note for interest
      accruing on the Mortgage Loan from and after the first day of the interest accrual period in which the Defeasance contemplated herein occurs (or in the event the next Scheduled Monthly Payment is being made in connection with the Defeasance closing,
      then Successor Borrower shall be liable for interest accruing on the Mortgage Loan from and after the due date of such Scheduled Monthly Payment), which shall be deposited by Original Borrower in the Pledged Collateral Account on or before the date
      hereof and paid in accordance with the provisions of the Account Agreement from the Pledged Collateral Account, and (ii) any liability that may arise if the Securities are insufficient to make timely payments in accordance with the Account Agreement
      (other than any insufficiency resulting from the failure of Obligor to make timely payments with respect to the Securities). Notwithstanding the foregoing, Successor Borrower hereby ratifies and confirms the representations, warranties and covenants
      in the Pledge Agreement made solely as to Successor Borrower.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      Defeasance Documents, Successor Borrower hereby grants to Lender and Servicer a power of attorney to file any franchise or other administrative filings which may be required to maintain Successor Borrower&#8217;s good standing and legal existence in the
      event Successor Borrower fails to do so within ten (10) days following receipt of written notice from Lender of such failure. Any and all losses, expenses and costs of any nature or kind whatsoever which may be paid or incurred by Lender or Servicer
      as a result of Successor Borrower&#8217;s failure to maintain its good standing and legal existence are specifically included within the Secured Obligations for which the Securities and any proceeds thereof are pledged.</font></p>
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      Lender may have under the Defeasance Documents or Mortgage Loan Documents to the extent assumed by Successor Borrower, in the event of the failure of Successor Borrower to maintain its status as a Single Purpose Entity in good standing, Successor
      Borrower&#8217;s failure to file all required tax returns and pay all taxes which it owes or Successor Borrower&#8217;s failure to file all forms and documents required to maintain its separate legal existence, in each case which failure continues for ten (10)
      days (the &#8220;<b>Cure Period</b>&#8221;) after Successor Borrower&#8217;s receipt of written notice thereof, Successor Borrower hereby agrees to the assumption of the Mortgage Loan by, and the transfer of the Pledged Collateral to, a Single Purpose Entity
      designated by Lender and hereby appoints Lender and Servicer as attorneys in fact with power of attorney to effect such transfer and assumption, provided that Lender agrees that the exercise of its rights hereunder to designate a successor Single
      Purpose Entity shall not be exercised for non-material technical defaults of the single purpose entity requirements, and further provided that Lender shall have the right to exercise its remedies hereunder without compliance with the Cure Period if
      Lender determines in its reasonable discretion that the Cure Period could materially diminish the value of, or otherwise materially affect, the Pledged Collateral or the Lender&#8217;s security interest therein.</font></p>
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      Successor Borrower hereby pledges, assigns, transfers and grants to Lender a continuing first priority security interest in and lien on all of the right, title and interest of Successor Borrower (as assigned from Original Borrower) in, to and under
      the Pledged Collateral whether now owned or existing or hereafter acquired or arising. Successor Borrower hereby authorizes the filing of UCC financing statements describing the Pledged Collateral. Original Borrower hereby ratifies and affirms the
      security interest that it has granted in the Pledged Collateral pursuant to the Pledge Agreement.</font></p>
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          of Lender</u>. </b></font></p>
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      conditions to the Defeasance set forth in the Mortgage Loan Documents, and (b) the Defeasance Documents, Lender hereby recognizes and consents to Original Borrower&#8217;s transfer and assignment to Successor Borrower of Original Borrower&#8217;s rights in the
      Pledged Collateral and its rights and obligations under the Defeasance Documents in accordance with <b><u>Section 2</u></b> above, and the assumption by Successor Borrower of Original Borrower&#8217;s rights in the Pledged Collateral and its rights and
      obligations under the Defeasance Documents in accordance with <b><u>Section 3</u></b> above.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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          Borrower and Guarantor</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      all conditions to the Defeasance set forth in the Mortgage Loan Documents, Lender (i) shall promptly release and discharge the Mortgaged Property and all escrows and reserves from the lien of the Security Instrument and the other Mortgage Loan
      Documents, (ii) authorizes Original Borrower to terminate any UCC financing statements filed in connection with the Mortgage Loan naming Original Borrower as debtor, and listing all or any portion of the Mortgaged Property as collateral therein, and
      (iii) hereby releases and discharges Original Borrower and Guarantor from all claims, liabilities and obligations under the Mortgage Loan Documents, the Note, and the other Defeasance Documents related to events first occurring or arising after the
      transfer of the Pledged Collateral to Successor Borrower; <u>provided</u>, <u>however</u>, Original Borrower and Guarantor shall not be released from liability for any loss or damages suffered, or expenses incurred, by Lender, Intermediary or
      Successor Borrower as a result of or established pursuant to a claim, liability or obligation:</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;arising from Original Borrower&#8217;s
      obligations under Sections 4, 5, 6 or 22 of the Pledge Agreement that have not been expressly assumed by Successor Borrower under this Agreement;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      warranty or certification of Original Borrower or Guarantor under the Defeasance Documents or the Mortgage Loan Documents or in any certificate, report, financial statement or other item delivered by Original Borrower or Guarantor in connection
      therewith that proves to have been false or misleading in any material respect when made or delivered;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;arising as a result of the transfer of,
      or creation and perfection of, the first priority lien on the Pledged Collateral being deemed void or voidable for any reason whatsoever, or any other payment made by Original Borrower in respect of amounts due under the Mortgage Loan Documents on or
      prior to the date hereof being recovered from the Lender by Original Borrower, its creditors, or any other person for any reason whatsoever claiming by or through Original Borrower;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iv)&#160;&#160;&#160;&#160;&#160;&#160;&#160;for any other failure by Original
      Borrower to pledge the Pledged Collateral to Lender or take or authorize any action necessary to effect the first priority perfection of Lender&#8217;s security interest therein on or before the date hereof or to effectively transfer the Pledged Collateral
      to Successor Borrower in accordance with the Defeasance Documents;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(v)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;arising under any environmental or
      hazardous materials indemnity agreement or any other indemnity obligation or other obligation set forth in the Mortgage Loan Documents that, by its terms, is intended to survive the release of the lien of the Security Instrument to the extent the
      event giving rise to such liability occurred prior to the date hereof; or</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vi)&#160;&#160;&#160;&#160;&#160;&#160;&#160;arising as a result of an Event of
      Default under the Pledge Agreement that results from circumstances relating to Original Borrower, or actions of Original Borrower, included in subsections (iii) through (viii) and (xii) and (xiii) of Section 9(a) of the Pledge Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Without limiting any other remedies Lender
      may have, upon the occurrence of any Event of Default arising under the Mortgage Loan Documents from any breach, act or omission of Original Borrower or Guarantor prior to the date hereof, Lender shall be entitled to enforce all of its remedies set
      forth in the Mortgage Loan Documents against Original Borrower or Guarantor. Except as expressly set forth in this <b><u>Section 5</u></b>, Lender hereby releases Original Borrower and Guarantor from their respective obligations under the Mortgage
      Loan Documents and the Defeasance Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 6.&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Release of Lender and
          Servicer</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Original Borrower and Guarantor hereby covenant and
      agree that: (a) from and after the date hereof, Lender and Servicer may deal solely with Successor Borrower in all matters relating to the Mortgage Loan; (b) Lender and Servicer have no further duty or obligation of any nature relating to the
      Mortgage Loan or the Mortgage Loan Documents to Original Borrower and Guarantor (except that the Servicer agrees to return to Original Borrower promptly following the date hereof any escrows or reserves, minus any outstanding fees due, that it holds
      pursuant to the Mortgage Loan Documents); and (c) Original Borrower and Guarantor hereby release Lender and Servicer, and each of their predecessors-in-interest, together with all officers, directors, employees and agents of each of the foregoing,
      from all claims, causes of action and liabilities relating directly or indirectly to the Mortgage Loan, the Mortgaged Property, the Mortgage Loan Documents and the closing of the Defeasance arising on or prior to the date hereof, including any and
      all claims arising from or relating to negotiations, demands, requests or exercise of remedies in connection with the Mortgage Loan and the closing of the Defeasance.</font></p>
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          Warranties</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      to the other parties hereto that, as of the date hereof:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;all principal, interest and other amounts
      due and payable on or before the date hereof under the Note and the other Mortgage Loan Documents have been paid;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      continuing under any of the Mortgage Loan Documents beyond any applicable grace or notice period;</font></p>
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      contain provisions requiring Original Borrower to make any scheduled payments that by their terms would be payable on or after the date of the closing of the Defeasance contemplated herein, other than scheduled payments of principal and interest
      under the Note, including annual surveillance fees of rating agencies or servicing or trustees fees with respect to securitization of the Mortgage Loan, except such payments as have been specifically identified by Original Borrower and either (1)
      expressly assumed by Successor Borrower under the Defeasance Documents, or (2) paid in full in advance by Original Borrower in connection with the closing of the Defeasance contemplated herein.</font></p>
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      to the other parties hereto, and hereby covenants for the benefit of such parties, that:</font></p>
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      liability company, duly organized, validly existing and in good standing under the laws of the State of Delaware. Successor Borrower has all requisite power and authority to carry on its business as now conducted and as proposed to be conducted, and
      to enter into and perform its obligations under this Agreement and the other Defeasance Documents;</font></p>
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      Agreement, the assumption of the Original Borrower&#8217;s rights and obligations under the Pledge Agreement, the Account Agreement and the Note, and performance of all of Successor Borrower&#8217;s rights and obligations thereunder have been duly authorized by
      all necessary and appropriate action of Successor Borrower;</font></p>
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      entity, or governmental authority is required with respect to the execution and delivery of this Agreement by Successor Borrower or the consummation by Successor Borrower of the transactions contemplated hereby or the performance by Successor
      Borrower of its obligations under this Agreement and the other Defeasance Documents, except such consents or approvals as have already been obtained;</font></p>
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      the Account Agreement (as assumed pursuant to this Agreement) are the legal, valid and binding obligations of the Successor Borrower, enforceable against the Successor Borrower in accordance with their respective terms, except as may be limited by
      bankruptcy, insolvency, reorganization, moratorium, fraudulent conveyance or other similar laws of general applicability affecting the enforcement of creditors&#8217; rights;</font></p>
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      Borrower is Delaware. The taxpayer identification number of the Successor Borrower is 83-2813361. Successor Borrower&#8217;s organizational identification number is 6490626;</font></p>
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      has not changed its jurisdiction of organization. Successor Borrower shall not change its name as it appears in the organizational documents on file in its jurisdiction of organization, or change its jurisdiction of organization until (1) it has
      given Lender not less than thirty (30) days prior written notice of its intention to do so, clearly describing the new name or jurisdiction, and (2) it has provided Lender with any information regarding the new name or jurisdiction as Lender may
      request. If Successor Borrower intends to change its name or change its jurisdiction of organization, Successor Borrower shall cooperate with Lender in taking all action required by Lender to maintain perfection, priority and validity of the lien of
      Lender in the Pledged Collateral granted by the Pledge Agreement;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      knowledge of any adverse claim, lien or encumbrance with respect to the Pledged Collateral;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      of UCC-1 financing statements is as set forth in <b><u>Section 17</u></b>;&#160;</font></p>
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      formation, and shall at all times continue to be, a Single Purpose Entity in good standing in the jurisdiction in which it has been organized. Successor Borrower shall deliver to Lender, within thirty (30) days after written request from Lender, a
      certification signed by an officer of Successor Borrower or of Successor Borrower&#8217;s managing member or general partner, as applicable, certifying that such officer is familiar with the activities and operations of Successor Borrower and all
      transactions entered into by Successor Borrower during the preceding twelve months (or since the date of Successor Borrower&#8217;s formation if Successor Borrower was formed during such preceding twelve month period) and that, to such officer&#8217;s knowledge,
      Successor Borrower has conducted itself as a Single Purpose Entity during such period, has filed all tax returns required to be filed during such period and has paid all taxes due and payable (and not being contested in accordance with the Defeasance
      Documents or applicable law) during such period. If requested by Lender, each such certification shall be accompanied by an original certificate of existence or good standing issued by the Secretary of State of the jurisdiction of Successor
      Borrower&#8217;s formation, dated not more than thirty (30) days prior to the date of such certification;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">(x)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the proceeds of the Securities (without regard to
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      deposit into the Pledged Collateral Account an amount sufficient to pay any shortfall if, at any time, funds available in the Pledged Collateral Account are insufficient to satisfy all obligations then due under the Note or under any other Defeasance
      Document arising because the Securities are insufficient to make scheduled payments of interest and principal as required under the Note, including payment of the Mortgage Loan in full on the Final Payment Date, without taking into account (1)
      reinvestment income, or (2) failure by any Obligor to satisfy its obligations under the Securities;</font></p>
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      not permit any Person to, sell, assign, transfer, convey, pledge or otherwise dispose of all or any interest in Successor Borrower, or the Pledged Collateral in violation of Subsection (iv) and (v) of Section 9(a) of the Pledge Agreement;</font></p>
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      filed with the Secretary of State of the jurisdiction of organization of Successor Borrower, a UCC financing statement (naming Successor Borrower, as debtor) evidencing the liens and security interests or pledge created by this Agreement. Successor
      Borrower acknowledges that this Agreement, together with the book entries described in Section 6(a)(viii) of the Pledge Agreement, the filing of the UCC financing statement contemplated above, and any other actions taken with respect to the Pledged
      Collateral pursuant to this Agreement, create a valid and continuing and perfected first priority security interest in the Pledged Collateral in favor of Lender pursuant to the Code, securing the Secured Obligations, and enforceable as such as
      against creditors of and purchasers from Successor Borrower;</font></p>
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      Intermediary is the Securities Intermediary at which the Pledged Collateral Account of Lender is maintained. Successor Borrower hereby directs Intermediary to comply with all Entitlement Orders of Lender issued in connection with the terms of this
      Agreement with respect to the Pledged Collateral;</font></p>
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      has no knowledge of any control agreement or financing statement (or similar statement or instrument of registration under the law of any jurisdiction) covering or purporting to cover any interest of any kind in the Pledged Collateral and, except as
      may be required by Lender or Servicer, shall not enter into any such control agreement or execute, file or authorize to be filed in any public office any financing statement (or similar statement or instrument of registration under the laws of any
      jurisdiction) or statements relating to the Pledged Collateral;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(xvi)&#160;&#160;&#160;&#160;&#160;Successor Borrower shall deliver to
      Servicer and Intermediary (1) an executed Internal Revenue Service Form W-9 or an appropriate IRS form W-8, as applicable, no later than the Closing Date, and (2) upon request, any additional IRS forms (or updated versions of any previously submitted
      IRS forms) or other documentation at such time or times required by applicable law or upon the reasonable request of the Intermediary (as withholding agent) as may be necessary (A) to reduce or eliminate the imposition of U.S. withholding taxes and
      (B) to permit Intermediary to fulfill its tax reporting obligations under applicable law with respect to the Pledged Collateral Account or any amounts paid to Successor Borrower. If any IRS form or other documentation previously delivered becomes
      obsolete or inaccurate in any respect, upon request, Successor Borrower shall timely provide to the Intermediary accurately updated and complete versions of such IRS forms or other documentation; <u>provided</u>, <u>however</u>, that if the
      Successor Borrower&#8217;s entity or form of entity has changed, then the Successor Borrower shall promptly provide such updated form to the Intermediary;&#160;</font></p>
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      writing in the event Successor Borrower, together with any affiliate of Successor Borrower that is the successor borrower under one or more defeased loans held by Lender, is the current obligor under loans which, in the aggregate, equal or exceed
      $35,000,000.00 or 5% of the aggregate principal balance of all loans in any pool of loans governed by a Pooling and Servicing Agreement rated by S&amp;P (as defined in the Account Agreement); and</font></p>
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      and its subsidiaries, including Successor Borrower, (2) has a net worth of at least $35,000,000.00, and (3) has cash and cash equivalents in excess of $3,500,000.00.</font></p>
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      any fees charged by the Intermediary related to investments in Default Permitted Investments or to wire transfers to the Collection Account from the Pledged Collateral Account or to Successor Borrower are included in fees that have already been paid
      to Intermediary.</font></p>
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      Consent, Original Borrower represents, warrants and covenants that it has satisfied the conditions set forth in the defeasance provisions of the Mortgage Loan Documents required to effectuate the release of the Mortgaged Property from the lien of the
      Security Instrument and the closing of the Defeasance of the Mortgage Loan on the date hereof, or such conditions have been waived in writing by Lender. Original Borrower will deliver the Defeasance Certificate to Lender on the date hereof, and
      Original Borrower acknowledges that Successor Borrower will rely on such Defeasance Certificate and on the representations set forth herein as a condition to entering into this Agreement. Original Borrower further acknowledges and agrees that all
      proceeds from the Pledged Collateral in excess of amounts due under the Defeasance Documents will be the sole property of Successor Borrower.</font></p>
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      otherwise changed in any manner, except by a writing executed by all of the parties to this Agreement. Notwithstanding the foregoing, from and after the date hereof, any new agreement pertaining to the Mortgage Loan and any amendment, modification or
      extension of the Note or the Defeasance Documents may be made solely by Successor Borrower and Lender and shall not require the consent or execution of Original Borrower. No such changes will increase Original Borrower&#8217;s obligations or liabilities
      under the Mortgage Loan Documents and the Defeasance Documents that continue after the date of this Agreement as set forth in <b><u>Section 5</u></b> above.</font></p>
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      Borrower hereby represents and warrants to Lender that such entity has obtained any and all third-party approvals and consents required to be obtained in connection with the execution and delivery of this Agreement and the performance of such
      entity&#8217;s obligations hereunder.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">THIS AGREEMENT AND ALL RIGHTS AND OBLIGATIONS OF THE
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">ORIGINAL BORROWER, LENDER, SUCCESSOR BORROWER, SERVICER
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      RELATING TO THIS AGREEMENT. JURISDICTION AND VENUE OF ANY ACTION BROUGHT TO ENFORCE THIS AGREEMENT OR ANY OTHER DEFEASANCE DOCUMENT OR ANY ACTION RELATING TO THE TRANSACTIONS CONTEMPLATED HEREBY OR THE RELATIONSHIPS CREATED BY OR UNDER THE DEFEASANCE
      DOCUMENTS (&#8220;<b>ACTION</b>&#8221;) SHALL, AT THE ELECTION OF LENDER, BE IN (AND IF ANY ACTION IS ORIGINALLY BROUGHT IN ANOTHER VENUE, THE ACTION SHALL AT THE ELECTION OF LENDER BE TRANSFERRED TO) A STATE OR FEDERAL COURT OF APPROPRIATE JURISDICTION LOCATED
      IN THE STATE. ORIGINAL BORROWER, LENDER, SUCCESSOR BORROWER, SERVICER AND INTERMEDIARY HEREBY CONSENT AND SUBMIT TO THE PERSONAL JURISDICTION OF THE COURTS OF THE STATE AND OF FEDERAL COURTS LOCATED IN THE STATE IN CONNECTION WITH ANY ACTION AND
      HEREBY WAIVE ANY AND ALL PERSONAL RIGHTS UNDER THE LAWS OF ANY OTHER STATE TO OBJECT TO JURISDICTION WITHIN THE STATE FOR PURPOSES OF ANY ACTION. ORIGINAL BORROWER, LENDER, SUCCESSOR BORROWER, SERVICER AND INTERMEDIARY HEREBY WAIVE AND AGREE NOT TO
      ASSERT, AS A DEFENSE TO ANY ACTION OR A MOTION TO TRANSFER VENUE OF ANY ACTION, (I) ANY CLAIM THAT IT IS NOT SUBJECT TO SUCH JURISDICTION; (II) ANY CLAIM THAT ANY ACTION MAY NOT BE BROUGHT AGAINST IT OR IS NOT MAINTAINABLE IN THOSE COURTS OR THAT
      THIS AGREEMENT MAY NOT BE ENFORCED IN OR BY THOSE COURTS, OR THAT IT IS EXEMPT OR IMMUNE FROM EXECUTION; (III) THAT THE ACTION IS BROUGHT IN AN INCONVENIENT FORUM; OR (IV) THAT THE VENUE FOR THE ACTION IS IN ANY WAY IMPROPER.</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">THE INTERMEDIARY AGREES THAT FOR ALL PURPOSES,
      INCLUDING SECTION 8-110(e) OF THE NEW YORK UCC AND SECTION 357 OF THE FEDERAL BOOK-ENTRY REGULATIONS, THE STATE OF NEW YORK SHALL BE THE &#8220;<b>SECURITIES INTERMEDIARY&#8217;S JURISDICTION</b>&#8221;.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 13. &#160;&#160;&#160;&#160;&#160;&#160;<u>Entire Agreement</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">This Agreement and the other agreements referred to
      herein constitute all of the agreements among the parties relating to the matters set forth herein and supersede all other prior or concurrent oral or written letters, agreements or understandings with respect to the matters set forth herein.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 14. &#160;&#160;&#160;&#160;&#160;&#160;<u>Full Force and Effect</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Except as modified by this Agreement and the other
      Defeasance Documents, the Mortgage Loan Documents shall remain unchanged and in full force and effect.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 15.&#160;&#160;&#160;&#160;&#160;&#160; <u>Electronic Signatures;
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">This Agreement shall be valid, binding, and enforceable
      against a party when executed and delivered by an authorized individual on behalf of the party by means of (i) an original manual signature; (ii) a faxed, scanned, or photocopied manual signature, or (iii) any other electronic signature permitted by
      the federal Electronic Signatures in Global and National Commerce Act, state enactments of the Uniform Electronic Transactions Act, and/or any other relevant electronic signatures law, including any relevant provisions of the Code (collectively, &#8220;<b>Signature
        Law</b>&#8221;), in each case to the extent applicable. Each faxed, scanned, or photocopied manual signature, or other electronic signature, shall for all purposes have the same validity, legal effect, and admissibility in evidence as an original manual
      signature. Each party hereto shall be entitled to conclusively rely upon, and shall have no liability with respect to, any faxed, scanned, or photocopied manual signature, or other electronic signature, of any other party and shall have no duty to
      investigate, confirm or otherwise verify the validity or authenticity thereof. This Agreement may be executed in any number of counterparts, each of which shall be deemed to be an original, but such counterparts shall, together, constitute one and
      the same instrument. For the avoidance of doubt, original manual signatures shall be used for execution or indorsement of writings when required under the Code or other Signature Law due to the character or intended character of the writings.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 16. &#160;&#160;&#160;&#160;&#160;&#160;<u>Waiver Of Trial By Jury</u>. </b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">ORIGINAL BORROWER, LENDER, SUCCESSOR BORROWER, SERVICER
      AND INTERMEDIARY EACH HEREBY AGREES NOT TO ELECT A TRIAL BY JURY OF ANY ISSUE TRIABLE OF RIGHT BY JURY, AND WAIVES ANY RIGHT TO TRIAL BY JURY FULLY TO THE EXTENT THAT ANY SUCH RIGHT SHALL NOW OR HEREAFTER MAY EXIST WITH REGARD TO THIS AGREEMENT OR
      ANY DOCUMENT RELATED HERETO, OR ANY CLAIM, COUNTERCLAIM OR OTHER ACTION ARISING IN CONNECTION THEREWITH. THIS WAIVER OF RIGHT TO TRIAL BY JURY IS GIVEN KNOWINGLY AND VOLUNTARILY BY ORIGINAL BORROWER, LENDER, SUCCESSOR BORROWER, SERVICER AND
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      given in accordance with Section 14 of the Pledge Agreement, and shall be sent to Successor Borrower and Servicer at the following addresses:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse" cellpadding="0" cellspacing="0">

      <tr style="vertical-align: top">
        <td style="width: 5%">&#160;</td>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">DHC UBSCM 17 C3 Successor Borrower-R, LLC&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">11121 Carmel Commons Boulevard, Suite 250&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Charlotte, North Carolina 28226&#160;</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attention: Asset Manager&#160;</font></p>
        </td>
      </tr>
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        <td>&#160;</td>
        <td style="font-size: 10pt">&#160;</td>
        <td>&#160;</td>
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        <td>&#160;</td>
        <td style="font-size: 10pt"><font style="font-family: Times New Roman, Times, Serif;">Servicer:</font></td>
        <td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-align: right; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT HAVE BEEN
        OMITTED AND REPLACED WITH &#8220;[***]&#8221;. SUCH IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS (I) NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.</b></font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-align: center"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>THIS DEFEASANCE ACCOUNT AGREEMENT</b> (this &#8220;<b>Agreement</b>&#8221;)


      is entered into as of October 20, 2022 by and among <font style="text-transform: uppercase"><b>IONIS GAZELLE, LLC</b></font>, a Delaware limited liability company (&#8220;<b>Original Borrower</b>&#8221;), <b>U.S. BANK TRUST COMPANY, NATIONAL ASSOCIATION</b>, a
      national banking association, as Securities Intermediary and Custodian (together with its permitted successors and assigns, &#8220;<b>Intermediary</b>&#8221;), <b>U.S. BANK NATIONAL ASSOCIATION</b>, a national banking association (&#8220;<b>Account Bank</b>&#8221;), <b>WELLS


        FARGO BANK, NATIONAL ASSOCIATION, AS TRUSTEE FOR THE BENEFIT OF THE REGISTERED HOLDERS OF UBS COMMERCIAL MORTGAGE TRUST 2017-C3, COMMERCIAL MORTGAGE PASS-THROUGH CERTIFICATES, SERIES 2017-C3</b>, as secured party (together with its successors and
      assigns, &#8220;<b>Lender</b>&#8221;), and <b>MIDLAND LOAN SERVICES</b>, a division of PNC Bank, National Association (&#8220;<b>Servicer</b>&#8221;), as Master Servicer on behalf of said Trustee under the Pooling and Servicing Agreement (as hereinafter defined).</font></p>
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  <p style="font: bold 10pt Times New Roman,Times,serif; margin-top: 0px; margin-bottom: 0pt; margin-left: 0px; text-align: center; text-indent: 0in;"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">RECITALS<font style="font-variant: small-caps">:</font></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-align: center; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">A.&#160;&#160;&#160;&#160;&#160;&#160;&#160;UBS AG, by and through its branch office at 1285
      Avenue of the Americas, New York, New York (&#8220;<b>Original Lender</b>&#8221;), made a loan (the &#8220;<b>Mortgage Loan</b>&#8221;) to Original Borrower in the original principal amount of $51,350,000.00, made pursuant to a Loan Agreement dated July 18, 2017 (the &#8220;<b>Loan


        Agreement</b>&#8221;), and evidenced by (1) a Promissory Note A-1 dated July 18, 2017 in the original principal amount of $36,350,000.00 (the &#8220;<b>Note A-1</b>&#8221;), (2) a Promissory Note A-2 dated July 18, 2017 in the original principal amount of
      $5,000,000.00 (the &#8220;<b>Note A-2</b>&#8221;), and (3) a Promissory Note A-3 dated July 18, 2017 in the original principal amount of $10,000,000.00 (Note A-1, Note A-2 and Note A-3 are, individually and collectively, the &#8220;<b>Note</b>&#8221; or the &#8220;<b>Notes</b>&#8221;).</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">B.&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Mortgage Loan and the Notes are secured by,
      among other things, a Deed of Trust and Security Agreement dated July 18, 2017 from Original Borrower to and for the benefit of Original Lender (the &#8220;<b>Security Instrument</b>&#8221;), which grants to Original Lender, among other things, a lien on the
      real and personal property described in said Security Instrument (the &#8220;<b>Mortgaged Property</b>&#8221;). The Mortgage Loan is further evidenced or secured by various other documents, including guaranties, executed by Original Borrower and others in favor
      of Original Lender (together with the Notes, the Loan Agreement and the Security Instrument, the &#8220;<b>Mortgage Loan Documents</b>&#8221;).</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">C.&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Lender assigned all of its right, title
      and interest in the Mortgage Loan and the Mortgage Loan Documents (by one or more assignments) to Lender in connection with the issuance of UBS Commercial Mortgage Trust 2017-C3, Commercial Mortgage Pass-Through Certificates, Series 2017-C3 (the &#8220;<b>Certificates</b>&#8221;).


      Lender is the current holder of the Notes and the owner of the Mortgage Loan and the Mortgage Loan Documents.</font></p>
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      Pooling and Servicing Agreement dated as of August 1, 2017 (as from time to time amended, supplemented or modified, the &#8220;<b>Pooling and Servicing Agreement</b>&#8221;).</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">E.&#160;&#160;&#160;&#160;&#160;&#160;&#160;Original Borrower, Lender, and Intermediary have
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      Agreement (the &#8220;<b>Securities</b>&#8221;) and other assets that, together with the Securities, constitute the Pledged Collateral (as defined in the Pledge Agreement).</font></p>
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      execution of this Agreement, Original Borrower, Lender, Servicer, Intermediary, and DHC UBSCM 17 C3 Successor Borrower-R, LLC, a Delaware limited liability company (&#8220;<b>Successor Borrower</b>&#8221;), will enter into the Defeasance Assignment, Assumption
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  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;1.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Definitions</u>.</b></font></td>
      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Scheduled Payment Date</b>&#8221; means November 6, 2022
      and the sixth (6<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup>) day of each calendar month thereafter through and including the Final Payment Date. If any payment required under this Agreement is due on a date
      that is not a Business Day, then such payment shall be made on the immediately preceding Business Day.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Securities Intermediary</b>&#8221; means a &#8220;securities
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#8220;<b>Tax Identification Number</b>&#8221; means the federal tax
      identification number of Successor Borrower, which number is 83-2813361.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;2.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Establishment and Custody of Pledged Collateral Account</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Intermediary has established the Pledged Collateral
      Account at Intermediary (or at the Account Bank set forth on <b><u>Addendum 1</u></b>, if any, which <b><u>Addendum 1</u></b> the parties hereto agree functions as an amendment to this Agreement), which is a Securities Account maintained in the
      name of Lender as entitlement holder. Each party hereto hereby authorizes, appoints and directs Intermediary to act as Securities Intermediary with respect to the Pledged Collateral and as Custodian of the Pledged Collateral Account (subject to the
      terms and conditions of the Pledge Agreement and this Agreement), and to maintain the Pledged Collateral Account subject to the sole dominion and control (as defined in Section&#160;8-106 of the Code) of Lender. Intermediary, or Account Bank, as
      applicable, agrees for so long as it remains Securities Intermediary to maintain the Pledged Collateral Account and all of the Pledged Collateral at its office currently located in Phoenix, Arizona, provided however, if Intermediary intends to move
      the Pledged Collateral Account to another location, it shall provide Lender with not less than thirty (30) days prior written notice and Intermediary shall cooperate with Lender at Intermediary&#8217;s sole cost and expense in ensuring Lender&#8217;s continuing
      perfected security interest in the Pledged Collateral Account as required under the Code, including without limitation, the execution of any and all documents required to continue Lender&#8217;s perfected security interest in the Pledged Collateral
      Account. Intermediary agrees to serve as Securities Intermediary with respect to the Securities and the other Pledged Collateral and as Custodian with respect to the Pledged Collateral Account in accordance with this Agreement and the Pledge
      Agreement. Notwithstanding anything to the contrary contained herein, Pledgor and Intermediary agree that New York is Intermediary&#8217;s jurisdiction for purposes of the Code.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">4</font></div>
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  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;3.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Title to Pledged Collateral</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Title to the Pledged Collateral shall be held in
      accordance with the Pledge Agreement and the Federal Book-Entry Regulations.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 4.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Intermediary&#8217;s Duties Regarding Pledged Collateral</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Administration</u>. Intermediary shall have
      no responsibility for supervision or management of the Pledged Collateral except as provided in this Agreement, the Pledge Agreement or as otherwise provided by applicable law. The Pledged Collateral Account shall at all times be maintained as a
      segregated Eligible Account. Each item of property at any time credited to the Pledged Collateral Account shall be treated by Intermediary as a Financial Asset. Proceeds of the Pledged Collateral, and interest and earnings thereon, shall be credited
      to and held in the Pledged Collateral Account, and shall be re-invested only in accordance with this Agreement. Intermediary&#8217;s responsibility with regard to the sale, purchase, exchange or other matters relating to any assets at any time in the
      Pledged Collateral Account shall be limited to following all written orders, including Entitlement Orders, of Servicer (on behalf of Lender) promptly upon receipt thereof, without the need for consent by Pledgor or any other Person. In connection
      with the execution and delivery of the Defeasance Assumption Agreement by Successor Borrower, the Pledged Collateral Account shall be assigned the Tax Identification Number, and all taxable income earned or gain realized with respect to the Pledged
      Collateral shall be taxable as income or gain, as applicable, and reported under the Tax Identification Number.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Eligible Institution</u>. Intermediary shall
      at all times serve as both Securities Intermediary and Custodian hereunder. Intermediary is and shall at all times continue to be, and the Pledged Collateral Account shall at all times be maintained with, an Eligible Institution. Upon any downgrade,
      withdrawal, qualification or suspension by any Rating Agency of the rating of Intermediary or any other circumstances resulting in a failure to qualify as an Eligible Institution, (i)&#160;the Pledged Collateral Account and all of the Pledged Collateral,
      and all rights and obligations of Intermediary under this Agreement, shall promptly, and in any case within thirty (30) calendar days, be moved to an Eligible Institution that is a Securities Intermediary and Custodian approved by Lender that
      maintains a Participant&#8217;s Securities Account with the Federal Reserve Bank; (ii)&#160;such Eligible Institution shall assume in writing all obligations of Intermediary under this Agreement; and (iii)&#160;Intermediary shall promptly reimburse Lender and
      Servicer for all expenses incurred in connection with the appointment of such Eligible Institution as successor to Intermediary, including the full reasonable price charged by such successor to Intermediary to deliver all services provided for by
      this Agreement through the Final Payment Date.</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">5</font></div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Reinvestment of Proceeds; Permitted
        Investments</u>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Pledgor hereby instructs
      Servicer, and Servicer hereby instructs Intermediary, to invest funds in the Pledged Collateral Account in the Default Permitted Investment unless and until different instructions are received in accordance with this <b><u>Subsection&#160;(c)</u></b> or
      until Servicer has determined that the Default Permitted Investment is not a Permitted Investment, and has provided new investment instructions to Intermediary. Intermediary shall have no obligation to invest funds in the Pledged Collateral Account
      (other than in the Default Permitted Investment as provided above) absent receipt of written instructions from Servicer or except as otherwise provided in this Agreement. Intermediary hereby certifies that, as of the date of this Agreement, the
      Default Permitted Investment constitutes a Permitted Investment.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Upon the written request of
      Pledgor (which request may be made not more than once per month), Servicer agrees to direct Intermediary to invest and reinvest any funds in the Pledged Collateral Account from time to time in Permitted Investments as instructed by Pledgor, <u>provided</u>,
      <u>however</u>, that if an Event of Default shall have occurred, Servicer may direct Intermediary to invest and reinvest such funds in such Permitted Investments as Servicer shall determine in Servicer&#8217;s discretion. Intermediary shall only be
      required to follow the written investment instructions that were most recently received by Servicer, and Pledgor shall be bound by such last received investment instructions. Any request from Pledgor containing investment instructions (except the
      instruction to invest in Default Permitted Investments as provided herein) shall contain an officer&#8217;s certificate from Pledgor (which may be conclusively relied upon by Servicer, Intermediary and their agents) that any such investments constitute
      Permitted Investments. Intermediary shall have three (3) Business Days following receipt of such instructions to effectuate such investment direction. Intermediary may conclusively rely upon the investment instructions received from Servicer.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Permitted Investments shall be
      selected that mature (unless payable on demand) not later than one (1) Business Day before the date such funds are required to be distributed pursuant to <b><u>Section&#160;4(e)</u></b> of this Agreement. To the extent any funds in the Pledged Collateral
      Account will be necessary to make payments to the Collection Account more than three (3) months after the related Securities were converted to cash, such funds shall be invested only in obligations of, or obligations guaranteed as to principal and
      interest by, the United States or an agency or instrumentality thereof, backed by the full faith and credit of the United States. In no event shall such funds be applied to debt service on the Mortgage Loan more than four (4) months after being
      converted to cash, except as provided in the Accountant&#8217;s Report. All Permitted Investments shall be held to maturity unless payable on demand, in which case Intermediary shall demand payment as necessary to meet the payment requirements of <b><u>Section&#160;4(e)</u></b>.
      All earnings and payments received with respect to Permitted Investments shall be credited to and held in the Pledged Collateral Account in accordance with this Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iv)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; If a requested Permitted Investment
      is determined to be, in the reasonable judgment of Servicer, an investment for which confirmation from one or more of the Rating Agencies is required, Servicer shall, within three (3) Business Days of receipt of the required confirmation from the
      Rating Agencies, provide instructions to Intermediary authorizing such Permitted Investment. Servicer shall not be required to request confirmation from any Rating Agency without written instructions from Pledgor and receipt of reasonable assurances
      from Pledgor that Servicer shall be reimbursed for costs associated with such Rating Agency confirmation. Pledgor shall be responsible for paying all costs associated with obtaining such Rating Agency confirmation, including, but not limited to,
      Servicer fees and Rating Agency fees.</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">6</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(v)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; With respect to all investments
      made on instructions of Pledgor, Pledgor shall be liable for (1)&#160;ordinary and customary transaction fees associated with the investment of funds in the Pledged Collateral Account except as provided in <b><u>Section&#160;9</u></b> hereof, and (2)&#160;losses
      that result from such investment. Pledgor shall pay such fees or reimburse Lender for such investment losses within five (5) Business Days after receipt of written request or invoice therefor.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(vi)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; All Permitted Investments shall be
      under the sole dominion and control of Lender. No Permitted Investment shall be made unless Lender holds a first priority perfected lien in such Permitted Investment and all filings and other actions necessary to ensure the validity, perfection, and
      priority of such lien have been taken. Notwithstanding the foregoing, Intermediary will have no responsibility for losses on the investments made in accordance with written instruction. Lender, Servicer, and Intermediary shall have no responsibility
      or liability for losses on any investments made under instructions authorized in this subsection (c) or in accordance with the other procedures provided for herein, or for losses on any Default Permitted Investments authorized under this Agreement.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0.5in; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Collection of Interest, Principal and
        Earnings</u>. All interest and principal when due from any Obligor with respect to the Pledged Collateral, and all amounts due with respect to Permitted Investments shall be paid to Intermediary. Intermediary shall deposit all amounts received with
      respect to Pledged Collateral and Permitted Investments to the Pledged Collateral Account, but shall be under no responsibility or duty to undertake collection efforts or to instigate or participate in any legal proceedings or to retain counsel in an
      effort to accomplish such collection. All revenues received in any collection action shall be deposited to the Pledged Collateral Account and disposed of as set forth herein.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Distributions</u>. Lender, acting by and
      through Servicer as herein provided, shall have the sole right to direct distributions from the Pledged Collateral Account. Except as otherwise specifically provided in written instructions given in accordance with <b><u>Section&#160;5</u></b> below,
      Intermediary shall, to the extent of funds on deposit in the Pledged Collateral Account, make the applicable payment to the applicable Collection Account by wire or internal transfer, beginning on the first Scheduled Payment Date and continuing
      thereafter on each Scheduled Payment Date until the Final Payment Date, as follows:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">in an amount equal to the A-1 Scheduled Monthly Payment to the A-1 Collection Account,</font></td>
      </tr>

  </table>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">in an amount equal to the A-2 Scheduled Monthly Payment to the A-2 Collection Account, and</font></td>
      </tr>

  </table>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">in an amount equal to the A-3 Scheduled Monthly Payment to the A-3 Collection Account</font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">On the Final Payment Date, Intermediary shall pay, by
      wire or internal transfer, an amount equal to the applicable Pay-Off Amount as set forth in the applicable Note and shown in the Accountant&#8217;s Report, as follows:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(i)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">the A-1 Pay-Off Amount to the A-1 Collection Account,</font></td>
      </tr>

  </table>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(ii)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">the A-2 Pay-Off Amount to the A-2 Collection Account, and</font></td>
      </tr>

  </table>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 12pt">

      <tr style="vertical-align: top">
        <td style="width: 1in"></td>
        <td style="width: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(iii)</font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">the A-3 Pay-Off Amount to the A-3 Collection Account.</font></td>
      </tr>

  </table>
  <div class="BRPFPageBreakArea" style="margin-bottom: 0; clear: both; margin-top: 0">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">7</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Any amounts remaining in the Pledged Collateral Account
      after payments are made to the applicable Collection Accounts pursuant to the preceding sentence shall be held in the Pledged Collateral Account until after the final payment of all amounts required under the Notes and other Defeasance Documents on
      account of the Secured Obligations have been paid, whereupon any amounts remaining in the Pledged Collateral Account shall be paid over to Successor Borrower within ten (10) Business Days (or any other mutually agreed upon date) provided the
      Intermediary has not been notified that an Event of Default that could result in personal liability of the Successor Borrower exists under any other Pool Defeasance Documents. If any payment required under this Agreement is due on a date that is not
      a Business Day, then such payment shall be made on the immediately preceding Business Day.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Default</u>. Lender shall have all of the
      rights and remedies afforded under the Pledge Agreement or otherwise, at law or in equity, with respect to any default under this Agreement. Without limiting the generality of the foregoing, if Intermediary fails to make any of the foregoing payments
      as instructed herein when funds are available for such payment in the Pledged Collateral Account or otherwise fails to fully and timely perform any material obligations of Intermediary hereunder and such failure to perform such material obligations
      results in material financial damage to the Lender, Intermediary shall be liable to Lender for any fees, costs, expenses or other damages incurred by Lender as a result thereof, including but not limited to default interest and late fees accruing
      under the Note, together with reasonable attorneys&#8217; fees incurred by Lender to enforce its rights under the Defeasance Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;5.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Instructions; Signatures</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>From Servicer</u>. All instructions and
      directions from Servicer to Intermediary for the Pledged Collateral Account must be in writing, signed by a person or persons duly authorized by Servicer on behalf of Lender to sign. Such instructions to be in such form as Intermediary may reasonably
      require, and shall be accompanied by such evidence of authority as Intermediary may reasonably require.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>From Successor Borrower</u>. After the
      contemplated assignment by Original Borrower to Successor Borrower, all instructions and directions from Successor Borrower to Servicer for the Pledged Collateral Account must be in writing, signed by a person or persons duly authorized by Successor
      Borrower to sign. Such instructions shall be in such form as reasonably required by Servicer, and shall be accompanied by such evidence of authority as Servicer may reasonably require.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;6.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Accounting</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Intermediary shall (a)&#160;keep complete and accurate books
      of the Pledged Collateral Account and all Permitted Investments showing all receipts, disbursements and transactions in the Pledged Collateral Account; (b)&#160;prepare and deliver via electronic means to Successor Borrower and Servicer, on or before the
      last day of each month, a monthly report summarizing all transactional activity in the Pledged Collateral Account for the preceding calendar month; and (c)&#160;advise Successor Borrower and Servicer of any non-payment by an Obligor of principal or
      interest on account of the Pledged Collateral within two (2) Business Days of the related payment date.&#160; Successor Borrower agrees that it shall assume the obligation to prepare and file all required state and federal tax reports and returns, and to
      pay any taxes related to its ownership of the assets in the Pledged Collateral Account, and that all such taxes shall be paid from sources other than the Pledged Collateral. Pledgor, Successor Borrower and Servicer acknowledge that to the extent
      regulations of the Comptroller of the Currency or other applicable regulatory entity grant Pledgor, Successor Borrower and Servicer the right to receive brokerage confirmations of security transactions as they occur, Pledgor and Servicer specifically
      waive receipt of such confirmations to the extent permitted by law.</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">8</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;7.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Termination</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0in"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Lender may, at its expense, terminate this Agreement at
      any time by giving thirty (30) days prior written notice to the other parties hereto; provided that upon doing so, Lender shall enter into a new Account Agreement with Pledgor upon terms materially similar to this Agreement. Lender may, at its
      expense, without terminating this Agreement, replace or substitute an Eligible Institution for Intermediary at any time with or without cause by giving thirty (30) days prior written notice to the other parties hereto. Upon any material default by
      Intermediary in its obligations under the Defeasance Documents or if any representation of Intermediary shall prove to have been inaccurate or incomplete in any material respect when made or the State of New York shall at any time not be the
      &#8220;securities intermediary&#8217;s jurisdiction&#8221; under Section 8.110(e) of the Code and Section 357 of the Federal Book-Entry Regulations, Lender may, if such default or failure of a representation shall not have been cured within a reasonable time as
      determined by Servicer, terminate Intermediary&#8217;s rights under this Agreement immediately upon written notice to Intermediary. Intermediary may resign from its obligations under this Agreement at any time by giving thirty (30) days prior written
      notice to the other parties hereto, but in no event shall Intermediary be released of its obligations as Securities Intermediary or Custodian hereunder unless and until a substitute Eligible Institution, satisfactory to Lender in its sole and
      absolute discretion, has been designated and has assumed in writing the obligations of Intermediary hereunder at the sole cost and expense of the resigning Intermediary. Lender shall designate a substitute Intermediary, in its sole discretion,
      promptly after receipt of notice of resignation by Intermediary and shall take all reasonable actions necessary to cause such designated successor to promptly assume the obligations of Intermediary hereunder. Intermediary may assign or transfer its
      obligations to an Eligible Institution, satisfactory to Lender in its sole and absolute discretion, by giving thirty (30) days prior written notice to Lender and Servicer. Unless Lender elects to terminate this Agreement pursuant to the first
      sentence of this <b><u>Section 7</u></b> or replace Intermediary pursuant to the second sentence of this <b><u>Section 7</u></b>, all costs and expenses incurred in connection with (a) the transfer of Securities to a successor to Intermediary and
      (b) the assumption of the obligations of Intermediary by such successor shall be borne by Intermediary. In any event, if Intermediary is replaced pursuant to this <b><u>Section 7</u></b>, other than pursuant to the first two sentences of this <b><u>Section


          7</u></b>, Intermediary shall reimburse Lender for all expenses incurred in connection with the appointment of such Eligible Institution as successor to Intermediary, including the full reasonable price charged by such successor to Intermediary
      to deliver all services provided for by this Agreement through the Final Payment Date.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;8.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Authority</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Any Person executing this Agreement in a fiduciary or
      other representative capacity represents that such party has full power and authority to do so and that any applicable or required court, limited liability company, partnership, corporate or other authority has been duly and properly given and
      continues as of the date hereof.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;9.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Fees and Costs</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Concurrently with the execution of this Agreement,
      Original Borrower shall pay (a) the Servicer Processing Fee to Servicer as a fee in connection with the Pledged Collateral Account and the services provided hereunder by Servicer, and (b)&#160;the Intermediary Custodial Fee to Intermediary in full payment
      of all fees in connection with the Pledged Collateral Account and the services provided hereunder by Intermediary through the Final Payment Date, provided that Pledgor shall be responsible for fees and costs specified in <b><u>Section&#160;4(c)</u></b>
      above, if applicable. Intermediary and Servicer hereby acknowledge and confirm that any fees and expenses charged by the Intermediary related to investments in the Default Permitted Investment and wire transfers to the Collection Account or to the
      Pledgor are included in the fees and expenses already paid to Intermediary and Servicer, respectively, pursuant to this <b><u>Section&#160;9</u></b>, and except as provided below, Pledgor shall have no further liability for such fees and expenses as of
      the date hereof or at any time hereafter. Such fees have been fully earned by each of Servicer and Intermediary and are not refundable or subject to reduction, except as set forth in <b><u>Section&#160;4(b)(iii)</u></b>. Intermediary hereby acknowledges
      and confirms that as of the date hereof, there are no fees charged by Intermediary in connection with investments in the Default Permitted Investment. In the event Intermediary is notified that any such fees shall at any time hereafter become payable
      in connection with the Default Permitted Investment, or if there is any increase in fees payable in connection with any other Permitted Investment in which any funds included in or relating to the Pledged Collateral are invested, Intermediary shall
      promptly give written notice of such new or increased fees to Servicer and Successor Borrower. Prior to the imposition of any such new or increased fee, Successor Borrower shall have the right, in accordance with the provisions of <b><u>Section&#160;4(c)</u></b>
      hereof, to request that Servicer direct Intermediary to invest and reinvest any funds in the Pledged Collateral Account from time to time in another Permitted Investment; provided, however, that if Successor Borrower fails to provide such investment
      direction in the foregoing circumstances, Successor Borrower shall be solely responsible for the payment of all such new or increased fees. In no event shall any funds from the Pledged Collateral Account be used to pay any such fees, which shall be
      the sole responsibility of Successor Borrower.</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">9</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">If any out-of-pocket costs or expenses are reasonably
      incurred by Servicer or Intermediary in connection with the funds in the Pledged Collateral Account and the protection and preservation of Lender&#8217;s rights therein, Successor Borrower shall be responsible for the payment of all such costs and expenses
      directly to Intermediary or Servicer, as the case may be, within ten (10) Business Days following receipt of written invoice therefor.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;10.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Governing Law, Venue, Attorneys&#8217; Fees</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">THIS AGREEMENT AND THE RIGHTS AND OBLIGATIONS OF THE
      PARTIES HERETO AND THEIR SUCCESSORS AND ASSIGNS SHALL IN ALL RESPECTS BE GOVERNED BY, AND CONSTRUED AND ENFORCED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF NEW&#160;YORK (&#8220;<b>STATE</b>&#8221;), INCLUDING THE UNIFORM COMMERCIAL CODE AS ADOPTED IN THE STATE AND
      INCLUDING NEW YORK GENERAL OBLIGATIONS LAW SECTIONS&#160;5-1401 AND 5-1402 BUT OTHERWISE WITHOUT REGARD TO LAWS OF THE STATE CONCERNING CONFLICTS OF LAWS OR CHOICE OF FORUM. IN THE EVENT OF ANY DISPUTE REGARDING THIS AGREEMENT, THE PARTIES AGREE THAT THE
      PREVAILING PARTY SHALL BE ENTITLED TO SUCH COSTS AND ATTORNEYS&#8217; FEES AS THE COURT MAY ADJUDGE REASONABLE.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">PLEDGOR, LENDER, SERVICER AND INTERMEDIARY HEREBY
      IRREVOCABLY SUBMIT TO PERSONAL JURISDICTION IN THE STATE AND TO THE NON-EXCLUSIVE JURISDICTION OF ANY NEW YORK STATE OR FEDERAL COURT SITTING IN THE CITY OF NEW YORK OVER ANY SUIT, ACTION OR PROCEEDING ARISING OUT OF OR RELATING TO THIS AGREEMENT.
      JURISDICTION AND VENUE OF ANY ACTION BROUGHT TO ENFORCE THIS AGREEMENT OR ANY OTHER DEFEASANCE DOCUMENT OR ANY ACTION RELATING TO THE TRANSACTIONS CONTEMPLATED HEREBY OR THE RELATIONSHIPS CREATED BY OR UNDER THE DEFEASANCE DOCUMENTS (&#8220;<b>ACTION</b>&#8221;)
      SHALL, AT THE ELECTION OF LENDER, BE IN (AND IF ANY ACTION IS ORIGINALLY BROUGHT IN ANOTHER VENUE, THE ACTION SHALL AT THE ELECTION OF LENDER BE TRANSFERRED TO) A STATE OR FEDERAL COURT OF APPROPRIATE JURISDICTION LOCATED IN THE STATE. PLEDGOR,
      LENDER, SERVICER AND INTERMEDIARY HEREBY CONSENT AND SUBMIT TO THE PERSONAL JURISDICTION OF THE COURTS OF THE STATE AND OF FEDERAL COURTS LOCATED IN THE STATE IN CONNECTION WITH ANY ACTION AND HEREBY WAIVE ANY AND ALL PERSONAL RIGHTS UNDER THE LAWS
      OF ANY OTHER STATE TO OBJECT TO JURISDICTION WITHIN THE STATE FOR PURPOSES OF ANY ACTION. PLEDGOR, LENDER, SERVICER AND INTERMEDIARY HEREBY WAIVE AND AGREE NOT TO ASSERT, AS A DEFENSE TO ANY ACTION OR A MOTION TO TRANSFER VENUE OF ANY ACTION, (A)&#160;ANY
      CLAIM THAT IT IS NOT SUBJECT TO SUCH JURISDICTION; (B)&#160;ANY CLAIM THAT ANY ACTION MAY NOT BE BROUGHT AGAINST IT OR IS NOT MAINTAINABLE IN THOSE COURTS OR THAT THIS AGREEMENT MAY NOT BE ENFORCED IN OR BY THOSE COURTS, OR THAT IT IS EXEMPT OR IMMUNE
      FROM EXECUTION; (C)&#160;THAT THE ACTION IS BROUGHT IN AN INCONVENIENT FORUM; OR (D) THAT THE VENUE FOR THE ACTION IS IN ANY WAY IMPROPER.</font></p>
  <div class="BRPFPageBreakArea" style="MARGIN-BOTTOM: 10pt; CLEAR: both; MARGIN-TOP: 10pt">
    <div class="BRPFPageNumberArea" style="TEXT-ALIGN: center"><font style="font-size: 8pt; font-family: 'Times New Roman',Times,serif; font-weight: normal; color: rgb(0, 0, 0); font-style: normal;">10</font></div>
    <div class="BRPFPageBreak" style="PAGE-BREAK-AFTER: always">
      <hr noshade="noshade" style="BORDER-LEFT-WIDTH: 0px; HEIGHT: 2px; BORDER-RIGHT-WIDTH: 0px; WIDTH: 100%; BORDER-BOTTOM-WIDTH: 0px; COLOR: #000000; CLEAR: both; MARGIN: 4px 0px; BORDER-TOP-WIDTH: 0px; BACKGROUND-COLOR: #000000"> </div>
  </div>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">INTERMEDIARY AGREES THAT FOR ALL PURPOSES, INCLUDING
      SECTION&#160;8-110(e) OF THE NEW YORK UCC AND SECTION&#160;357 OF THE FEDERAL BOOK-ENTRY REGULATIONS, THE STATE OF NEW YORK SHALL BE THE &#8220;<b>SECURITIES INTERMEDIARY&#8217;S JURISDICTION</b>&#8221;.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;11.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Severability of Provisions</u>. </b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Any provision of this Agreement which is prohibited or
      unenforceable in any jurisdiction shall, as to such jurisdiction, be ineffective to the extent of such prohibition or unenforceability without invalidating the remaining provisions hereof or affecting the validity or enforceability of such provision
      in any other jurisdiction.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;12.</b></font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pledgor agrees to indemnify Lender, Intermediary
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      against all Claims, including, without limitation, the reasonable fees and disbursements of counsel, which may be incurred by any Indemnitee in connection with Pledgor&#8217;s or Indemnitee&#8217;s actions or failure to act hereunder or in connection with any
      investigative, administrative or judicial proceedings (whether or not such Indemnitee shall be designated a party thereto) relating to or arising out of the Pledged Collateral, this Agreement or the other Defeasance Documents (including, without
      limitation, any such proceeding by Pledgor against any Indemnitee or by any Indemnitee against Pledgor to the extent that Indemnitee is the prevailing party); <u>provided</u> that no Indemnitee shall have the right to be indemnified hereunder for
      its own gross negligence or willful misconduct (and with respect to Intermediary, its own negligence) as finally determined by a court of competent jurisdiction. The provisions of this <b><u>Section 13</u></b> shall survive the termination of this
      Agreement and the removal or resignation of Intermediary or Servicer.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" border="0" style="width: 100%; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif">

      <tr style="vertical-align: top">
        <td style="width: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section&#160;14.</b></font></td>
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      </tr>

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      against a party when executed and delivered by an authorized individual on behalf of the party by means of (i) an original manual signature; (ii) a faxed, scanned, or photocopied manual signature, or (iii) any other electronic signature permitted by
      the federal Electronic Signatures in Global and National Commerce Act, state enactments of the Uniform Electronic Transactions Act, and/or any other relevant electronic signatures law, including any relevant provisions of the Code (collectively, &#8220;<b>Signature


        Law</b>&#8221;), in each case to the extent applicable. Each faxed, scanned, or photocopied manual signature, or other electronic signature, shall for all purposes have the same validity, legal effect, and admissibility in evidence as an original manual
      signature. Each party hereto shall be entitled to conclusively rely upon, and shall have no liability with respect to, any faxed, scanned, or photocopied manual signature, or other electronic signature, of any other party and shall have no duty to
      investigate, confirm or otherwise verify the validity or authenticity thereof. This Agreement may be executed in any number of counterparts, each of which shall be deemed to be an original, but such counterparts shall, together, constitute one and
      the same instrument. For the avoidance of doubt, original manual signatures shall be used for execution or indorsement of writings when required under the Code or other Signature Law due to the character or intended character of the writings.</font></p>
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      <tr style="vertical-align: top; text-align: justify">
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        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Successors and Assigns</u>.</b></font></td>
      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">This Agreement shall be binding upon and, subject to the
      restrictions on assignment by Pledgor set forth in the Pledge Agreement, shall inure to the benefit of the successors and assigns of the parties hereto. Lender shall have the right to assign or transfer rights and obligations under this Agreement
      without limitation. Any assignee or transferee shall be entitled to all the benefits afforded Lender under this Agreement; <u>provided</u>, that such assignee or transferee shall have delivered to the other parties hereto written confirmation that
      such assignee and transferee agrees to be bound by the terms of this Agreement and is also the assignee or transferee of the Defeasance Documents.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Intermediary shall have the right to assign or transfer
      its rights and obligations hereunder only in connection with a termination or with the prior written consent of Lender, as set forth in <b><u>Section 7</u></b>.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Pledgor shall have the right to assign and transfer its
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 16.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Notices</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">All notices and other communications hereunder by any
      party to any other party shall be given in accordance with Section&#160;14 of the Pledge Agreement. Notices and other communications to Servicer shall be sent to the following address:</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="width: 100%; font: 10pt Times New Roman, Times, Serif; border-collapse: collapse">

      <tr style="vertical-align: top">
        <td style="width: 50%; padding-right: 5.4pt; padding-left: 5.4pt; font-size: 10"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></td>
        <td style="width: 50%; padding-right: 5.4pt; padding-left: 5.4pt">
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Midland Loan Services,</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">a division of PNC Bank, National Association</font></p>
          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">10851 Mastin Boulevard, Suite 700</font></p>
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          <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">Attention: Asset Management</font></p>
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        </td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 17.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Modification in Writing</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">This Agreement, and any provisions hereof, may not be
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 18.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Waiver of Trial by Jury</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in"><font style="font: 10pt Times New Roman, Times, Serif"><b></b></font></p>
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      <tr style="vertical-align: top; text-align: justify">
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        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 19.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Rights and Protections of the Intermediary</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">All rights and protections of the Intermediary as set
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
        <td style="width: 1in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>Section 20.</b></font></td>
        <td><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b><u>Tax Reporting</u>.</b></font></td>
      </tr>

  </table>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 1in; text-indent: -1in">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">For the avoidance of doubt, the Pledged Collateral
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
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      </tr>

  </table>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
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      <tr style="vertical-align: top; text-align: justify">
        <td style="width: 0in"></td>
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      </tr>

  </table>
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      and the Defeasance Documents (including payments of each of the Mortgage Loans in full on the Final Payment Date), then any payment, whether principal or interest, under any of the Notes and any proceeds from the sale of the Pledged Collateral will
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  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;</p>
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      Agreement as of the date first above written.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 0; text-indent: 0.5in">&#160;&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin-top: 0; margin-bottom: 0pt; margin-left: 3in; text-indent: -3in"></p>
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      <tr style="vertical-align: top">
        <td style="padding-right: 5.4pt; padding-left: 0"><font style="font-variant: small-caps"><b>Original Borrower</b></font><b>:</b></td>
        <td style="padding-right: 5.4pt; padding-left: 0" colspan="3"><b>IONIS GAZELLE, LLC</b>,<br>
          a Delaware limited liability company</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-right: 5.4pt; padding-left: 0">&#160;</td>
        <td style="padding-right: 5.4pt; padding-left: 0" colspan="3">&#160;</td>
      </tr>
      <tr style="vertical-align: top">
        <td style="padding-right: 5.4pt; padding-left: 0">&#160;</td>
        <td style="padding-right: 5.4pt; padding-left: 0">By:</td>
        <td style="padding-right: 5.4pt; padding-left: 0" colspan="2">Ionis Pharmaceuticals, Inc., <br>
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<DOCUMENT>
<TYPE>EX-10.80
<SEQUENCE>13
<FILENAME>exhibit10-80.htm
<DESCRIPTION>EXHIBIT 10.80
<TEXT>
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      <div style="text-align: right; font-weight: bold;">Exhibit 10.80</div>
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      <div style="color: rgb(0, 0, 0); font-weight: bold; text-align: justify;">CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT HAVE BEEN OMITTED AND REPLACED WITH &#8220;[***]&#8221;. SUCH IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS BOTH
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      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.15pt; font-weight: bold;">COLLABORATION AND LICENSE AGREEMENT</div>
      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.15pt; font-weight: bold;"> <br>
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      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.15pt; font-weight: bold;">BETWEEN</div>
      <div>&#160;</div>
      <div style="text-align: center; margin-right: 114.2pt; margin-left: 123.2pt; font-variant: small-caps; font-weight: bold;">Metagenomi, Inc.</div>
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      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.05pt; font-weight: bold;">AND</div>
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      <div style="text-align: center; margin-right: 114.2pt; margin-left: 123.2pt; font-variant: small-caps; font-weight: bold;">Ionis Pharmaceuticals, Inc.</div>
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      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.15pt; font-variant: small-caps; font-weight: bold;">Dated November 10, 2022</div>
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      <div style="text-align: center; margin-right: 114.2pt; margin-left: 123.2pt; font-weight: bold;">TABLE OF CONTENTS</div>
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            <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
            <td style="width: 5%; vertical-align: top; text-align: right;" rowspan="1"><font style="font-weight: bold;">Page</font></td>
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          <tr>
            <td style="vertical-align: top;" colspan="2" rowspan="1">&#160;</td>
            <td style="width: 5%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
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          <tr>
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              <div>Article 1 Overview</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">1</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">1.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Drug Discovery Program</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">1</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">1.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Development and Commercialization</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">1</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">1.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Co-Development and Co-Commercialization</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">1</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">1.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Exploratory Research</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">1.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Governance</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">1.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Purpose</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div>Article 2 Collaboration</div>
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            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">2.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Selection of Collaboration Targets</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">2</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">2.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Drug Discovery Program</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">5<br>
              </div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">2.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Exploratory Research Program</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">7</td>
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              <div style="margin-left: 9pt;">2.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Conduct of Collaboration Activities</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">8</td>
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              <div style="margin-left: 9pt;">2.5.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Cost of Collaboration Activities</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">8</td>
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            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">2.6.</div>
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            <td style="width: 87%; vertical-align: top;">
              <div>Collaboration Program Records and Reports</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">9</td>
          </tr>
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            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">2.7.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Ionis Proprietary Toolbox of Chemical Modifications</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">9</div>
            </td>
          </tr>
          <tr>
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              <div>Article 3 Licenses; Exclusivity</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">10</td>
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            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">3.1.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>License Grants to Ionis</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">10<br>
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            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">3.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>License Grants to Metagenomi</div>
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            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">11</div>
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            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">3.3.</div>
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              <div>Subcontractors</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">13</td>
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            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">3.4.</div>
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              <div>Technology Transfer</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">13</td>
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            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">3.5.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>No Implied Licenses</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">14</div>
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              <div style="margin-left: 9pt;">3.6.</div>
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              <div>Exclusivity</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">14</td>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">16</td>
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              <div style="margin-left: 9pt;">4.1.</div>
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              <div>Joint Steering Committee</div>
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            <td style="width: 5%; vertical-align: top; text-align: right;">16</td>
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              <div style="margin-left: 9pt;">4.2.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Subcommittees</div>
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              <div style="text-align: right;">17</div>
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              <div style="margin-left: 9pt;">4.3.</div>
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              <div>Joint Research Committee.</div>
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              <div style="text-align: right;">18</div>
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              <div style="margin-left: 9pt;">4.4.</div>
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            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Alliance Managers</div>
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            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
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          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">4.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Additional Participants</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">19</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">4.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Decision-Making</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">19</td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div>Article 5 Co-Development and Co-Commercialization Options</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">20</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">5.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Co-Develop and Co-Commercialization Options</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">20</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">5.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Development and Commercialization of the Co-Co Products; Opt-Down Right</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">21</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">5.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Escalation Procedure.</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">21</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">i</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" id="zb4c8f010344a45debfba81a4b807a5a4" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">5.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Metagenomi Opt-Out</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">21</td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div>Article 6 Development and Commercialization of the Ionis Products</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">22</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">6.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Development</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">22</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">6.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Commercialization</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">22</td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 7 Regulatory Affairs</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">22</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">7.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Regulatory Responsibility</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">22</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">7.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Right of Reference</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">23</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">7.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Regulatory Support</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">23</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 8 Manufacturing</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">24</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">8.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Metagenomi Manufacturing Responsibilities</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">24<br>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">8.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Development Supply Agreement</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">24</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">8.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Commercial Supply Agreement</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">25</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">8.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Ionis&#8217; Assumption of Manufacturing Responsibilities</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">25</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">8.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Manufacturing After the Metagenomi Supply Term</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">25</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 9 Consideration; Financial Terms</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">25</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Upfront Payment</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">25</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>[***]</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">26</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Option Exercise Fee.</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">26</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Ionis Product Milestone Payments</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">26</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Ionis Products for [***] Target Populations</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">29</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Ionis Product Royalty Payments</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">29</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.7.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Existing In-License Agreements</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">31</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.8.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>New In-License Agreements</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">32</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.9.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Payment Obligations Under Certain In-License Agreements</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">33</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.10.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Metagenomi Product Economics</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">33</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.11.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Other Payments</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">35</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.12.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Right to Offset</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">35</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.13.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Records and Audits</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">35</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.14.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Currency of Payment; Non-Refundable Payments</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">36</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.15.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Late Fees</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">36</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">9.16.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Currency Restrictions</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">37</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">9.17.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Withholding Taxes</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">37</td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 10 Intellectual Property</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">37</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Ownership of Inventions</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">37</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">10.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Patent Prosecution</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">38</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Patent Enforcement</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">40</td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">ii</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" id="z76c37c21dc264e83aa8da25f2a88b303" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">10.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Defense of Claims Brought by Third Parties</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); font-weight: normal; text-align: right;">41</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Patent Listing</div>
            </td>
            <td style="width: 5%; vertical-align: top; font-weight: normal; text-align: right;">41</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">10.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Common Ownership Legislation</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">42</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.7.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Patent Term Extension</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">42</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">10.8.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Recording</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">42</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.9.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Unitary Patent System</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">42</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">10.10.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Trademarks</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">42</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">10.11.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Common Interest</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">43</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 11 Confidentiality</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">43</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">11.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Confidential Information</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">43</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">11.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>No Use of Name</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">45</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">11.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Residual Knowledge</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">45</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">11.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Public Announcements and Subsequent Disclosures</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">46</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">11.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Publications</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">46</td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 12 Representations, Warranties, and Covenants</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">47</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">12.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Mutual Representations and Warranties</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">47</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">12.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Additional Representations of Metagenomi</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">12.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Covenants of Metagenomi</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">49</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">12.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Additional Representations of Ionis</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">50</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">12.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Covenants of Ionis</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">51</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">12.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Warranty Disclaimer</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">52</div>
            </td>
          </tr>
          <tr>
            <td style="vertical-align: top;" colspan="2">
              <div>Article 13 Indemnification; Limitation of Liability; Insurance</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">52</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">13.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Indemnification of Metagenomi by Ionis</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">52</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">13.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Indemnification of Ionis by Metagenomi</div>
            </td>
            <td style="width: 5%; vertical-align: top;">
              <div style="text-align: right;">53</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">13.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Losses for the Co-Co Products</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">53</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">13.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Conditions to Indemnification</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">54</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">13.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Limited Liability</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">54</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">13.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Insurance Obligations</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">54</td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 14 Term and Termination</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">55</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">14.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Term</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">55</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">14.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Termination</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">55</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">14.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Effects of Termination</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">56</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">14.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Confidential Information</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">59</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">14.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Surviving Provisions</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">59</td>
          </tr>
          <tr>
            <td style="vertical-align: top; background-color: rgb(204, 238, 255);" colspan="2">
              <div>Article 15 Miscellaneous</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">60</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.1.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Dispute Resolution</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">60</td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">iii</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" border="0" id="z604ee3241ac34f59803bffe38a7f1dad" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.2.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Designation of Affiliates</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">62</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.3.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Patent Disputes</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">62</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.4.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Injunctive Relief</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.5.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Governing Law</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.6.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Cumulative Remedies</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.7.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Notices</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">63</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.8.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Amendment; Waiver</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="text-align: right;">64</div>
            </td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.9.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Assignment and Successors</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">64</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.10.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Rights in Bankruptcy</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">64</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.11.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Force Majeure</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">65</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.12.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Interpretation</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">66</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.13.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Integration</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">66</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.14.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Severability</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">66</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.15.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Further Assurances</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">67</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div style="margin-left: 9pt;">15.16.</div>
            </td>
            <td style="width: 87%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>Counterparts</div>
            </td>
            <td style="width: 5%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">67</td>
          </tr>
          <tr>
            <td style="width: 8%; vertical-align: top;">
              <div style="margin-left: 9pt;">15.17.</div>
            </td>
            <td style="width: 87%; vertical-align: top;">
              <div>Relationship of the Parties</div>
            </td>
            <td style="width: 5%; vertical-align: top; text-align: right;">67</td>
          </tr>

      </table>
      <div>&#160;</div>
      <div><font style="font-weight: bold;"><u>Schedules</u></font>:</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" border="0" id="zcbcbc06e1d8d44df9e727da3e7a6f961" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div><u>Schedule1.114</u></div>
            </td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);">
              <div>[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top;">
              <div><u>Schedule1.146</u></div>
            </td>
            <td style="width: 80%; vertical-align: top;">
              <div>Licensed Patent Rights&#160;</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1"><u>Schedule 1.166</u></td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">[***]</td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top;">
              <div><u>Schedule 1.175</u></div>
            </td>
            <td style="width: 80%; vertical-align: top;">
              <div>Metagenomi Platform Patent Rights <br>
              </div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1"><u>Schedule 2.1.1(a)</u></td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">[***]</td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top;">
              <div><u>Schedule 2.2</u></div>
            </td>
            <td style="width: 80%; vertical-align: top;">
              <div>[***] Drug Discovery Plan</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1"><u>Schedule 2.3.1</u></td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">Exploratory Research Plan</td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top;">
              <div><u>Schedule 8.2</u></div>
            </td>
            <td style="width: 80%; vertical-align: top;">
              <div>Development Supply Agreement Key Terms&#160;</div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1"><u>Schedule 11.4</u></td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">Press Release(s)</td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top;">
              <div><u>Schedule 12.2</u></div>
            </td>
            <td style="width: 80%; vertical-align: top;">
              <div>Metagenomi Disclosure Schedule&#160;<u></u></div>
            </td>
          </tr>
          <tr>
            <td style="width: 20%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1"><u>Schedule 12.4</u></td>
            <td style="width: 80%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">Ionis Disclosure Schedule</td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">iv</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <!--PROfilePageNumberReset%Num%1%%%-->
      <div style="text-align: center; margin-right: 114.3pt; margin-left: 123.2pt; font-weight: bold;">COLLABORATION AND LICENSE AGREEMENT</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 54pt;">This <font style="font-weight: bold;">COLLABORATION AND LICENSE AGREEMENT </font>(this &#8220;<font style="font-weight: bold;">Agreement</font>&#8221;) is entered into as of November 10, 2022 (the &#8220;<font style="font-weight: bold;">Effective Date</font>&#8221;), by and between Ionis Pharmaceuticals, Inc., a Delaware corporation, having its principal place of business at 2855 Gazelle Court, Carlsbad, CA 92010 (&#8220;<font style="font-weight: bold;">Ionis</font>&#8221;),



        and Metagenomi, Inc., a Delaware corporation, having its principal place of business at 1545 Park Avenue, Emeryville, CA 94608 (&#8220;<font style="font-weight: bold;">Metagenomi</font>&#8221;). Metagenomi and Ionis are sometimes referred to herein
        individually as a &#8220;<font style="font-weight: bold;">Party</font>&#8221; and collectively as the &#8220;<font style="font-weight: bold;">Parties</font>.&#8221;</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 54pt;">WHEREAS, Metagenomi is a biopharmaceutical company that controls certain patent rights, know-how, technology, and expertise with respect to gene editing;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 54pt;">WHEREAS, Ionis is a biopharmaceutical company focused on developing and commercializing pharmaceutical and biopharmaceutical products;</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 54pt;">WHEREAS, Metagenomi and Ionis desire to enter into a collaboration to utilize Metagenomi&#8217;s and Ionis&#8217; expertise and each Party&#8217;s platform to perform research services and other activities focused
        on the (a) discovery and development of therapeutics, and (b) advancing certain gene editing technologies to enable improved performance, novel mechanisms, and novel delivery strategies; and</div>
      <div><br>
      </div>
      <div style="text-align: justify; text-indent: 54pt;">WHEREAS, Metagenomi desires to grant to Ionis, and Ionis desires to receive from Metagenomi, an exclusive license under the Licensed Technology to Exploit Licensed Systems and Licensed Products
        under the terms and conditions set forth herein.</div>
      <div><br>
      </div>
      <div style="text-indent: 54pt;">NOW, THEREFORE, the Parties agree as follows:</div>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_TOC_250041"></a>Article 1<a name="z_bookmark0"></a></div>
      <div style="text-align: center; font-weight: bold;">Overview</div>
      <div>&#160;</div>
      <div style="text-align: justify; text-indent: 54pt;">The Parties intend to undertake a strategic research collaboration under this Agreement, consisting of drug discovery and exploratory research activities to advance new medicines using gene editing
        strategies, with the goal of discovering novel medicines for Ionis to Develop and Commercialize on its own or to co-Develop and co-Commercialize with Metagenomi.</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zfa4ccb23a0d84285a91beb1a59d0bd1c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt; vertical-align: top;"><a name="z1.1._Drug_Discovery_Program._The_Parties"></a><font style="font-weight: bold;">1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Drug Discovery Program</font>. The Parties intend that, under this Agreement, the Parties will seek to discover therapeutic products directed to specific genetic targets
                selected by Ionis under a Drug Discovery Program and pursuant to a Drug Discovery Plan for each specific genetic target, as permitted by this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z886e930686b24818a385be1cd6be680f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt; vertical-align: top;"><a name="z1.2._Development_and_Commercialization._"></a><font style="font-weight: bold;">1.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Development and Commercialization</font>. For each Drug Discovery Program, once the Parties identify a candidate that is suitable for Development, as between the Parties,
                Ionis will be responsible for Development and Commercialization of products resulting from such Drug Discovery Program either on its own or, if Metagenomi exercises its option, together with Metagenomi.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb353ec7bc2214b2691a6308743bd07b4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z1.3._Co-Development_and_Co-Commercializa"></a><font style="font-weight: bold;">1.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Co-Development and Co-Commercialization</font>. Metagenomi will have an exclusive option to co- Develop and co-Commercialize products with Ionis under a limited number of Drug
                Discovery Programs. For any such option exercised by Metagenomi, the Parties will enter into a separate Co- Development and Co-Commercialization Agreement, as set forth herein. Metagenomi will have a right to opt-out of such co-Development
                and co-Commercialization at specific times, as set forth herein.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">1</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za3719c9e00e446828472124c434c3ec3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z1.4._Exploratory_Research._The_Parties_w"></a><font style="font-weight: bold;">1.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exploratory Research</font>. The Parties will also conduct an Exploratory Research Program under this Agreement. The Parties intend that, under the Exploratory Research
                Program, the Parties will conduct collaborative research pursuant to an Exploratory Research Plan to jointly [***] and such other activities as agreed upon by the Joint Research Committee in accordance with this Agreement. Any such
                improvements resulting from the Parties&#8217; exploratory research under this Agreement will be incorporated into the Parties&#8217; drug discovery collaboration.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1c09201ca71141b9ad4b67e40535e15a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z1.5._Governance._The_Parties_have_agreed"></a><font style="font-weight: bold;">1.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Governance</font>. The Parties have agreed to form (a) a Joint Steering Committee to coordinate, oversee, and monitor the Parties&#8217; activities under this Agreement; and (b) a
                Joint Research Committee reporting to the JSC to coordinate, oversee, and monitor the Parties&#8217; research and drug discovery activities under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb4be6bbcb37c4bfbb44a5f29a2207483" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z1.6._Purpose._The_purpose_of_this_Articl"></a><font style="font-weight: bold;">1.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Purpose</font>. The purpose of this <u>Article 1</u> (Overview) is to provide a high-level overview of the roles, responsibilities, rights, and obligations of each Party
                under this Agreement, and therefore this <u>Article 1</u> (Overview) is qualified in its entirety by the more detailed provisions of this Agreement set forth below.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="z_TOC_250040"></a>Article 2 </div>
      <div style="text-align: center; font-weight: bold;">Collaboration</div>
      <div style="text-align: center;">&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z08b488c31cb541f7b27ee836ecfe173f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark1"></a><a name="z_TOC_250039"></a><font style="font-weight: bold;">2.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Selection of Collaboration Targets</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9db6d82eab8349588ecfcd99493c3c83" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;">&#160;</td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.1.1._Wave_1_Targets."></a><a name="z_bookmark2"></a><font style="font-weight: bold;">2.1.1.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Wave 1 Targets</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zda551287bef8470da4696523fad320e0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;">&#160;</td>
            <td style="vertical-align: top; width: 36pt;"><a name="za_Initial_Wave_1_Target._The_first_Col"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Initial Wave 1 Target</font>. The first Collaboration Target will be [***], as set forth on <u>Schedule 2.1.1(a)</u> ([***]) (&#8220;[***]&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z99234d9e665841af96129ec70a8881a9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Second_Wave_1_Target._Within_30_days"></a><a name="z_bookmark3"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Second Wave 1 Target</font>. Within [***] of the Effective Date, the Parties will mutually agree on the second gene target as a Collaboration Target (the &#8220;<font style="font-weight: bold;">Second Wave 1 Target</font>&#8221;). The Second Wave 1 Target will be a target for which a Licensed Product would be delivered only to [***]. If the Parties do not agree on a Second Wave 1 Target within such [***]
                period, then the Parties will mutually agree on an additional period to determine a second gene target to be the Second Wave 1 Target.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z89f4bb144f444b9da3d4c2808c6f976f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Additional_Wave_1_Target_Selection._"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Wave 1 Target Selection</font>. At any time during the period commencing on the Effective Date and ending on the date that is [***] following the Effective Date (&#8220;<font style="font-weight: bold;">Additional Wave 1 Target Selection Period</font>&#8221;), Ionis may, in its sole discretion, but subject to <u>Section 2.1.4</u> (Encumbrance Check), select up to two additional gene targets as proposed Collaboration
                Targets by providing written notice to Metagenomi (each such notice, the &#8220;<font style="font-weight: bold;">Additional Wave 1 Target Notice</font>&#8221;), which notice will identify the proposed target (&#8220;<font style="font-weight: bold;">Additional
                  Wave 1 Target</font>&#8221;). The Additional Wave 1 Targets will be targets for which a Licensed Product would be delivered only to [***] or only to [***]; <font style="font-style: italic;">provided </font>that [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z1f6f674df09c48b9bc686fb31ec15acb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.1.2._Wave_2_Target_Options._If_at_any"></a><font style="font-weight: bold;">2.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Wave 2 Target Options</font>. If, at any time during the Drug Discovery Term, (a) [***] or (b) the Parties achieve [***] under the Exploratory Research Activities (the &#8220;<font style="font-weight: bold;">Wave 2 Target Selection Period</font>&#8221;), then Ionis may, in its sole discretion, but subject to <u>Section 2.1.4</u> (Encumbrance Check), select up to four additional gene targets as proposed Collaboration
                Targets by providing written notice to Metagenomi (each such notice, a &#8220;<font style="font-weight: bold;">Wave 2 Target Notice</font>&#8221;), which notice will identify the proposed target (&#8220;<font style="font-weight: bold;">Wave 2 Target</font>&#8221;).


                Each Wave 2 Target will be a target for which a Licensed Product would be delivered only to [***] or only to [***], or [***] that has, at the time of the Wave 2 Target Notice for such Wave 2 Target [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdac289fe9b594418ae26621dac85f1a0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.1.3._Target_Substitutions._On_a_Drug_D"></a><a name="z_bookmark4"></a><font style="font-weight: bold;">2.1.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Target Substitutions</font>. On a Drug Discovery Program-by-Drug Discovery Program basis, Ionis will have the right to substitute the Collaboration Target for a Drug Discovery Program in accordance with
                this <u>Section 2.1.3</u> (Target Substitutions).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd5323a77ed754856bfaacd9d74c44ab4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Discretionary_Substitutions._At_any_"></a><a name="z_bookmark5"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Discretionary Substitutions</font>. At any time before [***] (the &#8220;<font style="font-weight: bold;">Target Substitution Period</font>&#8221;), Ionis may, in its sole discretion, but
                subject to <u>Section 2.1.4</u> (Encumbrance Check), replace the Collaboration Target for such Drug Discovery Program by providing written notice to Metagenomi, which notice will identify the proposed replacement gene target. Ionis may
                substitute (i) up to [***] and (ii) up to [***], in each case ((i) and (ii)), for any reason. Any Collaboration Target that is substituted out pursuant to this <u>Section 2.1.3(a)</u> (Discretionary Substitutions) will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4ecd9475fb0549c08cb9def4f2d59cbb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Substitutions_for_Technological_Infe"></a><a name="z_bookmark6"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Substitutions for Technological Infeasibility</font>. If the JSC determines that it is technologically infeasible to Develop a Development Candidate for a Collaboration Target
                (&#8220;<font style="font-weight: bold;">Technological Infeasibility</font>&#8221;), then Ionis may, in its sole discretion, but subject to <u>Section 2.1.4</u> (Encumbrance Check), substitute such Collaboration Target by providing written notice to
                Metagenomi, which notice will identify the proposed replacement gene target. [***] and any substitutions that are for Technological Infeasibility will [***]. Any Collaboration Target that is substituted out pursuant to this <u>Section
                  2.1.3(b)</u> (Substitutions for Technological Infeasibility) will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc44137cf71f947bf98e9ab2074f6874e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Substitution_After_Resolution_of_Tec"></a><a name="z_bookmark7"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Substitution After Resolution of Technological Infeasibility</font>. If a Collaboration Target is substituted out for Technological Infeasibility pursuant to <u>Section</u>&#160;<u>2.1.3(b)</u>
                (Substitutions for Technological Infeasibility) and, [***], then Metagenomi will notify Ionis, which notice will include [***]. Subject to clauses (i) and (ii) of <u>Section 2.1.4(a)</u>&#160; (Encumbered Targets), Ionis will have the right to
                substitute a current Collaboration Target for such previous Collaboration Target by providing written notice to Metagenomi within [***] of receipt of notice from Metagenomi that [***]. [***] and any substitutions that are as a result of
                resolution of a Technological Infeasibility will [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zba6db1e2dafa43058260289f6de314bc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zd_Substitution_Procedure._Any_written_"></a>(d)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Substitution Procedure</font>. Any written notice provided by Ionis to Metagenomi pursuant to <u>Section 2.1.3(a)</u> (Discretionary Substitutions), <u>Section 2.1.3(b)</u>
                (Substitutions for Technological Infeasibility), or <u>Section 2.1.3(c)</u> (Substitutions After Resolution of Technological Infeasibility) will be a &#8220;<font style="font-weight: bold;">Replacement Target Notice</font>&#8221; and the proposed
                replacement gene target identified in any Replacement Target Notice will be a &#8220;<font style="font-weight: bold;">Proposed Replacement Target</font>&#8221;. Each Replacement Target Notice will specify which current Collaboration Target should be
                removed as a result of such replacement, and, unless otherwise agreed by the Parties, each Proposed Replacement Target will [***]. Promptly after such Proposed Replacement Target becomes a Collaboration Target pursuant to <u>Section
                  2.1.4(c)</u> (Effects if a Proposed Target is Available), Metagenomi will [***] after such Proposed Replacement Target becomes a Collaboration Target pursuant to <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z4235210614eb40eda05432a0635ee9d2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;">&#160;</td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.1.4._Encumbrance_Check."></a><a name="z_bookmark8"></a><font style="font-weight: bold;">2.1.4.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Encumbrance Check</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za454ab96cc8e44b291efdc79400eb371" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Encumbered_Targets._Metagenomi_will_"></a><a name="z_bookmark9"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Encumbered Targets</font>. Metagenomi will notify Ionis within [***] after Metagenomi&#8217;s receipt of an Additional Wave 1 Target Notice, a Wave 2 Target Notice, or a Replacement
                Target Notice if, at the time of receipt of such notice, (i) Metagenomi is [***], (ii) Metagenomi is [***], or (iii) the Proposed Target is [***], pursuant to which Metagenomi has [***] (each of (i) through (iii), a &#8220;<font style="font-weight: bold;">Pre-Existing Restriction</font>&#8221; and such Proposed Target, an &#8220;<font style="font-weight: bold;">Encumbered Target</font>&#8221;). Notwithstanding the foregoing, a Collaboration Target that has been substituted out for
                Technological Infeasibility but for which Ionis later selects as a Proposed Replacement Target pursuant to <u>Section 2.1.3(c)</u> (Substitutions After Resolution of Technological Infeasibility) will only be an Encumbered Target if the
                foregoing clause (i) or clause (ii) applies with respect to such Proposed Replacement Target. If Metagenomi does not notify Ionis within such [***] period that the [***]. If Metagenomi (x) notifies Ionis that a Proposed Target is Available
                or (y) does not provide notice that a Proposed Target is an Encumbered Target within the [***], then, in either case ((x) or (y)), such Proposed Target will be deemed to be Available, at which point <u>Section 2.1.4(c)</u> (Effects if a
                Proposed Target is Available) will apply. If a Proposed Target is an Encumbered Target, then Ionis may select another Proposed Target (and another if such other Proposed Target is an Encumbered Target and so on) until such time that Ionis
                selects a Proposed Target that is Available, at which point <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available) will apply.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1c2e62deb871415a8995ce3c9731c0fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Expiration_of_Pre-Existing_Restricti"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Expiration of Pre-Existing Restrictions</font>. On [***], Ionis will [***], to facilitate its activities pursuant to <u>Section 4.1.5(b)</u> (Specific Responsibilities of the
                JSC), [***]. If at any time during the Additional Wave 1 Target Selection Period, the Wave 2 Target Selection Period, or the Target Substitution Period, as applicable, any Pre-Existing Restriction that precluded Ionis from selecting a
                Proposed Target as a Collaboration Target later expires, terminates, or is otherwise modified such that such Proposed Target would no longer be an Encumbered Target, and at such time (i) Ionis has not [***] as permitted under this
                Agreement, or (ii) Ionis has designated all Collaboration Targets as permitted under this Agreement, but Ionis has not exhausted its right to substitute existing Collaboration Targets as permitted under <u>Section 2.1.3(a)</u>
                (Discretionary Substitutions), <u>Section 2.1.3(b)</u> (Substitutions for Technological Infeasibility), or <u>Section 2.1.3(c)</u> (Substitution After Resolution of Technological Infeasibility) (such time period prior to the occurrence of
                both (i) and (ii), the &#8220;<font style="font-weight: bold;">Target Selection and Substitution Period</font>&#8221;), then Metagenomi will notify Ionis of such expiration, termination, or modification unless Ionis has notified the JSC that it is no
                longer interested in pursuing that Encumbered Target as a Collaboration Target.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">4</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z2f52ad7153384baba20a18e0753fcb95" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Effects_if_a_Proposed_Target_is_Avai"></a><a name="z_bookmark10"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Effects if a Proposed Target is Available</font>. If Ionis confirms in writing to Metagenomi that a Proposed Target should be deemed to be a &#8220;Collaboration Target&#8221; under this
                Agreement within [***] of a Proposed Target being deemed Available pursuant to <u>Section 2.1.4(a)</u> (Encumbered Targets), then (i) such Proposed Target will be deemed a &#8220;Collaboration Target&#8221; as of the date of such notice, (ii) the
                Parties, through the JRC, will develop a Drug Discovery Plan for such Collaboration Target in accordance with <u>Section 2.2.2</u> (Additional Drug Discovery Plans), (iii) if the Proposed Target was [***] in accordance with <u>Section 9.2</u>
                ([***]) and, if applicable, the Drug Discovery Term will be extended pursuant to <u>Section 2.2.7</u> (Drug Discovery Term), and (iv) if the Proposed Target was a Proposed Replacement Target, then the Collaboration Target that was
                substituted out will no longer be a &#8220;Collaboration Target&#8221;. If Ionis does not respond within [***] of a Proposed Target being deemed Available pursuant to <u>Section 2.1.4(a)</u> (Encumbered Targets), then such Proposed Target will not be
                deemed a &#8220;Collaboration Target&#8221;.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6887932f6ca6492784940e6ff35a9e0a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250038"></a><font style="font-weight: bold;">2.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Drug Discovery Program</font><a name="z_bookmark11"></a>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z93d64b2416d241a6b1f9587a078bfa43" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.1._Initial_Drug_Discovery_Plan._The_"></a><font style="font-weight: bold;">2.2.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Initial Drug Discovery Plan</font>. The principal Development objectives for each Drug Discovery Program will be set forth in a written plan that includes: (a) the specific
                activities to be performed by each Party through selection of a Development Candidate for such Drug Discovery Program, including the Gene Editing modality within the Field for such Development Candidate, (b) the estimated timelines for the
                performance of such activities, and (c) the Development Candidate selection criteria (each such plan, as may be updated from time to time, a &#8220;<font style="font-weight: bold;">Drug Discovery Plan</font>&#8221; and the activities to be performed by
                the Parties thereunder, the &#8220;<font style="font-weight: bold;">Drug Discovery Activities</font>&#8221;). In addition, each Drug Discovery Plan will include a written budget pursuant to which Metagenomi will perform the Drug Discovery Activities
                allocated to Metagenomi under such Drug Discovery Plan, which budget will include (i) [***], and (ii) [***] (each such budget, a &#8220;<font style="font-weight: bold;">Drug Discovery Budget</font>&#8221;). The initial Drug Discovery Plan agreed to by
                the Parties for [***] is attached hereto as <u>Schedule 2.2</u> ([***] Drug Discovery Plan).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z37a1fc345afb4305a73af15852f00bee" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.2._Additional_Drug_Discovery_Plans._"></a><a name="z_bookmark12"></a><font style="font-weight: bold;">2.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Drug Discovery Plans</font>. No later than [***] after (a) the Parties agree on the Second Wave 1 Target pursuant to <u>Section 2.1.1(b)</u> (Second Wave 1 Target)
                or (b) a Proposed Target is deemed a Collaboration Target under this Agreement pursuant to <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available), which period shall be appropriately extended for the Parties to undertake the
                process described in <u>Section 2.2.4</u> ([***] for Additional Drug Discovery Plans), if applicable, in each case, the Parties will develop, through the JRC, a Drug Discovery Plan for such Collaboration Target (an &#8220;<font style="font-weight: bold;">Additional Drug Discovery Plan</font>&#8221;) in accordance with this <u>Section 2.2.2</u> (Additional Drug Discovery Plans). The JRC will submit each proposed Additional Drug Discovery Plan to the JSC for the JSC to
                review, discuss, and determine whether to approve. Unless otherwise agreed by the Parties, the content of each Additional Drug Discovery Plan will be consistent in scale and scope to that set forth in the Drug Discovery Plan for [***]
                attached hereto as <u>Schedule 2.2</u> ([***] Drug Discovery Plan).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6a258affedeb4946b6b95f6d4d98fdbf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.3._Amendments_to_the_Drug_Discovery_"></a><a name="z_bookmark13"></a><font style="font-weight: bold;">2.2.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Amendments to the Drug Discovery Plans</font>. At least [***] during the Drug Discovery Term, or upon either Party&#8217;s request, the JRC will develop and propose updates to each
                Drug Discovery Plan; <font style="font-style: italic;">provided </font>that [***]. Any proposed updates to a Drug Discovery Plan will be submitted to the JSC for approval. The JSC will review, discuss, and determine whether to approve any
                such proposed update to a Drug Discovery Plan. Each such update to a Drug Discovery Plan will become effective and will supersede the previous Drug Discovery Plan for the applicable Drug Discovery Program upon approval thereof by the JSC.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">5</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z23ad2879b6cb48acb3a4f0c804e02a5f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.4._Gene_Editing_Modality_for_Additio"></a><a name="z_bookmark14"></a><font style="font-weight: bold;">2.2.4.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">[***] for Additional Drug Discovery Plans</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2564b89ed6f44ed19378209f66cb83ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_New_Gene_Editing_Modalities._At_each"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">New </font>[***]. At each JSC meeting during the Target Selection and Substitution Period, Metagenomi will [***]. In addition, [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zac2dc20d3c234925a195ac920aec2d81" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Selection_of_Gene_Editing_Modalities"></a><a name="z_bookmark15"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Selection of </font>[***]. The JSC will discuss and determine [***] under this Agreement pursuant to <u>Section</u>&#160;<u>2.1.4(c)</u> (Effects if a Proposed Target is
                Available) from the [***] will be set forth in the applicable Additional Drug Discovery Plan determined pursuant to <u>Section 2.2.2</u> (Additional Drug Discovery Plans). For clarity, if the JSC [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z19192a443c734e1aa243034328499328" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Incremental_Development_Costs._If_i"></a><a name="z_bookmark16"></a>(c)</td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Incremental Development Costs</font>. If, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8203a732f6804bc5ac53ec192c258e39" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.5._Development_of_Multiple_Modalitie"></a><a name="z_bookmark17"></a><font style="font-weight: bold;">2.2.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Development of </font>[***]<font style="font-weight: bold;"> for a Drug Discovery Program</font>. If either Party wishes to Develop a Licensed Product comprising a [***] that
                is not already set forth in the Drug Discovery Plan for such Drug Discovery Program, then such Party may propose such additional activities to the other Party and the Parties will discuss whether to amend such Drug Discovery Plan or create
                a separate Drug Discovery Program for such [***]. If the Parties agree to include the additional [***] in the Drug Discovery Program, then the Parties will enter into a mutually acceptable amended Drug Discovery Plan that includes the
                additional [***]. For clarity, neither Party will have any obligation to agree to amend a Drug Discovery Plan to include any additional [***] that were not set forth in the initial Drug Discovery Plan for the applicable Drug Discovery
                Program.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z5922f7ba7c504d86a89cb6275a0687d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.6._Delivery_of_Development_Candidate"></a><a name="z_bookmark18"></a><font style="font-weight: bold;">2.2.6.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Delivery of Development Candidate; Development Candidate Report</font>. The objective of each Drug Discovery Plan will be to identify both a lead and a backup candidate for
                development that each meet the development candidate criteria set forth in such Drug Discovery Plan. No later than [***] after completion by the Parties of all Drug Discovery Activities set forth under the applicable Drug Discovery Plan
                with respect to each Collaboration Target, or such earlier time mutually agreed upon by the Parties, each Party will deliver to the JSC a report summarizing all results, information, and data that were generated in connection with the
                performance of the Drug Discovery Activities under such Drug Discovery Plan, including information regarding any therapeutic agents that meet the development candidate criteria (each, a &#8220;<font style="font-weight: bold;">Development
                  Candidate Report</font>&#8221;). Following receipt of the Development Candidate Reports, and at such earlier times that the Parties have exchanged data and results regarding any therapeutic agent that meets the development candidate criteria
                set forth in the applicable Drug Discovery Plan, the JSC will review and discuss such Development Candidate Reports and other data and results, and Ionis may, in its sole discretion, elect to designate one or more such therapeutic agents as
                Development Candidates hereunder (regardless of whether any such therapeutic agents meet the development candidate criteria).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3b3e51b8f7f94668a04a9079a7fba5f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.2.7._Drug_Discovery_Term._On_a_Drug_Di"></a><a name="z_bookmark19"></a><font style="font-weight: bold;">2.2.7.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Drug Discovery Term</font>. On a Drug Discovery Program-by-Drug Discovery Program basis, the Drug Discovery Activities for a Drug Discovery Program will be performed by or on
                behalf of the Parties during the period commencing on the selection of a Collaboration Target for such Drug Discovery Program and, unless this Agreement is earlier terminated with respect to such Collaboration Target, expiring upon the
                earlier of (a) completion of all Drug Discovery Activities set forth in the Drug Discovery Plan for such Drug Discovery Program and presentation to the JSC of such Drug Discovery Activities, (b) the [***] anniversary of the Effective Date,
                and (c) selection of a Development Candidate for such Drug Discovery Program (the &#8220;<font style="font-weight: bold;">Drug Discovery Term</font>&#8221;); <font style="font-style: italic;">provided </font>that [***], the [***] anniversary of the
                Effective Date.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">6</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z8d806e048780490ebb536127c6068fcf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250037"></a><font style="font-weight: bold;">2.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Exploratory Research Program</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdffaab082b71431a9f5c04fa8cfff54a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.3.1._Exploratory_Research_Plan._The_pr"></a><a name="z_bookmark20"></a><font style="font-weight: bold;">2.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exploratory Research Plan</font>. The [***], and any other Development activities that the JRC agrees to include pursuant to any amendment under <u>Section 2.3.2</u>
                (Amendments to the Exploratory Research Plan) (the &#8220;<font style="font-weight: bold;">Exploratory Research Program</font>&#8221;) will be set forth in a written plan that includes: (a) the specific activities to be performed by each Party and (b)
                the estimated timelines for the performance of such activities (such plan, as may be updated from time to time, the &#8220;<font style="font-weight: bold;">Exploratory Research Plan</font>&#8221; and the activities to be performed by the Parties
                thereunder, the &#8220;<font style="font-weight: bold;">Exploratory Research Activities</font>&#8221;). In addition, the Exploratory Research Plan will include a written budget pursuant to which Metagenomi will perform the Exploratory Research
                Activities allocated to Metagenomi under such Exploratory Research Plan, which budget will include (i) [***], and (ii) [***] (the &#8220;<font style="font-weight: bold;">Exploratory Research Budget</font>&#8221;). The initial Exploratory Research Plan
                is set forth on <u>Schedule 2.3.1</u> (Exploratory Research Plan).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdccdb4b6b15d47deb415f71505c3fff9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.3.2._Amendments_to_the_Exploratory_Res"></a><a name="z_bookmark21"></a><font style="font-weight: bold;">2.3.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Amendments to the Exploratory Research Plan</font>. At least annually during the Exploratory Research Term no later than [***] of each Calendar Year, or upon either Party&#8217;s
                request, the JRC will develop and propose updates to the Exploratory Research Plan or Exploratory Research Budget for the next fiscal year, or such other period as the Parties may mutually agree, and will submit any such proposed change to
                the JSC. Additionally, at any time during the Exploratory Research Term, the JRC may develop and propose <font style="font-style: italic;">ad hoc </font>updates to the Exploratory Research Plan or Exploratory Research Budget based on the
                then-current results and data. The JSC will review, discuss, and determine whether to approve any such proposed change to the Exploratory Research Plan or Exploratory Research Budget. Each such update to the Exploratory Research Plan or
                Exploratory Research Budget will become effective and will supersede the previous Exploratory Research Plan or Exploratory Research Budget upon approval thereof by the JSC.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8e47bf3325de4eaea36341907135ca3d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.3.3._Exploratory_Research_Term._The_Ex"></a><font style="font-weight: bold;">2.3.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exploratory Research Term</font>. The Exploratory Research Activities will be performed by or on behalf of the Parties during the period commencing on the Effective Date and,
                unless this Agreement is earlier terminated with respect to the Exploratory Research Program, expiring upon the earlier of (a) [***], and (b) the [***] anniversary of the Effective Date (the &#8220;<font style="font-weight: bold;">Exploratory
                  Research Term</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">7</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zbf2fc398fcff4000b194727caa208565" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z2.4._Conduct_of_Collaboration_Activities"></a><font style="font-weight: bold;">2.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Conduct of Collaboration Activities</font>. Each Party, directly or through its Affiliates or, subject to <u>Section 3.3</u> (Subcontractors), Subcontractors, will use
                Commercially Reasonable Efforts to conduct the Drug Discovery Activities and Exploratory Research Activities (collectively, the &#8220;<font style="font-weight: bold;">Collaboration Activities</font>&#8221;) assigned to it under the applicable Drug
                Discovery Plan or Exploratory Research Plan (collectively, the &#8220;<font style="font-weight: bold;">Collaboration Program Plans</font>&#8221;) and in a professional and timely manner. Each Party will, and will require its Affiliates and
                Subcontractors to, perform its obligations under the Collaboration Program Plans in compliance with Applicable Law.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z110c1efc8bf243f19ef04f4a2e16ba45" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250036"></a><font style="font-weight: bold;">2.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Cost of Collaboration Activities</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0d0a6872343d448195d3ad56ba574a3a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.5.1._Reimbursement_by_Ionis._Ionis_wil"></a><a name="z_bookmark22"></a><font style="font-weight: bold;">2.5.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Reimbursement by Ionis</font>. Ionis will reimburse Metagenomi for all (a) [***] and (b) [***], in each case ((a) and (b)), actually incurred by Metagenomi in the performance
                of the Exploratory Research Activities during the Exploratory Research Term to the extent in compliance with both the Exploratory Research Plan and the amounts budgeted therefor in the Exploratory Research Budget [***] (such amount, the &#8220;<font style="font-weight: bold;">Metagenomi Exploratory Research Costs</font>&#8221;) up to $[***] in the aggregate (the &#8220;<font style="font-weight: bold;">Reimbursement Cap</font>&#8221;). If the aggregated Metagenomi Exploratory Research Costs during the
                Exploratory Research Term are <font style="font-style: italic;">less </font>than the Reimbursement Cap, then Ionis will also reimburse Metagenomi for all (1) [***] and (2) [***], in each case ((1) and (2)), actually incurred by Metagenomi
                in the performance of the Drug Discovery Activities during the Exploratory Research Term to the extent in compliance with both the applicable Drug Discovery Plans and the amounts budgeted therefor in the applicable Drug Discovery Budgets
                [***] (&#8220;<font style="font-weight: bold;">Metagenomi Drug Discovery Costs</font>&#8221;) up to [***]. In each Calendar Quarter during the Exploratory Research Term, unless and until Ionis&#8217; aggregated payments under this <u>Section 2.5.1</u>
                (Reimbursement by Ionis) reach the Reimbursement Cap, Ionis will pay Metagenomi $[***] to cover the Metagenomi Exploratory Research Costs and, if applicable, the Metagenomi Drug Discovery Costs for such Calendar Quarter (such amount, the &#8220;<font style="font-weight: bold;">Quarterly Reimbursement Payments</font>&#8221;), within [***] following receipt of an invoice from Metagenomi therefor. No later than [***] following the conclusion of each [***] during the Exploratory Research Term,
                Metagenomi will provide to Ionis a written report of all Metagenomi Exploratory Research Costs and Metagenomi Drug Discovery Costs incurred by or on behalf of Metagenomi during the applicable [***] (such reports, the &#8220;<font style="font-weight: bold;">Metagenomi Collaboration Cost Reports</font>&#8221;). If the amount set forth in the Metagenomi Collaboration Cost Report for a [***] $[***], then no further action is required by the Parties, except that [***]. If
                the amount set forth in the Metagenomi Collaboration Cost Report for a [***], then [***] under this <u>Section 2.5.1</u> (Reimbursement by Ionis). For clarity, Ionis will have the right to [***].</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify; margin-right: 5.7pt; margin-left: 86.95pt;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z2ae0cad56dbd4ecc910facd6488c8f63" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.5.2._Cost_of_Other_Collaboration_Activ"></a><font style="font-weight: bold;">2.5.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Cost of Other Collaboration Activities</font>. Except with respect to amounts reimbursed by Ionis pursuant to <u>Section 2.5.1</u> (Reimbursement by Ionis), Metagenomi will
                be responsible for all costs and expenses incurred by or on behalf of Metagenomi in the performance of the Collaboration Activities allocated to Metagenomi in the applicable Collaboration Program Plans, including in the performance of all
                Drug Discovery Activities after the expiration of the Exploratory Research Term. In addition, Ionis will be responsible for all costs and expenses incurred by or on behalf of Ionis in the performance of the Collaboration Activities
                allocated to Ionis in the applicable Collaboration Program Plans.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">8</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf9aeffa6a2b14f5b8cbace779acc9796" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250035"></a><font style="font-weight: bold;">2.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Collaboration Program Records and Reports</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd90fab8bbe8e4978a277cc8c066be06b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.6.1._Records._Each_Party_will_maintain"></a><font style="font-weight: bold;">2.6.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Records</font>. Each Party will maintain, or cause to be maintained, records of its Collaboration Activities in sufficient detail and in a good scientific manner appropriate
                for scientific, patent, and regulatory purposes, which records will reasonably reflect the work performed by such Party under each Collaboration Program Plan.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z9f5896e45a484033a1bb29760784f11c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.6.2._Collaboration_Program_Reports._Du"></a><a name="z_bookmark23"></a><font style="font-weight: bold;">2.6.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Collaboration Program Reports</font>. During the Collaboration Term, in advance of each meeting of the JSC (unless otherwise agreed by the JSC), each Party will submit to the
                JSC for its review and discussion written materials that include a reasonably detailed summary of the Collaboration Activities performed by or on behalf of such Party during the most recently completed Calendar Quarter, which summary will
                include [***] (each, a &#8220;<font style="font-weight: bold;">Collaboration Program Report</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z3643e71458214e689a2ae4f700b3b45d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark24"></a><a name="z_TOC_250034"></a><font style="font-weight: bold;">2.7.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis Proprietary Toolbox of Chemical Modifications</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcd60f2a6acc64436bb818384de5092f6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.7.1._Option_Grant._If_any_Ionis_Propri"></a><font style="font-weight: bold;">2.7.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Grant</font>. If any Ionis Proprietary Toolbox of Chemical Modifications is necessary or reasonably useful for Metagenomi to practice any Metagenomi Collaboration
                Technology or Joint Collaboration Technology (such Intellectual Property Rights, &#8220;<font style="font-weight: bold;">Ionis Background Technology</font>&#8221;), then Metagenomi will have an option to obtain the license set forth in <u>Section
                  3.2.3(a)</u> (Ionis Background Technology License Grant) to Exploit up to [***] Metagenomi Products in the Field (&#8220;<font style="font-weight: bold;">Ionis IP Option</font>&#8221;). [***]</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za6540fdb4f234bfb866fce01d952d36c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.7.2._Option_Exercise._Metagenomi_may_e"></a><font style="font-weight: bold;">2.7.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Exercise</font>. Metagenomi may exercise an Ionis IP Option by providing written notice to Ionis (&#8220;<font style="font-weight: bold;">Option Exercise Notice</font>&#8221;) at
                any time during the period commencing on [***] and ending on the date that is [***] after the expiration of the [***] anniversary of the Effective Date (the &#8220;<font style="font-weight: bold;">Option Term</font>&#8221;), which notice will identify
                one or more targets that Metagenomi proposes to designate as Metagenomi Targets to which the applicable Metagenomi Product will be directed (each, a &#8220;<font style="font-weight: bold;">Proposed Metagenomi Target</font>&#8221; and such notice, a &#8220;<font style="font-weight: bold;">Proposed Metagenomi Target Notice</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1a5b1c4231a74cf286bad0b327593a98" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.7.3._Encumbrance_Check."></a><font style="font-weight: bold;">2.7.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Encumbrance Check</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z11ee3e00c75344a98479aa62a5aa0f9f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Encumbered_Targets._Ionis_will_notif"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Encumbered Targets</font>. Ionis will notify Metagenomi within [***] after Ionis&#8217; receipt of a Proposed Metagenomi Target Notice if, at the time of receipt of such notice, (i)
                [***], (ii) [***], or (iii) [***] (each of (i) through (iii), a &#8220;<font style="font-weight: bold;">Pre-Existing Ionis Restriction</font>&#8221; and such Proposed Metagenomi Target, an &#8220;<font style="font-weight: bold;">Encumbered Proposed
                  Metagenomi Target</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z967337d9da5446568f23e945b6a43e37" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Effects_if_a_Proposed_Metagenomi_Tar"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Effects if a Proposed Metagenomi Target is not an Encumbered Proposed Metagenomi Target</font>. If Ionis does not notify Metagenomi within [***] after Ionis&#8217; receipt of a
                Proposed Metagenomi Target Notice that the applicable Proposed Metagenomi Target is an Encumbered Proposed Metagenomi Target, then Metagenomi may provide a second notice to Ionis indicating that the Proposed Metagenomi Target will be deemed
                a &#8220;Metagenomi Target&#8221; if Ionis does not respond to such second notice within [***]. If Ionis (i) notifies Metagenomi that a Proposed Metagenomi Target is not an Encumbered Proposed Metagenomi Target or (ii) does not provide notice that a
                Proposed Metagenomi Target is an Encumbered Proposed Metagenomi Target within the original [***] period or within [***] after Metagenomi&#8217;s second notice (such date, the &#8220;<font style="font-weight: bold;">Ionis IP Option Effective Date</font>&#8221;),


                then, in either case, (A) the Proposed Metagenomi Target will automatically be deemed to be a &#8220;Metagenomi Target&#8221; under this Agreement with no further action by the Parties, and (B) the license to Metagenomi under <u>Section</u>&#160;<u>3.2.3(a)</u>
                (Ionis Background Technology License Grant) will be effective with respect to Metagenomi Products for such Metagenomi Target.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">9</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z9d1940d08bbc4999a520772fa3d410f3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z2.7.4._Ionis_Background_Technology_Trans"></a><font style="font-weight: bold;">2.7.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Background Technology Transfer</font>. On a Metagenomi Target-by-Metagenomi Target basis, no later than [***] after the Ionis IP Option Effective Date for each
                Metagenomi Target, Ionis will transfer to Metagenomi all Ionis Background Technology that is [***], for Metagenomi to Exploit the applicable Metagenomi Product for such Metagenomi Target in the Field.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_TOC_250033"></a>Article 3 </div>
      <div style="text-align: center; font-weight: bold;">Licenses; Exclusivity</div>
      <div style="text-align: center;">&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z612c6ddcaee1400a8313ff340cddad4b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark25"></a><a name="z_TOC_250032"></a><font style="font-weight: bold;">3.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">License Grants to Ionis</font>.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z0f057eb60e67448b859b8313277ad3dc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.1.1._Collaboration_Activities_License."></a><font style="font-weight: bold;">3.1.1.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Collaboration Activities License</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9a90ca5b0ff04c7295be715101a8c5b5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Collaboration_Activities_License_Gra"></a><a name="z_bookmark26"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Collaboration Activities License Grant</font>. Subject to the terms of this Agreement, Metagenomi hereby grants to Ionis and its Affiliates a non-exclusive, royalty-free
                license, with the right to sublicense through multiple tiers (subject to <u>Section</u>&#160;<u>3.1.1(b)</u> (Sublicensing by Ionis)), under the Licensed Technology to perform (or have performed in accordance with this Agreement) all
                Collaboration Activities allocated to Ionis under each Collaboration Program Plan during the Collaboration Term.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z698b4435c77d4fd7b68ae3222578a5d1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_bookmark27"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Ionis</font>. Ionis may grant sublicenses of any rights granted by Metagenomi under <u>Section 3.1.1(a)</u> (Collaboration Activities License Grant) through
                multiple tiers to any of its Affiliates or to one or more Subcontractors that are not [***]. Each such sublicense will be consistent with the terms of this Agreement and will require such Sublicensee to comply with all applicable terms of
                this Agreement. Ionis will remain responsible for its Sublicensees&#8217; compliance with the applicable terms of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z17cfa289408d416c9efb67a84062fd82" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.1.2._Exclusive_Exploitation_License."></a><font style="font-weight: bold;">3.1.2.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Exclusive Exploitation License</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf3269bb37d2a4c128ec019d7d0b4d44f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Exclusive_Exploitation_License_Grant"></a><a name="z_bookmark28"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exclusive Exploitation License Grant</font>. Subject to the terms of this Agreement, Metagenomi hereby grants to Ionis and its Affiliates an exclusive, royalty-bearing
                license, with the right to sublicense through multiple tiers (subject to <u>Section</u>&#160;<u>3.1.2(c)</u> (Sublicensing by Ionis)), under the Licensed Technology to Exploit all Licensed Systems and Licensed Products solely in the Field in
                the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zba86142ab6a34036bf97a6f2d07ab097" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Limitations._Notwithstanding_the_lic"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Limitations</font>. Notwithstanding the license granted to Ionis pursuant to <u>Section</u>&#160;<u>3.1.1(a)</u> (Collaboration Activities License Grant) and <u>Section 3.1.2(a)</u>
                (Exclusive Exploitation License Grant), subject to the terms of this Agreement, Metagenomi will retain non-exclusive rights under the Licensed Technology in the Field in the Territory for the sole purpose of performing the Metagenomi
                Activities or fulfilling its obligations under this Agreement, in each case, either itself or through its Affiliates, or Subcontractors. For clarity, Metagenomi will retain all rights under the Licensed Technology and Licensed Systems for
                use outside of the Field.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">10</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zddfbce5e610a48849252faa55538d549" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Sublicensing_by_Ionis._Ionis_may_gra"></a><a name="z_bookmark29"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Ionis</font>. Ionis may grant sublicenses of any rights granted by Metagenomi under <u>Section 3.1.2(a)</u> (Exclusive Exploitation License Grant) through
                multiple tiers to any of its Affiliates or to one or more Sublicensees without the consent of Metagenomi; <font style="font-style: italic;">provided </font>that such Sublicensees are not [***]. Each such sublicense will be consistent with
                the terms of this Agreement and will require such Sublicensee to comply with all applicable terms of this Agreement. Ionis will remain responsible for its Sublicensees&#8217; compliance with the applicable terms of this Agreement. Promptly
                following Ionis&#8217; grant of a sublicense to a Sublicensee, Ionis will notify Metagenomi of such sublicense. Upon Metagenomi&#8217;s written request, Ionis will provide Metagenomi with a fully-executed copy of any agreement reflecting any such
                sublicense (excluding any sublicense with an Affiliate of Ionis&#8217; or any Third Party acting on Ionis&#8217; behalf), which may be reasonably redacted to exclude Ionis&#8217; proprietary information, other competitively sensitive information, or any
                other information not necessary for Metagenomi to verify compliance with the preceding sentence, which copy will be treated as Ionis&#8217; Confidential Information.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z39a55bce3f0c4249a7d2918ff8922b42" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.1.3._Unblocking_License."></a><a name="z_bookmark30"></a><font style="font-weight: bold;">3.1.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Unblocking License</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0e1588e9517d43b0b887d439dafe5c46" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_bookmark31"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Unblocking License Grant</font>. Subject to the terms of this Agreement, including the license granted pursuant to <u>Section 3.1.2(a)</u> (Exclusive Exploitation License
                Grant), Metagenomi hereby grants to Ionis and its Affiliates a [***] non-exclusive license, with the right to sublicense through multiple tiers (subject to <u>Section 3.1.3(b)</u> (Sublicensing by Ionis)), under Metagenomi&#8217;s interest in
                the Joint Collaboration Technology [***] in the Unblocking Field in the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z1c131af9ea67429f97afbd086e340c72" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Sublicensing_by_Ionis._Ionis_may_gra"></a><a name="z_bookmark32"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Ionis</font>. Ionis may grant sublicenses of any rights granted by Metagenomi under <u>Section 3.1.3(a)</u> (Unblocking License Grant) through multiple tiers
                to any of its Affiliates or to one or more Sublicensees to which Ionis grants a license to [***]. Each such sublicense will be consistent with the terms of this Agreement and will require such Sublicensee to comply with all applicable terms
                of this Agreement. Ionis will remain responsible for its Sublicensees&#8217; compliance with the applicable terms of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8c279d5161ea4efb91dab76d9e98a63b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250031"></a><font style="font-weight: bold;">3.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">License Grants to Metagenomi</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z085ef56249014562b86c731b4ac81902" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.2.1._Metagenomi_Activities_License."></a><font style="font-weight: bold;">3.2.1.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Metagenomi Activities License</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z10ab969801b64621aaefb6e4c9f0e4b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Metagenomi_Activities_License_Grant."></a><a name="z_bookmark33"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Activities License Grant</font>. Subject to the terms of this Agreement, Ionis hereby grants to Metagenomi a non-exclusive, royalty-free license, with the right to
                sublicense through multiple tiers (subject to the provisions of <u>Section</u>&#160;<u>3.2.1(b)</u> (Sublicensing by Metagenomi)), under the Ionis Licensed Technology solely to perform the Collaboration Activities assigned to Metagenomi under
                the Collaboration Program Plans ( the &#8220;<font style="font-weight: bold;">Metagenomi Activities</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze2862a341a57424bb6e9b2a1bce3807d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_bookmark34"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Metagenomi</font>. Metagenomi may grant sublicenses of any rights granted by Ionis under <u>Section 3.2.1(a)</u> (Metagenomi Activities License Grant) through
                multiple tiers to any of its Affiliates or to one or more Subcontractors that are not [***]. Each such sublicense will be consistent with the terms of this Agreement and will require such Sublicensee to comply with all applicable terms of
                this Agreement. Metagenomi will remain responsible for each Sublicensee&#8217;s compliance with the applicable terms of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">11</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z392c81de05734e66aeba7743b99e7e10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;">&#160;</td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.2.2._Unblocking_License."></a><a name="z_bookmark35"></a><font style="font-weight: bold;">3.2.2.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Unblocking License</font>.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z60009d5c05a640b8b1fc72a840e75354" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Unblocking_License_Grant._Subject_to"></a><a name="z_bookmark36"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Unblocking License Grant</font>. Subject to the terms of this Agreement, Ionis hereby grants to Metagenomi and its Affiliates a [***] non-exclusive license, with the right to
                sublicense through multiple tiers (subject to <u>Section 3.2.2(b)</u> (Sublicensing by Metagenomi)), under Ionis&#8217; interest in the Joint Collaboration Technology [***] in the Unblocking Field in the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z5cca08f1f5ac4a22b7aa0398aa572bc9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="z_bookmark37"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Metagenomi</font>. Metagenomi may grant sublicenses of any rights granted by Ionis under <u>Section 3.2.2(a)</u> (Unblocking License Grant) through multiple
                tiers to any of its Affiliates or to one or more Sublicensees to which Metagenomi grants a license to [***]. Each such sublicense will be consistent with the terms of this Agreement and will require such Sublicensee to comply with all
                applicable terms of this Agreement. Metagenomi will remain responsible for its Sublicensees&#8217; compliance with the applicable terms of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z10ae7c1435b6410180a4daeae9d13c1d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.2.3._Ionis_Background_Technology_Licen"></a><font style="font-weight: bold;">3.2.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis Background Technology License</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8636782093aa49f7b4b9d77756668304" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Ionis_Background_Technology_License_"></a><a name="z_bookmark38"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Background Technology License Grant</font>. Subject to <u>Section 2.7</u> (Ionis Proprietary Toolbox of Chemical Modifications), effective upon the Ionis IP Option
                Effective Date for a Metagenomi Target, Ionis hereby grants to Metagenomi a non-exclusive, royalty-bearing license with the right to grant sublicenses through multiple tiers (subject to <u>Section 3.2.3(b)</u> (Sublicensing by Metagenomi))
                under the Ionis Background Technology solely to Exploit Metagenomi Products for such Metagenomi Target in the Field.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za073a56a453e40b8be51ec488803f74a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Sublicensing_by_Metagenomi._Metageno"></a><a name="z_bookmark39"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicensing by Metagenomi</font>. Metagenomi may grant sublicenses of any rights granted by Ionis under <u>Section 3.2.3(a)</u> (Ionis Background Technology License Grant)
                through multiple tiers to any of its Affiliates or to one or more Sublicensees to which Metagenomi grants a license to Exploit the Metagenomi Products; <font style="font-style: italic;">provided </font>that such Sublicensees are not
                [***]. Each such sublicense will be consistent with the terms of this Agreement and will require such Sublicensee to comply with all applicable terms of this Agreement. Metagenomi will remain responsible for its Sublicensees&#8217; compliance
                with the applicable terms of this Agreement. Promptly following Metagenomi&#8217;s grant of a sublicense to a Sublicensee, Metagenomi will notify Ionis of such sublicense. Upon Ionis&#8217; written request, Metagenomi will provide Ionis with a
                fully-executed copy of any agreement reflecting any such sublicense (excluding any sublicense with an Affiliate of Metagenomi), which may be reasonably redacted to exclude Metagenomi&#8217;s proprietary information, other competitively sensitive
                information, or any other information not necessary for Ionis to verify compliance with the preceding sentence, which copy will be treated as Metagenomi&#8217;s Confidential Information.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">12</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z9470ccbc2fc449cc8d8eb6ff3b799038" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z3.3._Subcontractors._Each_Party_and_its_"></a><a name="z_bookmark40"></a><font style="font-weight: bold;">3.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Subcontractors</font>. Each Party and its Affiliates may perform any of its obligations under this Agreement through one or more Subcontractors; <font style="font-style: italic;">provided </font>that (a) neither Party nor its Affiliates will engage any subcontractor that has been debarred by any Regulatory Authority; (b) the subcontracting Party remains fully responsible for the work allocated to, and
                payment to, such subcontractors to the same extent it would if it had done such work itself; (c) the subcontractor undertakes in writing obligations of confidentiality and non-use applicable to the Confidential Information that are at least
                as stringent as those set forth in <u>Article 11</u> (Confidentiality) other than the term of any such confidentiality obligation, which will be customary for the nature of the Subcontractor; (d) require such Subcontractor and its
                personnel to assign (or, if such Party, after using Commercially Reasonable Efforts, cannot obtain an assignment, then to grant a perpetual license) to such Party of all rights, title, and interests in and to any Patent Rights or Know-How
                created, conceived, or developed in connection with the performance of subcontracted activities; <font style="font-style: italic;">provided </font>that such Subcontractor and its personnel will not be required to assign its rights, title,
                and interests to any of its background intellectual property or improvements thereto; (e) the subcontracting Party will be liable for any act or omission of any Subcontractor that is a breach of any of the subcontracting Party&#8217;s obligations
                under this Agreement as though the same were a breach by the subcontracting Party; (f) each Party will use good faith efforts to identify in writing to the other Party any Subcontractor that it engages to perform Collaboration Activities
                and will only engage Subcontractors to perform the Collaboration Activities to the extent and in a manner consistent with such Party&#8217;s engagement of subcontractors for other internal Development programs; (g) Ionis [***]; and (h) Metagenomi
                [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9638e972f0d0418d86eccc9e97ba9cb2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark41"></a><a name="z_TOC_250030"></a><font style="font-weight: bold;">3.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Technology Transfer</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf1d4c6f4c60144db94568e463346b3f6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.4.1._Initial_Transfers._On_a_Collabora"></a><a name="z_bookmark42"></a><font style="font-weight: bold;">3.4.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Initial Transfers</font>. On a Collaboration Target-by-Collaboration Target basis, no later than (a) for [***], [***] after the Effective Date and (b) for each new
                Collaboration Target, [***] after the applicable target becomes a Collaboration Target pursuant to <u>Section</u>&#160;<u>2.1.1(b)</u> (Second Wave 1 Target) or <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available), each Party
                will transfer to the other Party all Ionis Licensed Technology or Licensed Technology (as applicable), with respect to [***], as of the Effective Date, or, with respect to Collaboration Targets that become such after the Effective Date, at
                the time that a target becomes a Collaboration Target, in each case, that is [***] to perform the activities allocated to the non-transferring Party under the Drug Discovery Plan for the applicable Collaboration Target. In addition, each
                Party will transfer to the other Party all Ionis Licensed Technology or Licensed Technology (as applicable) that is [***] for the non-transferring Party to perform the activities allocated to the non-transferring Party under the Exploratory
                Research Plan no later than [***] after the Effective Date.</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify; margin-right: 5.7pt; margin-left: 86.95pt;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z10b9ef8ed6f244a5a32d938975fad4bf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.4.2._Additional_Transfers._Following_t"></a><font style="font-weight: bold;">3.4.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Transfers</font>. Following the initial transfers described in <u>Section 3.4.1</u> (Initial Transfers), (a) promptly after [***] and (b) at least [***],
                Metagenomi will provide prompt updates to Ionis regarding any Licensed Know-How not previously transferred to Ionis that is [***] Ionis to continue Exploiting the Licensed Systems and Licensed Products[***], that relate to the Development
                Candidates being Exploited, or that Ionis, at such time, intends to Exploit, under this Agreement. During the Term, as reasonably requested by Ionis, Metagenomi will promptly provide Ionis with any information specifically identified by
                Ionis and included in the Licensed Technology that is [***] for Ionis to Exploit the Licensed Systems or Licensed Products that relate to the Development Candidates being Exploited, or that Ionis, at such time, intends to Exploit, and has
                not previously been transferred to Ionis under this Agreement. Metagenomi will provide such information to Ionis within [***] after Ionis&#8217; request.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zed45faa2f6f243c687ba93774d11696d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.4.3._Assistance_by_Metagenomi_Personne"></a><font style="font-weight: bold;">3.4.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Assistance by Metagenomi Personnel</font>. To assist with the transfer of Licensed Know-How under this <u>Section 3.4</u> (Technology Transfer) and Ionis&#8217; Exploitation
                thereof in accordance with the terms of this Agreement during the Term, Metagenomi will make its personnel reasonably available to Ionis during normal business hours to transfer such Licensed Know-How to Ionis and respond to Ionis&#8217;
                reasonable inquiries with respect thereto.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">13</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z4b54e8d750184760979cc9922bf0899c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.4.4._Costs_of_Support._On_a_Collaborat"></a><a name="z_bookmark43"></a><font style="font-weight: bold;">3.4.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Costs of Support</font>. On a Collaboration Program-by-Collaboration Program basis, Metagenomi will provide the first [***] FTE hours of technology transfer, or technical or
                regulatory assistance under this <u>Section 3.4</u> (Technology Transfer), <u>Section 7.2.2</u> (Assistance; Support) and <u>Section 7.3</u> (Regulatory Support) for a Collaboration Program at Metagenomi&#8217;s cost and expense. On a
                Collaboration Program-by-Collaboration Program basis, for any such assistance in excess of [***] FTE hours for a Collaboration Program, Ionis will reimburse Metagenomi for [***] with respect thereto within [***] of receipt of a reasonably
                detailed invoice therefor.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z701215aa643a4f9f9d50b7ff6907c25d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z3.5._No_Implied_Licenses._Except_as_expr"></a><a name="z_bookmark44"></a><font style="font-weight: bold;">3.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">No Implied Licenses</font>. Except as expressly provided in this Agreement, neither Party will be deemed to have granted the other Party any license or other right with
                respect to any Intellectual Property Rights of such Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdc6bfda22d854a89a50858e190ad4146" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark45"></a><a name="z_TOC_250029"></a><font style="font-weight: bold;">3.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Exclusivity</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze1636a46e8df493caea945fbbb33dfb6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.6.1._Exclusivity_Obligations._Subject_"></a><a name="z_bookmark46"></a><font style="font-weight: bold;">3.6.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exclusivity Obligations</font>. Subject to <u>Section 3.6.2</u> (Acquisition of Distracting Product) and <u>Section 3.6.3</u> (Change of Control), except in the performance
                of its obligations or exercise of its rights under this Agreement, neither Party nor any of its Affiliates will work independently or for or with any Third Party (including the grant of any license to any Third Party) to:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd8d6fc8fee344ba4877defe387e6d47c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_on_a_Drug_Discovery_Program-by-Drug_"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">on a Drug Discovery Program-by-Drug Discovery Program basis, (i) during the Drug Discovery Term for a Drug Discovery Program, Develop or Commercialize any product that targets the Collaboration Target in the
                Exclusivity Field, and (ii) until the earlier of the (1) [***] period after the expiration of the Drug Discovery Term for a Drug Discovery Program or (2) [***] period after the Effective Date, clinically Develop or Commercialize any product
                that targets a Collaboration Target in the Exclusivity Field that is actively being Developed by Ionis under this Agreement for such Drug Discovery Program; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z169b1be6b31e47978feaa92b628d3086" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_on_a_Co-Co_Program-by-Co-Co_Program_"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">on a Co-Co Program-by-Co-Co Program basis, during the period commencing on the date [***] and expiring upon [***] for such Co-Co Program, Develop or Commercialize any product that targets the Collaboration
                Target for such Co-Co Program in the Exclusivity Field.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="margin: 0px 0px 0px 87pt; text-align: justify;"><a name="For_clarity_the_limitations_set_forth_i"></a>For clarity, the limitations set forth in this <u>Section 3.6.1</u> (Exclusivity Obligations) will not apply to any Collaboration
        Target that is substituted out in accordance with <u>Section 2.1.3</u> (Target Substitutions).</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc61cb54b5fe841caab2ffed84c9afd8f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.6.2._Acquisition_of_Distracting_Produc"></a><a name="z_bookmark47"></a><font style="font-weight: bold;">3.6.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Acquisition of Distracting Product</font>. Notwithstanding the provisions of <u>Section 3.6.1</u> (Exclusivity Obligations), if a Party or any of its Affiliates (such Party,
                the &#8220;<font style="font-weight: bold;">Distracted Party</font>&#8221;) acquires rights to Develop or Commercialize a product in the Field as the result of a merger, acquisition, or combination with or of a Third Party (where such Party is not the
                acquired entity) other than a Change of Control (each, an &#8220;<font style="font-weight: bold;">Acquisition Transaction</font>&#8221;) and, on the date of the closing of such Acquisition Transaction, such product is being Developed or Commercialized
                and such activities would, but for the provisions of this <u>Section 3.6.2</u> (Acquisition of Distracting Product), constitute a breach of <u>Section 3.6.1</u> (Exclusivity Obligations) (such product, a &#8220;<font style="font-weight: bold;">Distracting




                  Product</font>&#8221;), then the Distracted Party or such Affiliate will, within [***] after the closing of such Acquisition Transaction notify the other Party in writing of such acquisition and either:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">14</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z3c21c0aa5f904a3981f157bd9595d851" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_request_that_such_Distracting_Produc"></a><a name="z_bookmark48"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">request that such Distracting Product be included in this Agreement on terms to be negotiated, in which case, the Parties will discuss the matter in good faith for a period of no less than [***] (or such
                longer period as may be agreed by the Parties) and, if the Parties are unable to reach agreement on the terms on which such Distracting Product would be included hereunder within such period, then the Distracted Party will elect to take the
                action specified in either <u>Section 3.6.2(b)</u> or <u>Section 3.6.2(c)</u> below; <font style="font-style: italic;">provided </font>that the time periods specified in such clauses will be tolled for so long as the Parties are engaged
                in good faith discussion under this <u>Section 3.6.2(a)</u>;</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zed38866456384786917705e1c63ae1a3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_notify_the_other_Party_in_writing_th"></a><a name="z_bookmark49"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">notify the other Party in writing that the Distracted Party or its Affiliate will [***], in which case, within [***] after the closing of the Acquisition Transaction, the Distracted Party or its Affiliate
                will [***]; or</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z53378bd494e44b94bb757db7299974c9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_notify_the_other_Party_in_writing_th"></a><a name="z_bookmark50"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">notify the other Party in writing that it [***], in which case, within [***] after the other Party&#8217;s receipt of such notice, the Distracted Party and its Affiliates will [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="margin: 0px 0px 0px 86.95pt; text-align: justify; text-indent: 36pt;">During the discussion period under <u>Section 3.6.2(a)</u>, prior to the time of [***] pursuant to <u>Section 3.6.2(b)</u>, or prior to the [***] pursuant to <u>Section


          3.6.2(c)</u>, as applicable, the Distracted Party and its Affiliates will segregate all activities relating to the Distracting Product from the Exploitation of the Licensed Systems or Licensed Products under this Agreement, including ensuring
        that (i) no personnel involved in performing Development or Commercialization activities with respect to such Distracting Product have access to non-public plans or information relating to the Development or Commercialization of Licensed Systems or
        Licensed Products under this Agreement (except that [***]), and (ii) no personnel involved in performing Development or Commercialization activities with respect to Licensed Systems or Licensed Products under this Agreement have access to
        non-public plans or information relating to the Development or Commercialization of such Distracting Product (except that [***]). The procedures set forth in clauses (i) and (ii) above will be referred to as &#8220;<font style="font-weight: bold;">Firewall


          Procedures</font>&#8221; for the purposes of this Agreement.</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0b3345cbe9c44c1995cf1dc1700167b0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z3.6.3._Change_of_Control._If_there_is_a_"></a><a name="z_bookmark51"></a><font style="font-weight: bold;">3.6.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Change of Control</font>. If there is a Change of Control involving a Party (where such Party is the acquired entity), then:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1daca5cae0b24d939c7463267988996d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_the_obligations_of_Section_3.6.1_Ex"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the obligations of <u>Section 3.6.1</u> (Exclusivity Obligations) will not apply to any product that is controlled by the relevant acquirer or its Affiliates and that exists prior to the closing of such
                Change of Control; <font style="font-style: italic;">provided </font>that (i) the acquired Party and the acquirer and its Affiliates existing immediately prior to the effective date of such Change of Control [***], (ii) the acquirer and
                its Affiliates existing immediately prior to the effective date of such Change of Control [***], and (iii) no personnel who were employees or consultants of the acquired Party or its Affiliates at any time prior to or after the Change of
                Control will [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1f4fd5bd2ac640f883b058ecfa3363b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_if_Ionis_is_the_acquired_entity_and_"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">if Ionis is the acquired entity and the acquiring entity is [***], then Ionis will ensure that the acquiring entity establishes and implements Firewall Procedures to segregate and protect Confidential
                Information related to the Licensed Systems and Licensed Products from access to or use by the acquiring party other than as permitted by this Agreement; and</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">15</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z3321472548f64325840cdccd23e1366f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_if_Metagenomi_is_the_acquired_entity"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">if Metagenomi is the acquired entity and the acquiring entity is [***], then Metagenomi will ensure that the acquiring entity establishes and implements Firewall Procedures to segregate and protect
                Confidential Information related to the Licensed Systems, Licensed Products, and Ionis Background Technology from access to or use by the acquiring party other than as permitted by this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark52"></a><a name="z_TOC_250028"></a>Article 4 </div>
      <div style="text-align: center; font-weight: bold;">Governance</div>
      <div style="text-align: center;">&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z33f4d1ec08124e83a97b0184ca335528" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark53"></a><a name="z_TOC_250027"></a><font style="font-weight: bold;">4.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Joint Steering Committee</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z66b1ea27d19f4eff9a0493a23286cbaa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.1.1._Formation_and_Purpose_of_the_JSC."></a><font style="font-weight: bold;">4.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Formation and Purpose of the JSC</font>. Promptly, but no later than [***] after the Effective Date, the Parties will establish a Joint Steering Committee (&#8220;<font style="font-weight: bold;">JSC</font>&#8221;), which JSC will coordinate, oversee, and monitor the Parties&#8217; activities hereunder in accordance with this <u>Section 4.1</u> (Joint Steering Committee). The JSC will have the responsibilities set
                forth herein and will have no further responsibilities (a) with respect to the Exploratory Research Program, upon the expiration of the Exploratory Research Term, and (b) with respect to any Drug Discovery Program, upon the expiration of
                the Drug Discovery Term for such Drug Discovery Program. Upon the latest to occur of (a)-(b), the JSC will be dissolved.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4c627d7217ed47e183d7ee01ad62aa06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.1.2._Membership._Each_Party_will_desig"></a><font style="font-weight: bold;">4.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Membership</font>. Each Party will designate [***] representatives with appropriate expertise and seniority to serve as members of the JSC, and who have the authority to bind
                such Party with respect to matters within the purview of the JSC. Each Party may replace its JSC representatives at any time upon written notice to the other Party. Metagenomi will designate one of its JSC members as one of the
                co-chairpersons of the JSC and Ionis will designate one of its members as the other co-chairperson of the JSC. Every [***] the co-chairpersons will alternate serving in the role of &#8220;lead co-chairperson.&#8221; The lead co- chairperson or his or
                her designee, in collaboration with the Alliance Managers, will be responsible for calling meetings, preparing and circulating an agenda in advance of each meeting, and preparing and issuing minutes of each meeting within [***] thereafter.
                Such minutes will be deemed finalized unless any JSC member objects to the accuracy of such minutes no later than [***] after receipt of such minutes.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z04abc34393c142ae95ff6741b6e7c55e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.1.3._Meetings._The_JSC_will_meet_in_pe"></a><font style="font-weight: bold;">4.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Meetings</font>. The JSC will meet in person, by videoconference, or by teleconference at least once each [***], unless otherwise agreed by the Parties, on such dates and at
                such times and places as agreed to by the members of the JSC. The Alliance Manager of each Party will attend each meeting of the JSC as a non-voting participant. Each Party will be responsible for all of its own expenses in participating in
                any JSC meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf1dee9587b9f4776b24685aadccb2fae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.1.4._Meeting_Agendas._Each_Party_will_"></a><font style="font-weight: bold;">4.1.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Meeting Agendas</font>. Each Party will disclose to the other Party the proposed agenda items at least [***] in advance of each meeting of the JSC. Notwithstanding the
                foregoing, under exigent circumstances requiring JSC input, a Party may provide its agenda items to the other Party within a lesser period of time in advance of the meeting, or may propose that there not be a specific agenda for a
                particular meeting, so long as such other Party consents to such later addition of such agenda items or the absence of a specific agenda for such JSC meeting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z594142d4e8f54efdbe9faeae0407bb5c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z4.1.5._Specific_Responsibilities_of_the_"></a><a name="z_bookmark54"></a><font style="font-weight: bold;">4.1.5.</font></td>
            <td style="vertical-align: top; width: auto;">
              <div><font style="font-weight: bold;">Specific Responsibilities of the JSC</font>. The responsibilities of the JSC will be to:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zec0efb107ec9440eb4ab5c7e4d1e488c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_oversee_the_overall_strategic_relati"></a>(a)</td>
            <td style="vertical-align: top;">
              <div>oversee the overall strategic relationship between the Parties;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1b5e798cc7dd42c68869fccd8a4e0cf2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_review_discuss_and_determine_wheth"></a><a name="z_bookmark55"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review, discuss, and determine whether it is technologically infeasible to Develop a Development Candidate for a given Collaboration Target, as described in <u>Section&#160;2.1.3(b)</u> (Substitutions for
                Technological Infeasibility);</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">16</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z87b7806d38cc4a9a8699ede59d5d0ec3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_review_discuss_and_determine_wheth"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review, discuss, and determine whether to approve each Drug Discovery Plan, and any updates thereto, pursuant to <u>Section 2.2.2</u> (Additional Drug Discovery Plans) and <u>Section 2.2.3</u> (Amendments
                to the Drug Discovery Plans);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1efa42678eeb489489027604802e2065" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zd_discuss_and_determine_the_Gene_Editi"></a>(d)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">discuss and determine the [***] for the Second Wave 1 Target and each Proposed Target that is deemed a Collaboration Target under this Agreement pursuant to <u>Section 2.1.4(c)</u> (Effects if a Proposed
                Target is Available), as described in <u>Section 2.2.4(b) </u>(Selection of Gene Editing Modalities);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7140583bcd4144b283b6a78d29474cce" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="ze_review_and_discuss_each_Development_"></a>(e)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review and discuss each Development Candidate Report and any other data or results provided by Metagenomi regarding therapeutic agents that meet the development candidate criteria set forth in a Drug
                Discovery Plan, pursuant to <u>Section 2.2.6</u> (Delivery of Development Candidate; Development Candidate Report);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6dc98a33895f4dc981fad0300cdbb8b9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zf_review_discuss_and_determine_wheth"></a>(f)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review, discuss, and determine whether to approve any updates to the Exploratory Research Plan or Exploratory Research Budget, pursuant to <u>Section 2.3.2</u> (Amendments to the Exploratory Research Plan);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4d73fc4206e24e059dcb68a79a59e9be" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zg_review_and_discuss_each_Collaboratio"></a>(g)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review and discuss each Collaboration Program Report, pursuant to <u>Section 2.6.2</u> (Collaboration Program Reports);</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z4cc3b9aeaccd49d8b88d647841177d6c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zh_review_and_discuss_the_Regulatory_St"></a>(h)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">review and discuss the Regulatory Strategy for each Licensed Product, as described in <u>Section 7.1</u> (Regulatory Responsibility);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2bf84580ddb94273b1f4a7bb0eaf0ddb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zi_coordinate_the_wind-down_of_any_Term"></a>(i)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">coordinate the wind-down of any Terminated Products in the Terminated Countries to the extent the JSC is still in effect at the time of the applicable termination notice, pursuant to <u>Section 14.3.1</u>
                (Wind-Down); and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6168806766b645e4b36437c447c592c4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zj_perform_such_other_functions_as_appr"></a>(j)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">perform such other functions as appropriate to further the purposes of this Agreement as determined by the Parties.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zbd36875d2a504b49ad4233bc3b6ae876" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z4.2._Subcommittees._From_time_to_time_t"></a><a name="z_bookmark56"></a><font style="font-weight: bold;">4.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Subcommittees</font>. From time to time, the JSC may establish and delegate duties, including any responsibilities of the JSC set forth in <u>Section 4.1.5</u> (Specific
                Responsibilities of the JSC), to operational subcommittees (each, a &#8220;<font style="font-weight: bold;">Subcommittee</font>&#8221;) on an &#8220;as-needed&#8221; basis to oversee particular projects or activities, which delegations will be reflected in the
                minutes of the meetings of the JSC. Such Subcommittees may be established on an <font style="font-style: italic;">ad hoc </font>basis for purposes of a specific project, for the life of a Licensed Product, or on such other basis as the
                JSC may determine, and will be constituted and will operate as the JSC may determine; <font style="font-style: italic;">provided </font>that each Subcommittee will have equal representation from each Party and decision making will be by
                consensus, with each Party&#8217;s representatives on the applicable Subcommittee collectively having one vote on all matters brought before the Subcommittee. Each Subcommittee and its activities will be subject to the direction, review, and
                approval of, and, unless otherwise determined by the JSC, will report to, the JSC. For each Subcommittee, Ionis will designate one of its Subcommittee members to serve as the chairperson of such Subcommittee. The chairperson or his or her
                designee, in collaboration with the Alliance Managers, will be responsible for calling meetings, preparing and circulating an agenda in advance of each meeting, and preparing and issuing minutes of each meeting within [***] thereafter. Such
                minutes will not be finalized until all Subcommittee members have had an adequate opportunity to review and confirm the accuracy of such minutes. Each Party may replace its representatives on each such Subcommittee at any time upon written
                notice to the other Party. The Alliance Manager of each Party (or his or her designee) will attend each meeting of each Subcommittee as a non-voting participant. Each Subcommittee and its activities will be subject to the oversight of, and
                will report to, the JSC. Any disagreement between the representatives of the Parties on a Subcommittee will be referred to the JSC for resolution in accordance with <u>Section 4.6</u> (Decision-Making).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">17</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zec15de788a654bc79547bc145bf4a8be" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark57"></a><a name="z_TOC_250026"></a><font style="font-weight: bold;">4.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Joint Research Committee</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z29108e5a76be4653a7e2272323e2991c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.3.1._Formation_and_Purpose_of_the_JRC."></a><font style="font-weight: bold;">4.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Formation and Purpose of the JRC</font>. Promptly, but no later than [***] after the creation of the JSC, the Parties will establish a Joint Research Committee (&#8220;<font style="font-weight: bold;">JRC</font>&#8221;), which JRC will coordinate, oversee, and monitor the Parties&#8217; research activities hereunder in accordance with this <u>Section 4.3</u> (Joint Research Committee). The JRC will be deemed a
                &#8220;Subcommittee&#8221; as described in <u>Section 4.2</u> (Subcommittees). The JRC will have the responsibilities set forth herein and will dissolve upon the earlier of (a) the dissolution of the JSC, (b) the expiration of the Collaboration Term,
                or (c) by mutual agreement between the Parties.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb96aaafd4d0f4b11a2a5ab24a9654c36" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.3.2._Membership._Each_Party_will_desig"></a><font style="font-weight: bold;">4.3.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Membership</font>. Each Party will designate [***] representatives with appropriate expertise and seniority to serve as members of the JRC, and who have the authority to bind
                such Party with respect to matters within the purview of the JRC.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8515c2fd9ff14e0f8c5969488f5e4c58" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.3.3._Specific_Responsibilities_of_the_"></a><font style="font-weight: bold;">4.3.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Specific Responsibilities of the JRC</font>. The responsibilities of the JRC will be to:</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z961b247b68c64609b1447e8ae017884e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_coordinate_the_Collaboration_Activit"></a>(a)</td>
            <td style="vertical-align: top;">
              <div>coordinate the Collaboration Activities;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z29a462fb926946ee985ba77628b082c0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_develop_discuss_and_submit_to_the_"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">develop, discuss, and submit to the JSC to further review, discuss, and determine whether to approve each Drug Discovery Plan, and any updates thereto, pursuant to <u>Section 2.2.2</u> (Additional Drug
                Discovery Plans) and <u>Section 2.2.3</u> (Amendments to the Drug Discovery Plans);</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z60fbf19307114a7181510d62cb7f343b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_develop_discuss_and_submit_to_the_"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">develop, discuss, and submit to the JSC to further review, discuss, and determine whether to approve any updates to the Exploratory Research Plan or Exploratory Research Budget, pursuant to <u>Section 2.3.2</u>
                (Amendments to the Exploratory Research Plan); and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z24188846994844dd9538dc32d77783b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zd_perform_such_other_functions_as_dete"></a>(d)</td>
            <td style="vertical-align: top;">
              <div>perform such other functions as determined by the JSC.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9dc068dc356d4437bc2763dea8e09daf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z4.4._Alliance_Managers._Each_of_the_Part"></a><font style="font-weight: bold;">4.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Alliance Managers</font>. Each of the Parties will appoint a single individual to coordinate communications regarding the activities under this Agreement (each, an &#8220;<font style="font-weight: bold;">Alliance Manager</font>&#8221;). The role of the Alliance Manager is to act as a single point of contact between the Parties to ensure a successful relationship under this Agreement. The Alliance Managers will attend
                any JSC meetings. Alliance Managers will be non-voting participants in all JSC meetings that they attend; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that an Alliance Manager may
                bring any matter to the attention of the JSC if such Alliance Manager reasonably believes that such matter warrants such attention. Each Party will designate its initial Alliance Manager promptly after the Effective Date and each Party may
                change its designated Alliance Manager at any time upon written notice to the other Party. Any Alliance Manager may designate a substitute to temporarily perform the functions of that Alliance Manager by written notice to the other Party.
                Each Alliance Manager may also: (a) be the point of first referral in all matters of conflict resolution; (b) provide a single point of communication for seeking consensus between the Parties regarding key strategy and plan issues; (c)
                identify and bring disputes to the attention of the JSC in a timely manner; and (d) plan and coordinate cooperative efforts.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">18</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zd22b739aae8444d78eaffbf9f5f51bb2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 14.9pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.5._Additional_Participants._Other_empl"></a><font style="font-weight: bold;">4.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Participants</font>. Other employees of either Party or any of its Affiliates may attend meetings of the JSC or any Subcommittees as non-voting participants with
                prior written notice to the other Party (including via email notification). In addition, with the consent of each Party, consultants, representatives, or advisors may attend meetings of the JSC or any Subcommittees as non-voting observers;
                <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that such Third Party participants and observers are under written obligations of confidentiality and non-use applicable to the
                Confidential Information of each Party that are at least as stringent as those set forth in <u>Article 11</u> (Confidentiality).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdfd4043d16a74afeab08269e4864062b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark58"></a><a name="z_TOC_250025"></a><font style="font-weight: bold;">4.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Decision-Making</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8afefcab9947400a960b9b2b65e56570" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.6.1._Committee_Decisions._Each_Partys"></a><font style="font-weight: bold;">4.6.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Committee Decisions</font>. Each Party&#8217;s representatives on the JSC will, collectively, have one vote (the &#8220;<font style="font-weight: bold;">Party Vote</font>&#8221;) on all matters
                brought before such committee for a decision by consensus. The JSC will make decisions as to matters within its jurisdiction by unanimous Party Vote, which Party Vote will be reflected in the minutes of the committee meeting. No vote will
                be binding on either Party unless each Party has at least one representative in attendance.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9125f9b60d2c41358379f3c49ab5e41d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.6.2._Scope_of_Committee_Authority._For"></a><font style="font-weight: bold;">4.6.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Scope of Committee Authority</font>. For the avoidance of doubt, matters that are specified in this <u>Article 4</u> (Governance) only to be reviewed and discussed (as
                opposed to reviewed, discussed, and approved) do not require any agreement or decision by either Party and are not subject to the voting and decision-making procedures set forth in this <u>Section 4.6</u> (Decision-Making).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zff36f2bf96f54e9998d9ee67de25a71f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.6.3._Escalation._If_the_representative"></a><font style="font-weight: bold;">4.6.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Escalation</font>. If the representatives of Metagenomi and Ionis are unable to agree on or resolve any matter requiring the approval of the JSC after the use of good faith
                efforts, within [***] after the JSC first considers such matter then, at the election of either Party, such Party may refer such matter to the Party&#8217;s respective Executive Officer. The Executive Officers will use good faith efforts to
                resolve any such disagreement so referred to them as soon as practicable, and any final decision that the Executive Officers agree to in writing will be conclusive and binding on the Parties. If the Executive Officers are unable to resolve
                any such disagreement so referred to them within [***] following such referral (or such longer period as the Executive Officers may agree upon), then:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z97f45dfacede4243aae281aae96a13f4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Ionis_Final_Decision-Making_Authorit"></a><a name="z_bookmark59"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Final Decision-Making Authority</font>. Ionis will have the right to make the final decision regarding [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z791f3d2e67964cbd9b64e5a3bfeb496a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Resolution_by_Baseball_Arbitration._"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Resolution by Baseball Arbitration</font>. Except for those matters set forth in <u>Section&#160;4.6.3(a)</u> (Ionis Final Decision-Making Authority), either Party may refer the
                matter for resolution pursuant to <u>Section 15.1.3</u> (Expedited Dispute Resolution).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7de07cf215734040af8e1a1a4e123595" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z4.6.4._General_Authority._The_JSC_and_an"></a><font style="font-weight: bold;">4.6.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">General Authority</font>. The JSC and any Subcommittees will have solely the powers expressly assigned to them in this <u>Article 4</u> (Governance) and elsewhere in this
                Agreement. In conducting themselves on the JSC, any Subcommittees, and as Alliance Managers, and in exercising their rights under this <u>Article 4</u> (Governance), all representatives of each Party will consider diligently, reasonably,
                and in good faith all input received from the other Party, and will use good faith efforts to reach unanimity, where required, on all matters before them. Notwithstanding anything to the contrary set forth in this Agreement, the JSC, and
                any Subcommittees will not have the right to make any decisions: (a) to amend, modify, or waive compliance with any term or condition of this Agreement; (b) in a manner that negates any consent right or other right specifically allocated to
                a Party under this Agreement; (c) to resolve any dispute involving the breach or alleged breach of this Agreement; (d) to resolve a matter if the provisions of this Agreement specify that agreement of the Parties, including consent of each
                Party, is required for such matter; (e) in a manner that a Party reasonably believes would require it to perform any act that would cause such Party to violate any Applicable Law or the requirements of any Regulatory Authority, or otherwise
                breach any of its obligations hereunder; or (f) that otherwise expand the rights or reduce the obligations of either Party under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">19</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="Article_5__Co-Development_and_Co-Commerc"></a>Article 5</div>
      <div style="text-align: center; font-weight: bold;">Co-Development and Co-Commercialization Options</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za4c5d1b48a0f43f0a97a365be0af7790" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z5.1._Co-Development_and_Co-Commercializa"></a><a name="z_bookmark60"></a><font style="font-weight: bold;">5.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Co-Development and Co-Commercialization Options</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8b094473af2c4f0ea14a9ae45b884481" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z5.1.1._Option_Grant._Ionis_hereby_grants"></a><font style="font-weight: bold;">5.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Grant</font>. Ionis hereby grants to Metagenomi the exclusive option to co-Develop and co-Commercialize with Ionis the Licensed Products under a Drug Discovery Program
                (a &#8220;<font style="font-weight: bold;">Co-Co Option</font>&#8221;), which Co-Co Option may be exercised for (a) [***], (b) no more than [***] of the other [***] Drug Discovery Programs for the Wave 1 Targets, and (c) no more than [***] Drug
                Discovery Programs for the Wave 2 Targets that become Collaboration Targets.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0992ed44cfcb4ee6acd65b385bfc4a18" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z5.1.2._Option_Period._On_a_Drug_Discover"></a><font style="font-weight: bold;">5.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Period</font>. On a Drug Discovery Program-by-Drug Discovery Program basis, Metagenomi may exercise a Co-Co Option for a Drug Discovery Program by delivering written
                notice to Ionis of such exercise at any time during the [***] period after the selection of [***] for such Drug Discovery Program (such notice, the &#8220;<font style="font-weight: bold;">Co-Co Option Notice</font>&#8221;, and such [***] period, the &#8220;<font style="font-weight: bold;">Co-Co Option Period</font>&#8221;). Notwithstanding the foregoing, Metagenomi may terminate the Co-Co Option Period for a Drug Discovery Program early by providing written notice to Ionis at any time during such [***]
                period that Metagenomi does not elect to exercise its Co-Co Option for such Drug Discovery Program and, upon Ionis&#8217; receipt of any such written notice the Co-Co Option Period for such Drug Discovery Program, the Co-Co Option Period for such
                Drug Discovery Program will be deemed to have expired and Metagenomi may not thereafter exercise the Co-Co Option for such Drug Discovery Program. No more than [***] at Metagenomi&#8217;s request during the Co-Co Option Period for a Drug
                Discovery Program, Ionis will provide Metagenomi with [***] (&#8220;<font style="font-weight: bold;">Option Package</font>&#8221;). For clarity, Ionis will not be required to generate any additional data or information that is not in existence as of
                the date of Metagenomi&#8217;s request for an Option Package.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zecca3551372d4de4ae20d0ca3b391c9e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z5.1.3._Option_Exercise._If_Metagenomi_de"></a><a name="z_bookmark61"></a><font style="font-weight: bold;">5.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Exercise</font>. If Metagenomi decides to exercise the Co-Co Option for a particular Drug Discovery Program, then it will deliver written notice to Ionis of such
                determination during the applicable Co-Co Option Period, which notice will indicate the Drug Discovery Program for which Metagenomi elects to exercise the Co-Co Option, and (a) the Drug Discovery Program for which Metagenomi is exercising
                its Co-Co Option will automatically be deemed a &#8220;Co-Co Program&#8221; and all Licensed Products under such Drug Discovery Program will automatically be deemed &#8220;Co-Co Products,&#8221; (b) Metagenomi will pay Ionis the Option Exercise Fee for such Co-Co
                Program pursuant to <u>Section 9.3</u> (Option Exercise Fee), and (c) the Parties will enter into a Co-Development and Co- Commercialization Agreement for such Co-Co Program in accordance with <u>Section 5.2</u> (Development and
                Commercialization of the Co-Co Products; Opt-Down Right). Any Drug Discovery Program for which Metagenomi does not exercise a Co-Co Option prior to the expiration of the applicable Co-Co Option Period will automatically be deemed an &#8220;Ionis
                Program&#8221; and all Licensed Products under such Drug Discovery Program will automatically be deemed &#8220;Ionis Products&#8221; and Ionis will have sole control under the Development and Commercialization of such Ionis Products in accordance with <u>Article


                  6</u> (Development and Commercialization of the Ionis Products).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">20</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z57aec2ffa307471e820f95812ebfda71" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z5.2._Development_and_Commercialization_o"></a><a name="z_bookmark62"></a><font style="font-weight: bold;">5.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Development and Commercialization of the Co-Co Products; Opt-Down Right</font>. On a Co-Co Program-by-Co-Co Program basis, promptly after Metagenomi exercises a Co-Co Option
                for a Co- Co Program, the Parties will negotiate in good faith the terms of a worldwide, co-exclusive (with Ionis) co-Development and co-Commercialization agreement (the &#8220;<font style="font-weight: bold;">Co-Development and Co-
                  Commercialization Agreement</font>&#8221;), which terms and conditions will be reasonable and customary for agreements of this type and will include a requirement that the Parties share all future Development, Commercialization, and other
                Exploitation costs and all future profits with respect to the applicable Co-Co Products, with the Parties bearing the share of such costs [***] and Ionis being responsible for booking and recording revenue and on terms to be specified in
                the Co- Development and Co-Commercialization Agreement; <font style="font-style: italic;">provided</font>, that [***]. Each Co-Development and Co-Commercialization Agreement will include: (i) the right for Metagenomi to, upon written
                notice to Ionis, reduce its share of any costs borne under the applicable Co-Co Program from [***]% to any percentage between [***]% and [***]% and Ionis&#8217; share of such costs will increase accordingly (such option, the &#8220;<font style="font-weight: bold;">Opt-Down Right</font>&#8221;); <font style="font-style: italic;">provided </font>that Metagenomi will continue to bear [***]% of the costs of [***], (ii) each Party will receive a share of profits equal to the
                percentage of costs funded by such Party following the exercise of the Opt-Down Right based on the percentage of costs that Metagenomi commits to funding in its notice of exercise of its Opt-Down Right, and (iii) Metagenomi may only
                exercise the Opt-Down Right during the period beginning no earlier than [***] and no later than [***] prior to the [***]. Until the Parties execute the Co-Development and Co-Commercialization Agreement, Ionis will continue to conduct and
                will be solely responsible for, and continue to have sole and exclusive control over, the Development and Manufacture of the applicable Co-Co Products.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb95437e58f43459c8403fcfba9aaa05c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z5.3._Escalation_Procedure._If_the_Partie"></a><font style="font-weight: bold;">5.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Escalation Procedure</font>. If the Parties, despite their good faith negotiations, are unable to agree on the terms and conditions of any Co-Development and
                Co-Commercialization Agreement within [***] of the date of the applicable Co-Co Option Notice (or such longer time as mutually agreed by the Parties), then either Party may refer those terms and conditions to which they have not mutually
                agreed to the Executive Officers, who will use reasonable efforts to reach agreement on such terms and conditions. If such Executive Officers are unable to reach consensus with respect to such terms and conditions within [***] after such
                referral, then either Party may notify the other Party of its intent to invoke dispute resolution under <u>Section 15.1.3</u> (Expedited Dispute Resolution).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3559214be8264c58a89c5540dfad4ff2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z5.4._Metagenomi_Opt-Out._On_a_Co-Co_Prog"></a><a name="z_bookmark63"></a><font style="font-weight: bold;">5.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Opt-Out</font>. On a Co-Co Program-by-Co-Co Program basis, Metagenomi will have the right to opt-out of its rights and obligations under this Agreement to the
                extent related to the Exploitation of the Co-Co Products under such Co-Co Program and the applicable Co- Development and Co-Commercialization Agreement for a Co-Co Program (each such right, an &#8220;<font style="font-weight: bold;">Opt-Out Right</font>&#8221;).


                Metagenomi may exercise the Opt-Out Right for a Co-Co Program by providing written notice to Ionis of such election no later than [***] after [***] (the &#8220;<font style="font-weight: bold;">Opt-Out Period</font>&#8221;). If Metagenomi exercises the
                Opt-Out Right for a Co-Co Program during the applicable Opt-Out Period pursuant to this <u>Section 5.4</u> (Metagenomi Opt-Out), then from and after the date that is the later of (a) [***] or (b) [***] (the &#8220;<font style="font-weight: bold;">Opt-Out Date</font>&#8221;), (i) the applicable Co-Development and Co- Commercialization Agreement will terminate and Ionis will have sole control over, and sole decision-making authority with respect to, at its cost and expense, the
                Development, Commercialization, and other Exploitation of the Licensed Products under such Drug Discovery Program, (ii) the Licensed Products under such Drug Discovery Program will be deemed to be &#8220;Ionis Products&#8221; and such Drug Discovery
                Program will be deemed to be an &#8220;Ionis Program&#8221;, in each case, from and after the Opt-Out Date, (iii) [***], (iv) Ionis will [***], and (v) Metagenomi will [***].</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">21</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="Article_6__Development_and_Commercializa"></a><a name="z_bookmark64"></a>Article 6</div>
      <div style="text-align: center; font-weight: bold;">Development and Commercialization of the Ionis Products</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze1ed0ea1ac0741a7841b16b44e5ee607" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250024"></a><font style="font-weight: bold;">6.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Development</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4b585802cf4345b1a30c03948bacf99f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z6.1.1._General._On_an_Ionis_Program-by-I"></a><font style="font-weight: bold;">6.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">General</font>. On an Ionis Program-by-Ionis Program basis, from and after expiration of the Drug Discovery Term for an Ionis Product, Ionis will have sole control over, and
                sole decision-making authority with respect to, at its cost and expense, the Development of, and the performance of all Medical Affairs with respect to, such Ionis Product in the Field in the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdbbd254de8b1414b934a389383a2376b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z6.1.2._Reporting_for_the_Ionis_Products."></a><font style="font-weight: bold;">6.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Reporting for the Ionis Products</font>. On an Ionis Program-by-Ionis Program basis, during the period after [***], [***] per [***], Ionis will provide Metagenomi with a
                reasonably detailed report regarding the status of Ionis&#8217; Development of the Ionis Products for such Ionis Program. At Metagenomi&#8217;s reasonable request, no more than [***] per [***], the Parties will meet to discuss the Development of the
                Ionis Products.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcd7476f803104d68b2a85d1b929ca085" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z6.1.3._Development_Diligence_for_the_Ion"></a><font style="font-weight: bold;">6.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Development Diligence for the Ionis Products</font>. Ionis (acting directly or through one or more Affiliates or Sublicensees) will use Commercially Reasonable Efforts to
                Develop and seek Regulatory Approval for [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7b6bb298fe4747389291df8183f89d1e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250023"></a><font style="font-weight: bold;">6.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Commercialization</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z468f88b088244a3a9ab70a6a33c3910e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z6.2.1._General._Ionis_will_have_sole_con"></a><font style="font-weight: bold;">6.2.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">General</font>. Ionis will have sole control over, and sole decision-making authority with respect to, at its cost and expense, the Commercialization of the Ionis Products in
                the Field in the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb8bfdece3e7244148917d5ed74b05165" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z6.2.2._Commercialization_Diligence_for_t"></a><font style="font-weight: bold;">6.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Commercialization Diligence for the Ionis Products</font>. Following receipt by or on behalf of Ionis of Regulatory Approval for an Ionis Product in a country, Ionis (acting
                directly or through one or more Affiliates or Sublicensees) will use Commercially Reasonable Efforts to Commercialize such Ionis Product in such country.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_TOC_250022"></a>Article 7</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark65"></a>Regulatory Affairs</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc1c160b5e2414690a4641fab5b17c967" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z7.1._Regulatory_Responsibility._From_and"></a><a name="z_bookmark66"></a><font style="font-weight: bold;">7.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Regulatory Responsibility</font><font style="font-size: 12pt;">. </font>From and after the Effective Date, as between the Parties, Ionis will be responsible for the
                preparation and submission of all Regulatory Submissions (including all meetings with Regulatory Authorities in connection with the same) for all Licensed Products, but, for clarity, not including Regulatory Submissions that relate to
                proprietary Metagenomi components of Licensed Products to which Ionis will have a right of reference pursuant to <u>Section </u><u>7.2</u> (Right of Reference), [***]; <font style="font-style: italic;">provided </font>that Metagenomi
                will assist Ionis or any of its Affiliates or Sublicensees in its efforts to prepare and submit any such Regulatory Submissions in accordance with this <u>Article 7</u> (Regulatory Affairs). Ionis or any of its Affiliates or Sublicensees
                may file all such applications in its own name (or in the name of its designee) and will own and control all such applications. On a Drug Discovery Program-by-Drug Discovery Program basis, at Ionis&#8217; request at any time after a Development
                Candidate is selected for a Drug Discovery Program, the JSC will discuss a high-level regulatory strategy for such Drug Discovery Program (&#8220;<font style="font-weight: bold;">Regulatory Strategy</font>&#8221;), which strategy will leverage
                Metagenomi&#8217;s expertise with Regulatory Submissions for products that are similar to the Licensed Product. For clarity, the JSC will not have any approval rights with respect to the Regulatory Strategy for any Drug Discovery Program and
                Ionis will have sole control over, and sole decision-making authority with respect to, the Regulatory Submissions for the Licensed Products. Notwithstanding the foregoing, if Metagenomi exercises the Co-Co Option for one or more Drug
                Discovery Programs in accordance with <u>Section 5.1</u> (Co-Development and Co-Commercialization Options), then all Regulatory Submissions with respect to any Co-Co Product will be prepared in accordance with the terms set forth in the
                applicable Co-Development and Co-Commercialization Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">22</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z4e72a0e44b8249d4acb0500c9fc66db2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark67"></a><a name="z_TOC_250021"></a><font style="font-weight: bold;">7.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Right of Reference</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb3b88f0cb41d473ea3b330973814d0e3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z7.2.1._Grant._Metagenomi_will_grant_and"></a><font style="font-weight: bold;">7.2.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Grant</font>. Metagenomi will grant, and hereby does grant, to Ionis and its Affiliates and Sublicensees a &#8220;Right of Reference,&#8221; as that term is defined in 21 C.F.R. &#167;
                314.3(b) (or any successor rule or analogous Applicable Law recognized outside of the United States), to all Regulatory Submissions (including any drug master files) submitted by or on behalf of and Controlled by Metagenomi or any of its
                Affiliates that are necessary or reasonably useful to support any Regulatory Submissions for a Licensed Product to be made by Ionis, its Affiliates, or Sublicensees in the Field in the Territory.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcb979da56a5a487388d2046d93efc973" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z7.2.2._Assistance_Cooperation._Ionis_an"></a><a name="z_bookmark68"></a><font style="font-weight: bold;">7.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Assistance; Cooperation</font>. Ionis and its Affiliates and Sublicensees may use such right of reference solely for the purpose of seeking, obtaining, supporting, and
                maintaining Regulatory Approval for the Licensed Products in the Field in the Territory. Metagenomi will use Commercially Reasonable Efforts to take such actions as may be reasonably requested by Ionis to give effect to the intent of this <u>Section


                  7.2</u> (Right of Reference), including, if requested by Ionis, (a) [***], and (b) [***]. [***] incurred by Metagenomi in performing any activities requested by Ionis pursuant to this <u>Section 7.2.2</u> (Assistance; Cooperation) will
                be reimbursed in accordance with <u>Section 3.4.4</u> (Costs of Support).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb837689143e24dc994dd6d0a3898ee39" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark69"></a><a name="z_TOC_250020"></a><font style="font-weight: bold;">7.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Regulatory Support</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf43e7db3b66642d49955f0276d2e8fb1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z7.3.1._Access_to_Data._Metagenomi_will_u"></a><font style="font-weight: bold;">7.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Access to Data</font>. Metagenomi will use Commercially Reasonable Efforts to assist Ionis or any of its Affiliates or Sublicensees in its efforts to prepare and submit any
                Regulatory Submissions to obtain, support, or maintain Regulatory Approvals for all Licensed Products in the Field in the Territory, including by providing Ionis with all data, written reports, and other documentation generated by or on
                behalf of Metagenomi under the Drug Discovery Programs that is necessary or reasonably useful to support any Regulatory Submissions for a Licensed Product, as well as any necessary samples and materials. Unless otherwise noted in the
                Development Supply Agreement or the Commercial Supply Agreement, the costs of Metagenomi providing such support will be reimbursed in accordance with <u>Section 3.4.4</u> (Costs of Support).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z71c345ffa3d34ad1b3f168dea3fe670e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z7.3.2._Review_of_Regulatory_Submissions."></a><font style="font-weight: bold;">7.3.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Review of Regulatory Submissions</font>. Ionis may (but, for clarity, is not required to) provide drafts of any INDs or other Regulatory Submissions for the Licensed Products
                to Metagenomi prior to submission to the applicable Regulatory Authority for Metagenomi to review and provide comments. Metagenomi will use Commercially Reasonable Efforts to review and provide any such requested comments in a timely manner
                and the costs of such support will be reimbursed in accordance with <u>Section 3.4.4</u> (Costs of Support).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">23</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="z_TOC_250019"></a>Article 8</div>
      <div style="text-align: center; font-weight: bold;">Manufacturing</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z84a7d4677030412e948b7dd4e8a9894c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250018"></a><font style="font-weight: bold;">8.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Metagenomi Manufacturing Responsibilities</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z626bfa1991c34f438583ab51294c38d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z8.1.1._Metagenomi_Supply_Term._Subject_t"></a><font style="font-weight: bold;">8.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Supply Term</font>. Subject to <u>Section 8.4</u> (Ionis&#8217; Assumption of Manufacturing Responsibilities), on a Drug Discovery Program-by-Drug Discovery Program
                basis, commencing on [***] and continuing until [***], or such other period as mutually agreed upon by the Parties (the &#8220;<font style="font-weight: bold;">Metagenomi Supply Term</font>&#8221;), Metagenomi will Manufacture (a) [***] (collectively,
                the &#8220;<font style="font-weight: bold;">MG Manufactured Components</font>&#8221;), in each case, that are needed by Ionis for use in its Development activities pursuant to the terms of a development supply agreement (the &#8220;<font style="font-weight: bold;">Development Supply Agreement</font>&#8221;) to be entered into between the Parties and (b) [***] MG Manufactured Components needed by Ionis for use in its Commercialization activities pursuant to the terms of a commercial supply
                agreement (the &#8220;<font style="font-weight: bold;">Commercial Supply Agreement</font>&#8221;) to be entered into between the Parties. Under the Development Supply Agreement and the Commercial Supply Agreement, Metagenomi will provide the MG
                Manufactured Components at [***] (the &#8220;<font style="font-weight: bold;">Supply Price</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z0918c5a4dbb845d3a979215ecfd07c4a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z8.1.2._Requested_CMO._If_Metagenomi_is_"></a><a name="z_bookmark70"></a><font style="font-weight: bold;">8.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Requested CMO</font>. If Metagenomi is, at any point during the Metagenomi Supply Term, Manufacturing any MG Manufactured Components without engaging a CMO, then Ionis may,
                upon written notice to Metagenomi, require Metagenomi to engage a CMO mutually agreeable to the Parties to conduct Manufacturing under this Agreement (such CMO, the &#8220;<font style="font-weight: bold;">Requested CMO</font>&#8221;). Within [***] of
                Metagenomi&#8217;s receipt of such notice requesting Metagenomi engage a Requested CMO, Metagenomi will in good faith negotiate and enter into a written agreement with such Requested CMO for the purposes of Manufacturing the MG Manufactured
                Components (such agreement, the &#8220;<font style="font-weight: bold;">Requested CMO Contract</font>&#8221;) and conduct a transfer of the Manufacturing Know-How to such Requested CMO and otherwise facilitate implementation of such Manufacturing
                Know-How, in each case, in a manner consistent with Metagenomi&#8217;s rights and obligations with respect to the Manufacturing Technology Transfer described in <u>Section 8.5 </u>(Manufacturing After the Metagenomi Supply Term). Metagenomi
                will ensure that the Requested CMO Contract is expressly and freely assignable to and assumable by Ionis without the consent of the Requested CMO. Metagenomi will provide a draft of the Requested CMO Contract to Ionis prior to executing
                such Requested CMO Contract for review and comment and will incorporate Ionis&#8217; reasonable comments. If Metagenomi does not engage the Requested CMO within [***] of its receipt of notice requiring the engagement of such Requested CMO, then
                Ionis may terminate the Metagenomi Supply Term and assume all Manufacturing responsibilities for the MG Manufactured Components.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z49a98db3d6f54ab59e4b798772db9ff0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z8.2._Development_Supply_Agreement._At_su"></a><a name="z_bookmark71"></a><font style="font-weight: bold;">8.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Development Supply Agreement</font>. At such time as directed by the JSC, the Parties will negotiate in good faith the terms of the Development Supply Agreement, and a related
                quality agreement, which agreements will govern the terms and conditions of the Manufacturing of the MG Manufactured Components for Development purposes; <font style="font-style: italic;">provided </font>that if Ionis needs any MG
                Manufactured Components for its Development activities prior to the Parties entering into the Development Supply Agreement, then Metagenomi will supply such MG Manufactured Components on a per-batch basis and Ionis will pay Metagenomi on a
                per-batch basis at the Supply Price for each such batch. The Development Supply Agreement and the related quality agreement will include terms and conditions consistent with the principles set forth on <u>Schedule 8.2</u> (Development
                Supply Agreement Key Terms).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">24</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z516c323c82ca453eb89cb8e71b826853" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z8.3._Commercial_Supply_Agreement._At_suc"></a><font style="font-weight: bold;">8.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Commercial Supply Agreement</font>. At such time as directed by the JSC, the Parties will negotiate in good faith the terms of the Commercial Supply Agreement, and a related
                quality agreement, which agreements will govern the terms and conditions of the Manufacturing of the MG Manufactured Components for Commercialization purposes. The Commercial Supply Agreement and the related quality agreement will include
                terms and conditions consistent with the principles set forth on <u>Schedule 8.2</u> (Development Supply Agreement Key Terms), with such modifications that are reasonable and appropriate for a commercial supply.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z80b2b0cde3df42a7b5e049d5b6658afb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z8.4._Ionis_Assumption_of_Manufacturing_"></a><a name="z_bookmark72"></a><font style="font-weight: bold;">8.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;">[***] <font style="font-weight: bold;">Manufacturing Responsibilities</font>. If, (a) [***], or (b) [***], then, in either case, [***]. For clarity, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z865a6ac4693e43318ad3c209a259aa06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z8.5._Manufacturing_After_the_Metagenomi_"></a><a name="z_bookmark73"></a><font style="font-weight: bold;">8.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Manufacturing After the Metagenomi Supply Term</font>. If Ionis assumes all Manufacturing responsibilities for the MG Manufactured Components [***] or the Metagenomi Supply
                Term otherwise expires, then from and after such date, Ionis will have sole control over and sole decision-making authority with respect to, at its cost and expense, all Manufacturing activities for the MG Manufactured Components; <font style="font-style: italic;">provided </font>that, at Ionis&#8217; request, Metagenomi will continue to Manufacture and supply MG Manufactured Components to Ionis pursuant to the Development Supply Agreement or Commercial Supply Agreement (as
                applicable) until the earlier of [***] or [***]. Promptly upon Ionis&#8217; request after expiration of the Metagenomi Supply Term, Metagenomi will, if and as requested, assign the Requested CMO Contract to Ionis and effect a transfer to Ionis or
                its designee(s) (which designee may be an Affiliate or a Third Party manufacturer, and which Third Party manufacturer may be a primary, backup, or second manufacturer of such MG Manufactured Component) of all Licensed Know-How that is
                necessary or reasonably useful to enable the Manufacture of each MG Manufactured Component (the &#8220;<font style="font-weight: bold;">Manufacturing Know-How</font>&#8221;) and to facilitate implementation of the Manufacturing Know-How at facilities
                designated by Ionis (such transfer and implementation, as more fully described in this <u>Section 8.5</u> (Manufacturing After the Metagenomi Supply Period), the &#8220;<font style="font-weight: bold;">Manufacturing Technology Transfer</font>&#8221;).
                Metagenomi will provide all reasonable assistance requested by Ionis to enable Ionis (or its Affiliate or designated Third Party manufacturer, as applicable) to implement the Manufacturing Know-How at the facilities designated by Ionis. If
                reasonably requested by Ionis, such assistance will include [***]. Without limiting the foregoing, in connection with the Manufacturing Technology Transfer, Metagenomi will cause all appropriate employees and representatives of Metagenomi
                and its Affiliates to meet with employees or representatives of Ionis (or its Affiliate or designated Third Party manufacturer, as applicable) at the applicable manufacturing facility at mutually convenient times to assist with the working
                up and use of the Manufacturing Know-How and with the training of the personnel of Ionis (or its Affiliate or designated Third Party manufacturer(s), as applicable) to the extent reasonably necessary to enable Ionis (or its Affiliate or
                designated Third Party manufacturer(s), as applicable) to use and practice the Manufacturing Know-How. Each Party will be responsible for its own costs and expenses incurred in conducting the Manufacturing Technology Transfer.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark74"></a><a name="z_bookmark75"></a><a name="z_TOC_250017"></a>Article 9</div>
      <div style="text-align: center; font-weight: bold;">Consideration; Financial Terms</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zef783cf00c4d4254ac3eab8ee6effefe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.1._Upfront_Payment._Ionis_will_pay_Met"></a><font style="font-weight: bold;">9.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Upfront Payment</font>. Ionis will pay Metagenomi a one-time upfront payment of $80,000,000 (the &#8220;<font style="font-weight: bold;">Upfront Payment</font>&#8221;) no later than [***] after the Effective Date.
                The Upfront Payment is non- creditable and non-refundable.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">25</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf0b3ab39cceb403193cd6ce4aa29682e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.2._Wave_2_Target_Selection_Fee._On_a_W"></a><a name="z_bookmark76"></a><font style="font-weight: bold;">9.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;">[***]. On a [***] Target-by-[***] Target basis, promptly following [***] in accordance with <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available), Metagenomi will invoice Ionis for the
                applicable amount set forth in <u>Table 9.2</u>, which amount will be based on [***] (each such payment, a &#8220;[***]&#8221;). Ionis will pay such [***] no later than [***] after receipt of such invoice. For clarity, each [***] is only payable once
                for each [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" id="za1f6f969153a4e24931bae6c7b362b81" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 100%; vertical-align: top; background-color: rgb(255, 255, 255); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;"><a name="Wave_2_Target_Selection_Scenario"></a><u>Table 9.2</u> &#8211; [***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 71.18%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">[***]</div>
              </td>
              <td style="width: 28.82%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;"><a name="Wave_2_Target_Selection_Fee"></a>[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 71.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="margin-left: 0.2pt;">[***]</div>
              </td>
              <td style="width: 28.82%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: right; margin-right: 29.05pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 71.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify; margin-left: 0.2pt;"><a name="Scenario_2:_If_the_Wave_2_Target_is_a_ta"></a>[***]</div>
              </td>
              <td style="width: 28.82%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: right; margin-right: 29.05pt;"><a name="z30000000"></a>$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 71.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: justify; margin-left: 0.2pt;"><a name="Scenario_3:_If_the_Wave_2_Target_is_a_ta"></a>[***]</div>
              </td>
              <td style="width: 28.82%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: right; margin-right: 29.05pt;"><a name="z15000000"></a>$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 90pt;"><a name="In_order_for_Scenario_2_of_Table_9.2_to_"></a>In order for [***] of <u>Table 9.2</u> to apply, Metagenomi must (a) [***] and (b) [***].</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdc267cf974f844b1a873eecf4ad940ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.3._Option_Exercise_Fee._On_a_Drug_Disc"></a><a name="z_bookmark77"></a><font style="font-weight: bold;">9.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Option Exercise Fee</font>. On a Drug Discovery Program-by-Drug Discovery Program basis, if Metagenomi exercises a Co-Co Option for a Drug Discovery Program during the
                applicable Co- Co Option Period in accordance with <u>Section 5.1.3</u> (Option Exercise), then Metagenomi will [***] in accordance with the terms set forth in this <u>Section 9.3</u> (Option Exercise Fee), [***] (such amount, the &#8220;<font style="font-weight: bold;">Option Exercise Fee</font>&#8221; for such Drug Discovery Program). No later than [***] after the date on which Metagenomi exercises a Co-Co Option for a Drug Discovery Program, each Party will [***], Ionis will
                invoice Metagenomi for the Option Exercise Fee [***] and Metagenomi will pay the Option Exercise Fee no later than [***] after receipt of Ionis&#8217; invoice.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc91b1d3ece534db1a16b98d718f9416d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark78"></a><a name="z_TOC_250016"></a><font style="font-weight: bold;">9.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis Product Milestone Payments</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2e7940b28a1448a697f25ca6074857fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.4.1._Ionis_Product_Development_Milesto"></a><a name="z_bookmark79"></a><font style="font-weight: bold;">9.4.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Product Development Milestone Payments</font>. Subject to the terms and conditions of this Agreement, including <u>Section 9.5</u> (Ionis Products for [***] Target
                Populations), (a)&#160; with respect to the [***] set forth below, on an Ionis Program-by-Ionis Program basis and (b) with respect to the [***] set forth below, on an Ionis Product-by-Ionis Product basis, Ionis will pay one-time milestone
                payments to Metagenomi of the amounts set forth in <u>Table 9.4.1</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product Development Milestone Payment</font>&#8221;) upon the first achievement by Ionis or any of its Affiliates or
                Sublicensees of each of the development milestone events set forth in <u>Table 9.4.1</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product Development Milestone Event</font>&#8221;) for each Ionis Program or Ionis Product (as
                applicable); <font style="font-style: italic;">provided </font>that, with respect to the [***] set forth below, on an Ionis Program-by-Ionis Program basis, if more than one Ionis Product for the same Ionis Program achieve an Ionis Product
                Development Milestone Event, then [***].&#160; Each Ionis Product Development Milestone Payment is payable only once for each Ionis Program or Ionis Product (as applicable), regardless of the number of times the corresponding Ionis Product
                Development Milestone Event is achieved for such Ionis Program or Ionis Product (as applicable). If Ionis or its Affiliates or Sublicensees achieve all of the Ionis Product Development Milestone Events for an Ionis Product, then the Ionis
                Product Development Milestone Payments payable by Ionis under this <u>Section 9.4.1</u> (Ionis Product Development Milestone Payments) for such Ionis Product will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">26</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" border="0" align="center" id="zd82f9290a6aa48888fd0f0166462ea4b" style="border-collapse: collapse; width: 100%; color: #000000; font-family: 'Times New Roman'; font-size: 10pt; text-align: left;">

            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); font-weight: bold;" colspan="2">
                <div style="text-align: center;"><u>Table 9.4.1</u> &#8211; Ionis Product Development Milestones</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); color: rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Ionis Product Development </div>
                <div style="text-align: center; font-weight: bold;">Milestone Event</div>
              </td>
              <td style="width: 50%; vertical-align: middle; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center; font-weight: bold;">
                <div>Ionis Product Development Milestone Payment</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>1. [***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 6.3pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>2. [***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 6.3pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>3. [***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 6.2pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z55e1bd84d710434ca4263428ed8e0967" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.4.2._Ionis_Product_Regulatory_Mileston"></a><a name="z_bookmark80"></a><font style="font-weight: bold;">9.4.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Product Regulatory Milestone Payments</font>. Subject to the terms and conditions of this Agreement, including <u>Section 9.5</u> (Ionis Products for [***] Target
                Populations), on an Ionis Product-by-Ionis Product basis, Ionis will pay one-time milestone payments to Metagenomi of the amounts set forth in <u>Table 9.4.2</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product Regulatory
                  Milestone Payment</font>&#8221;) upon the first achievement by Ionis or any its Affiliates or Sublicensees of each of the regulatory milestone events set forth in <u>Table 9.4.2</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product
                  Regulatory Milestone Event</font>&#8221;) by an Ionis Product. Each Ionis Product Regulatory Milestone Payment is payable only once for each Ionis Product, regardless of the number of times the corresponding Ionis Product Regulatory Milestone
                Event is achieved for an Ionis Product. If Ionis or its Affiliates or Sublicensees achieve all of the Ionis Product Regulatory Milestone Events for an Ionis Product, then the Ionis Product Regulatory Milestone Payments payable by Ionis
                under this <u>Section 9.4.2</u> (Ionis Product Regulatory Milestone Payments) for such Ionis Product will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" align="center" id="z9f25628b4f224beb84c03e955e3fc723" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;">Table 9.4.2 &#8211; Ionis Product Regulatory Milestones</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); font-weight: bold;">
                <div style="text-align: center;">Ionis Product Regulatory </div>
                <div style="text-align: center;">Milestone Event</div>
              </td>
              <td style="width: 50%; vertical-align: middle; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;">
                <div style="font-weight: bold;">Ionis Product Regulatory Milestone Payment</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>1. [***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 49%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: justify;">2. [***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 6.2pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">27</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za251d358f10c42359f5e990f14905a6a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.4.3._Ionis_Product_Sales_Milestone_Pay"></a><a name="z_bookmark81"></a><font style="font-weight: bold;">9.4.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Product Sales Milestone Payments</font>. Subject to the terms and conditions of this Agreement, including <u>Section 9.5</u> (Ionis Products for [***] Target
                Populations), on an Ionis Product-by-Ionis Product basis, Ionis will pay one-time milestone payments to Metagenomi of the amounts set forth in <u>Table 9.4.3</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product Sales Milestone
                  Payment</font>&#8221;) upon the first achievement by Ionis or any of its Affiliates or Sublicensees of each of the sales milestone events set forth in <u>Table 9.4.3</u> (each, an &#8220;<font style="font-weight: bold;">Ionis Product Sales Milestone
                  Event</font>&#8221;) for an Ionis Product. Each Ionis Product Sales Milestone Payment is payable only once for each Ionis Product, regardless of the number of times the corresponding Ionis Product Sales Milestone Event is achieved for an Ionis
                Product. If Ionis or its Affiliates or Sublicensees achieve all of the Ionis Product Sales Milestone Events for an Ionis Product, then the Ionis Product Sales Milestone Payments payable by Ionis under this <u>Section 9.4.3</u> (Ionis
                Product Sales Milestone Payments) for such Ionis Product will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" border="0" align="center" id="zb09c59c829834a2dbba6d0f218e0f3b1" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); text-align: center;" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); width: 1%;" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;"><u>Table 9.4.3</u> &#8211; Ionis Product Sales Milestones</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); text-align: center;" colspan="1">&#160;</td>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 48%; vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Ionis Product Sales Milestone Event</div>
              </td>
              <td style="width: 50%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Ionis Product Sales Milestone Payment</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 1%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">1.</td>
              <td style="width: 48%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>The first Calendar Year in which the aggregate Net Sales for an Ionis Product exceed $[***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 11.15pt; margin-left: 11.6pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 1%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">2.</td>
              <td style="width: 48%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>The first Calendar Year in which the aggregate Net Sales for an Ionis Product exceed $[***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 11.15pt; margin-left: 11.6pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 1%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">3.</td>
              <td style="width: 48%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>The first Calendar Year in which the aggregate Net Sales for an Ionis Product exceed $[***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 11.15pt; margin-left: 11.6pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 1%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">4.</td>
              <td style="width: 48%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>The first Calendar Year in which the aggregate Net Sales for an Ionis Product exceed $[***]</div>
              </td>
              <td style="width: 50%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 11.15pt; margin-left: 11.6pt;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z47f9faba90784f5d8a629447c4f7a9fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.4.4._Notice_Payment_Skipped_Mileston"></a><font style="font-weight: bold;">9.4.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Notice; Payment; Skipped Milestones</font>. Ionis will provide Metagenomi with written notice upon the achievement of each Ionis Product Development Milestone Event, Ionis
                Product Regulatory Milestone Event, and Ionis Product Sales Milestone Event, such written notice to be provided (a) with respect to any Ionis Product Development Milestone Event or Ionis Product Regulatory Milestone Event within [***] after
                such achievement and (b) with respect to any Ionis Product Sales Milestone Event, on or prior to the date of delivery of the Ionis Royalty Report under <u>Section 9.6.4</u> (Ionis Royalty Reports) for the Calendar Year in which such
                milestone event is first achieved. Following receipt of such written notice, Metagenomi will promptly invoice Ionis for the applicable milestone payment and Ionis will make the appropriate milestone payment within [***] after receipt of
                such invoice; <font style="font-style: italic;">provided </font>that with respect to the first Ionis Product Development Milestone Event (for selection of the first Development Candidate for an Ionis Program), Metagenomi may only invoice
                Ionis after [***], and Ionis will have no obligation to make any payment with respect to such Ionis Product Development Milestone Event unless [***] and Metagenomi provides Ionis with an invoice for the applicable amount. Each Ionis Product
                Development Milestone Event is intended to be successive. If any Ionis Product Development Milestone Event does not occur with respect to an Ionis Product for an Ionis Program, then such skipped milestone event will be deemed to have been
                achieved upon the achievement of the next successive milestone event with respect to an Ionis Product for such Ionis Program. Payment for any such skipped milestone that is owed in accordance with the provisions of the foregoing sentence
                will be due concurrently with the payment for the next successive Ionis Product Development Milestone Event. If more than one Ionis Product Sales Milestone Event occurs with respect to an Ionis Product in the same Calendar Year, then
                payments with respect to all applicable Ionis Product Sales Milestone Events will be paid for such Calendar Year.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">28</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z3149d3a21ff34c679e9c4c23201f27b2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.5._Ionis_Products_for_Ultra-Rare_Targe"></a><a name="z_bookmark82"></a><font style="font-weight: bold;">9.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Products for </font>[***] <font style="font-weight: bold;">Target Populations</font>. If an Ionis Product is intended to treat target populations with [***] (each such
                population, [***] &#8220;[***] <font style="font-weight: bold;">Target Population</font>&#8221;), then Ionis will notify Metagenomi and [***], in each case, for such Ionis Product, which [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zda81fa733e5043aaa74d6e143a4a5b2c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark83"></a><a name="z_TOC_250015"></a><font style="font-weight: bold;">9.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis Product Royalty Payments</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8760b199fd8c43d489a42654e2e60847" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.6.1._Ionis_Royalty_Rates._Subject_to_t"></a><a name="z_bookmark84"></a><font style="font-weight: bold;">9.6.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Royalty Rates</font>. Subject to the terms and conditions of this Agreement, including the provisions of <u>Section 9.6.2</u>. (Adjustments to Ionis Royalties), on an
                Ionis Product-by-Ionis Product basis, Ionis will pay Metagenomi royalties based on the aggregate Annual Net Sales of each Ionis Product at the rates set forth in <u>Table 9.6.1</u>. On an Ionis Product-by- Ionis Product and
                country-by-county basis such royalties will be payable until the expiration of the applicable Royalty Term for each Ionis Product in such country. The royalty payments made pursuant to this <u>Section 9.6.1</u> (Ionis Royalty Rates), the &#8220;<font style="font-weight: bold;">Ionis Royalties</font>&#8221; and the rates set forth in <u>Table 9.6.1</u>, the &#8220;<font style="font-weight: bold;">Ionis Royalty Rates</font>.&#8221;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" id="z6cae3b28efd94448bc42f7c62fc22714" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;"><u>Table 9.6.1</u> &#8211; Royalty Rates for Ionis Products</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 84.03%; vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); font-weight: bold;">
                <div style="text-align: center;">&#160;</div>
                <div style="text-align: center;">&#160;</div>
                <div style="text-align: center;">Annual Net Sales of an Ionis Product in the Territory</div>
              </td>
              <td style="width: 15.97%; vertical-align: top; background-color: rgb(255, 255, 255); border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); font-weight: bold;">
                <div style="text-align: center;">Royalty </div>
                <div style="text-align: center;">Rate as a </div>
                <div style="text-align: center;">Percentage</div>
                <div style="text-align: center;">of Net </div>
                <div style="text-align: center;">Sales</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 84.03%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>Portion of Annual Net Sales of each Ionis Product that is less than or equal to $[***]</div>
              </td>
              <td style="width: 15.97%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 84.03%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>Portion of Annual Net Sales of each Ionis Product that is greater than $[***], and less than or equal to $[***]</div>
              </td>
              <td style="width: 15.97%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 84.03%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>Portion of Annual Net Sales for each Ionis Product that is greater than $[***], and less than or equal to $[***]</div>
              </td>
              <td style="width: 15.97%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 84.03%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>Portion of Annual Net Sales of each Ionis Product that is greater than $[***]</div>
              </td>
              <td style="width: 15.97%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">[***]%</div>
              </td>
            </tr>

        </table>
      </div>
      <div>&#160;</div>
      <div style="margin: 0px 0px 0px 86.95pt; text-align: justify;"><a name="By_way_of_example_only_if_the_Annual_Ne"></a>By way of example only, if the Annual Net Sales for an Ionis Product are $[***] for a given Calendar Year, then the Ionis Royalties
        payable with respect to such Annual Net Sales for such Ionis Product in such Calendar Year, subject to adjustment as set forth in <u>Section 9.6.2</u> (Adjustment to Ionis Royalties) would be: [***].&#160; For the avoidance of doubt, the obligation to
        pay Ionis Royalties will be imposed only once with respect to the same unit of an Ionis Product.</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z95881e1d770f4a338c41b76b50999501" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.6.2._Adjustments_to_Ionis_Royalties."></a><a name="z_bookmark85"></a><font style="font-weight: bold;">9.6.2.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Adjustments to Ionis Royalties</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z987b4563e53e495f8f8b4ea0825978d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Expiration_of_Valid_Claims._Subject_"></a><a name="z_bookmark86"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Expiration of Valid Claims</font>. Subject to <u>Section 9.6.3</u> (Cumulative Effect of Ionis Royalty Reductions), on an Ionis Product-by-Ionis Product and country-by-
                country basis in the Territory, if during the Royalty Term for an Ionis Product in a given country there is no Valid Claim of a Royalty Bearing Patent Right Covering such Ionis Product in such country, then commencing in the first Calendar
                Quarter after the date on which this <u>Section 9.6.2(a)</u> (Expiration of Valid Claims) applies and for the remainder of the Royalty Term for such Ionis Product in such country, the Annual Net Sales for such Ionis Product in such country
                will be reduced by [***]% for purposes of calculating the Ionis Royalties owed under <u>Section 9.6.1</u> (Ionis Royalty Rates).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">29</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf88057ef76b342fc84ce4e3b2b277693" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Biosimilar_Product._Subject_to_Secti"></a><a name="z_bookmark87"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Biosimilar Product</font>. Subject to <u>Section 9.6.3</u> (Cumulative Effect of Ionis Royalty Reductions), if, on an Ionis Product-by-Ionis Product and country-by-country
                basis, a Biosimilar Product with respect to an Ionis Product is approved for sale in a country, then commencing in the Calendar Quarter in which such approval was obtained and continuing for the remainder of the Royalty Term for such Ionis
                Product in such country, the Annual Net Sales for such Ionis Product in such country will be reduced by [***]% for purposes of calculating the Ionis Royalties owed under <u>Section 9.6.1</u> (Ionis Royalty Rates).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z921f169f683240ee963912e48ea3c7d7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Third_Party_Payments._Subject_to_Sec"></a><a name="z_bookmark88"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Third Party Payments</font><font style="font-style: italic;">. </font>Subject to <u>Section 9.6.3</u> (Cumulative Effect of Ionis Royalty Reductions), Ionis will be entitled
                to credit against the Ionis Royalties due to Metagenomi in a given Calendar Quarter [***]% of (i) [***] that are actually paid by Ionis or any of its Affiliates or Sublicensees to any Third Party in consideration for rights under any Patent
                Right, Know-How, or other intellectual property owned or controlled by such Third Party (whether by acquisition or license) (such rights, &#8220;<font style="font-weight: bold;">Third Party IP</font>&#8221;) that is acquired or licensed by Ionis or any
                of its Affiliates or Sublicensees after the Effective Date, and [***] for Ionis or any of its Affiliates or Sublicensees to Exploit a Development Candidate as such Development Candidate exists as of the date of expiration of the Drug
                Discovery Term for the applicable Drug Discovery Program, and (ii) [***] (such amount in (i) or (ii), the &#8220;<font style="font-weight: bold;">Third Party Payment</font>&#8221;). Notwithstanding the foregoing, Third Party Payment shall exclude
                [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z5a1249228d0345828a1ad6de2c29ff87" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.6.3._Cumulative_Effect_of_Ionis_Royalt"></a><a name="z_bookmark89"></a><font style="font-weight: bold;">9.6.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Cumulative Effect of Ionis Royalty Reductions</font>. In no event will the royalty reductions for Ionis Products permitted under <u>Section 9.6.2(a)</u> (Expiration of Valid
                Claims), <u>Section</u>&#160;<u>9.6.2(b)</u> (Biosimilar Product), or <u>Section 9.6.2(c)</u> (Third Party Payments), alone or together, reduce the Ionis Royalties due to Metagenomi for an Ionis Product in a given Calendar Quarter by more than
                [***]% of the applicable Ionis Royalties that would otherwise be owed on the Annual Net Sales of such Ionis Product. If Ionis would, but for the restriction set forth in this <u>Section 9.6.3</u> (Cumulative Effect of Ionis Royalty
                Reductions), have the right to reduce the Ionis Royalties due to Metagenomi by more than [***]%, then [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze2512f88aca44f19a00307c2e49cab57" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.6.4._Ionis_Royalty_Reports._Commencing"></a><font style="font-weight: bold;">9.6.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Royalty Reports</font>. Commencing on the First Commercial Sale of an Ionis Product and for so long as Ionis Royalties are due under this Agreement, no later than (a)
                [***] prior to the start of each Calendar Year, Ionis will deliver a written good faith non-binding estimate to Metagenomi of the projected Net Sales for the upcoming Calendar Year, (b) [***] after the end of each Calendar Quarter, Ionis
                will deliver a written good faith non- binding estimate to Metagenomi of the Net Sales in the relevant Calendar Quarter and the Ionis Royalties payable on such Net Sales, and (c) [***] after the end of each Calendar Quarter, Ionis will
                deliver a written report (each, an &#8220;<font style="font-weight: bold;">Ionis Royalty Report</font>&#8221;) to Metagenomi specifying on an Ionis Product-by-Ionis Product and country-by-country basis: (i) Net Sales in the relevant Calendar Quarter;
                (ii) to the extent such Net Sales include sales not denoted in US Dollars, a summary of the then-current exchange rate methodology(ies) used for the calculation of Net Sales in accordance with <u>Section 9.14</u> (Currency of Payment;
                Non-Refundable Payments); (iii) the Ionis Royalties payable on such Net Sales; and (iv) if applicable, the Ionis Product Sales Milestone Payments owed to Metagenomi in the relevant Calendar Quarter. All Ionis Royalty Reports will be the
                Confidential Information of Ionis. Ionis will pay the Ionis Royalties for each Calendar Quarter no later than [***] after receipt of an invoice from Metagenomi, which invoice will be provided promptly following Metagenomi&#8217;s receipt of each
                Ionis Royalty Report from Ionis pursuant to this <u>Section 9.6.4</u> (Ionis Royalty Reports). For clarity, the submission by Metagenomi of an invoice to Ionis based on an Ionis Royalty Report will be without prejudice to Metagenomi&#8217;s
                right to dispute an Ionis Royalty Report or to audit an Ionis Royalty Report pursuant to <u>Section 9.13</u> (Records and Audits).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">30</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zd0450d34e16143359779daba8bdf67cc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250014"></a><font style="font-weight: bold;">9.7.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Existing In-License Agreements</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z89de7b53a51c46a5815a75e6c9cebf67" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.7.1._Effective_Date_Licensed_Technolog"></a><font style="font-weight: bold;">9.7.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Effective Date Licensed Technology; Existing Metagenomi In-License Agreements</font>. Metagenomi hereby represents and warrants that none of the Licensed Technology Controlled
                by Metagenomi as of the Effective Date is in-licensed or acquired by Metagenomi under agreements with Third Party licensors or sellers. On a Collaboration Target-by-Collaboration Target basis, if any Patent Rights or Know-How, as of the
                date a Proposed Target becoming a Collaboration Target pursuant to <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available), have been acquired or in-licensed by Metagenomi and if solely owned by Metagenomi without any
                encumbrance or restriction on licensing, would constitute Licensed Technology as a result of such Proposed Target becoming a Collaboration Target pursuant to <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available) (any such
                agreement, an &#8220;<font style="font-weight: bold;">Existing Potential Metagenomi In-License Agreement</font>&#8221;), then Metagenomi will, within [***] of the applicable Proposed Target becoming a Collaboration Target, provide Ionis with (a) notice
                and a copy of such Existing Potential Metagenomi In-License Agreements (which may be redacted to exclude provisions thereof that would not be applicable to Ionis as a licensee or sublicensee (as the case may be)), and (b) any disclosures
                that would be made against the representations and warranties in <u>Section 12.2</u> (Additional Representations of Metagenomi) if such Existing Potential Metagenomi In-License Agreements were to become Metagenomi In-License Agreements. If
                Ionis provides written notice, within [***] of receipt of such information from Metagenomi, that it would like to have any such Existing Potential Metagenomi In- License Agreement included in the licenses granted under this Agreement and be
                subject to the terms of such Existing Potential Metagenomi In-License Agreement that are applicable to a licensee or sublicensee (as the case may be) thereunder, then such intellectual property rights described in such notice will
                automatically be deemed included in the Licensed Technology, and such Existing Potential Metagenomi In-License Agreement will be considered a Metagenomi In-License Agreement. Except as otherwise provided in this Agreement, as between the
                Parties, [***] will be responsible for all payments that arise under any license or other agreement to which Metagenomi or its Affiliate is a party, including any Metagenomi In-License Agreement, in connection with this Agreement, including
                with respect to the Development, Manufacture, and Commercialization of Licensed Products.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z19b6d9910dc14c26bd1cc9cec9620287" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.7.2._Existing_Potential_Ionis_In-Licen"></a><font style="font-weight: bold;">9.7.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Existing Potential Ionis In-License Agreements</font>. With respect to any Patent Rights or Know-How that are the subject of an Ionis IP Option and are in-licensed or acquired
                by Ionis from any Third Party as of the applicable Ionis IP Option Effective Date (any such agreement, an &#8220;<font style="font-weight: bold;">Existing Potential Ionis In-License Agreement</font>&#8221;), Ionis will, within [***] of the applicable
                Ionis IP Option Effective Date, provide Metagenomi with notice and a copy of each such Existing Potential Ionis In-License Agreement (which may be redacted to exclude provisions thereof that would not be applicable to Metagenomi as a
                licensee or sublicensee (as the case may be)). If Metagenomi provides written notice, within [***] of receipt of such information from Ionis, that it would like to have any such Existing Potential Ionis In-License Agreement included in the
                licenses granted under this Agreement and be subject to the terms of such Existing Potential Ionis In-License Agreement that are applicable to a licensee or sublicensee (as the case may be) thereunder, then such intellectual property rights
                described in such notice will automatically be deemed included in the Ionis Background Technology and such Existing Potential Ionis In-License Agreement will be considered an Ionis In-License Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">31</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z7206d3e87bb9456b919e7d64feb657bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250013"></a><font style="font-weight: bold;">9.8.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">New In-License Agreements</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zedd3ef5e1f7b439db6af6c2d80014865" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.8.1._Proposed_New_In-License_Agreement"></a><font style="font-weight: bold;">9.8.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Proposed New In-License Agreements</font>. Either Party (an &#8220;<font style="font-weight: bold;">Acquiring Party</font>&#8221;) may, during the Term, acquire or in-license rights to
                additional intellectual property from a Third Party that, if solely owned by such Party, without any encumbrance or restriction on licensing, would constitute Licensed Technology (if such Acquiring Party is Metagenomi) or Ionis Background
                Technology (if such Acquiring Party is Ionis) (any such agreement entered into by Metagenomi, a &#8220;<font style="font-weight: bold;">Proposed New Metagenomi In-License Agreement</font>,&#8221; any such agreement entered into by Ionis, a &#8220;<font style="font-weight: bold;">Proposed New Ionis In-License Agreement</font>,&#8221; and any Proposed New Metagenomi In-License Agreements or Proposed New Ionis In-License Agreements, a &#8220;<font style="font-weight: bold;">Proposed New In-License
                  Agreement</font>&#8221;). Any such Proposed New In- License Agreement will be freely licensable or sublicensable to the non-Acquiring Party to the same extent that Licensed Technology or Ionis Background Technology (as applicable) is licensed
                to the non-Acquiring Party hereunder (including the right to grant sublicenses through multiple tiers) and will not (a) impose any material restrictions or obligations on the non-Acquiring Party as a licensee or sublicensee or (b)
                disadvantage the non-Acquiring Party, in each case ((a) and (b)), as compared to any other potential licensee or sublicensee under such Proposed New In-License Agreement. The Acquiring Party will [***] include in any such Proposed New
                In-License Agreement that is an in-license a provision pursuant to which [***]. Promptly following execution of a Proposed New In-License Agreement, the Acquiring Party will provide the non- Acquiring Party with a copy of such Proposed New
                In-License Agreement (which may be redacted to exclude provisions thereof that would not be applicable to the non-Acquiring Party as a licensee or sublicensee (as the case may be)).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze0649981f4d048368c91f26b53e139b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.8.2._Acceptance_of_a_Proposed_In-Licen"></a><font style="font-weight: bold;">9.8.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Acceptance of a Proposed In-License Agreement</font>. If the non-Acquiring Party provides written notice, within [***] of receipt of a Proposed New In-License Agreement, that
                it would like to have such intellectual property rights included in the licenses granted under this Agreement and be subject to the terms of such Proposed New In-License Agreement that are applicable to a licensee or sublicensee (as the
                case may be) thereunder, then such intellectual property rights described in such notice will automatically be deemed included in the Licensed Technology (if such Acquiring Party is Metagenomi) or Ionis Background Technology (if such
                Acquiring Party is Ionis) (any such Proposed New Metagenomi In- License Agreement with respect to intellectual property rights that are included in the Licensed Technology pursuant to this sentence, a &#8220;<font style="font-weight: bold;">New
                  Metagenomi In-License Agreement</font>,&#8221; any such Proposed New Ionis In-License Agreement with respect to intellectual property rights that are included in the Ionis Background Technology pursuant to this sentence, a &#8220;<font style="font-weight: bold;">New Ionis In-License Agreement</font>&#8221; and any New Metagenomi In- License Agreement or New Ionis In-License Agreement, a &#8220;<font style="font-weight: bold;">New In-License Agreement</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">32</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zcbe5c988372b4de29d555c097a80761c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.9._Payment_Obligations_Under_Certain_I"></a><a name="z_bookmark90"></a><font style="font-weight: bold;">9.9.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Payment Obligations Under Certain In-License Agreements</font>. Any payment obligations arising under the Metagenomi In-License Agreements or the Ionis In-License Agreements
                that are directly a result of the Development, Manufacture, or Commercialization of a Licensed Product or Metagenomi Product (as applicable) in the Field by or on behalf of the non-Acquiring Party or any of its Affiliates or Sublicensees,
                after application of all available reductions to and deductions from such payment obligations under the applicable agreement (but, for the avoidance of doubt, excluding [***]), will be paid by [***] and reimbursed by [***] in accordance
                with this <u>Section 9.9</u> (Payment Obligations Under Certain In-License Agreements), but, with respect to [***], subject to [***] pursuant to <u>Section 9.6.2(c)</u> (Third Party Payments). Except as set forth in the immediately
                preceding sentence, [***] will be responsible for [***] under such agreements (including [***]). [***] will provide [***] with a reasonably detailed invoice for any payments made by [***] under a Metagenomi In-License Agreement or Ionis
                In-License Agreement that are reimbursable by [***] pursuant to this <u>Section 9.9</u> (Payment Obligations Under Certain In-License Agreements) within [***], and [***] will pay the undisputed portion of such invoices within [***] of
                receipt thereof. For clarity, [***] and its Affiliates will be obligated to [***] a given amount owed under a Metagenomi In-License Agreement or Ionis In-License Agreement one time only. Notwithstanding the foregoing, [***] may, in its sole
                discretion, notify [***] that it elects to abandon its payment obligations under this <u>Section 9.9</u> (Payment Obligations Under Certain In-License Agreements) with respect to a Metagenomi In-License Agreement or Ionis In-License
                Agreements, whereupon such agreement will no longer be deemed to be a Metagenomi In-License Agreement or Ionis In-License Agreements under this Agreement (as applicable) and [***] will no longer be responsible for such payment obligations
                from and after the date of such notice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z453ac0d7d43a424a8ef97bdd366165e2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark91"></a><a name="z_TOC_250012"></a><font style="font-weight: bold;">9.10.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Metagenomi Product Economics</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2616efa167ae47c4b054a729c0903b16" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.10.1._Metagenomi_Product_Milestone_Pay"></a><a name="z_bookmark92"></a><font style="font-weight: bold;">9.10.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Product Milestone Payments</font>. If Metagenomi exercises the Ionis IP Option in accordance with <u>Section 2.7</u> (Ionis Proprietary Toolbox of Chemical
                Modifications), then, on a Metagenomi Product-by-Metagenomi Product basis, Metagenomi will pay one- time milestone payments to Ionis of the amounts set forth in <u>Table 9.10.1</u> (each, a &#8220;<font style="font-weight: bold;">Metagenomi
                  Product Milestone Event</font>&#8221;) upon the first achievement by Metagenomi or any of its Affiliates or Sublicensees of each of the milestone events set forth in <u>Table 9.10.1</u> (each, a &#8220;<font style="font-weight: bold;">Metagenomi
                  Product Milestone Payment</font>&#8221;) for a Metagenomi Product. Each Metagenomi Product Milestone Payment is payable only once for each Metagenomi Product, regardless of the number of times the corresponding Metagenomi Product Milestone
                Event is achieved for a Metagenomi Product. If Metagenomi or its Affiliates or Sublicensees achieve all of the Metagenomi Product Milestone Events for a Metagenomi Product, then the Metagenomi Product Milestone Payments payable by
                Metagenomi under this <u>Section 9.10.1</u> (Metagenomi Product Milestone Payments) for such Metagenomi Product will not exceed $[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="margin-left: 90pt;">
        <table cellspacing="0" cellpadding="0" border="0" id="z16836ab22280484b932738601b09ccf3" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); border-top: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;"><u>Table 9.10.1</u> &#8211; Metagenomi Product Milestones</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 40.82%; vertical-align: top; background-color: rgb(255, 255, 255); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Metagenomi Product Milestone Event</div>
              </td>
              <td style="width: 59.18%; vertical-align: top; background-color: rgb(255, 255, 255); border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Metagenomi Product Milestone Payment</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 40.82%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>1. [***]</div>
              </td>
              <td style="width: 59.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 6.2pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 40.82%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>2. [***]</div>
              </td>
              <td style="width: 59.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 6.2pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1">&#160;</td>
              <td style="width: 40.82%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div>3. [***]</div>
              </td>
              <td style="width: 59.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
                <div style="text-align: center; margin-right: 6.2pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>
            <tr>
              <td style="width: 1%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1">&#160;</td>
              <td style="width: 40.82%; vertical-align: top; border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div>4. [***]</div>
              </td>
              <td style="width: 59.18%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; margin-right: 6.3pt; margin-left: 6.65pt;">$[***]</div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">33</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zd72f8a4310694f60bb3330e8c128aaf1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.10.2._Notice_Payment_Skipped_Milesto"></a><font style="font-weight: bold;">9.10.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Notice; Payment; Skipped Milestones</font>. Metagenomi will provide Ionis with written notice upon the achievement of each Metagenomi Product Milestone Event within [***]
                after such achievement and will pay Ionis within [***] after receipt of an invoice from Ionis. Each Metagenomi Product Milestone Event is intended to be successive. If any Metagenomi Product Milestone Event does not occur with respect to a
                Metagenomi Product, then such skipped milestone event will be deemed to have been achieved upon the achievement of the next successive milestone event with respect to such Metagenomi Product; <font style="font-style: italic;">provided </font>that


                the [***] Metagenomi Product Milestone Event shall not be deemed to have been achieved upon the achievement of the [***] Metagenomi Product Milestone Event. Payment for any such skipped milestone that is owed in accordance with the
                provisions of the foregoing sentence will be due concurrently with the payment for the next successive Metagenomi Product Milestone Event.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z881433853aee4c429beb85017ab295ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.10.3._Metagenomi_Royalties."></a><font style="font-weight: bold;">9.10.3.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Metagenomi Royalties</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4a7fed5433c84e1d8c3a9ebe5992f8d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Metagenomi_Royalty_Rates._Subject_to"></a><a name="z_bookmark93"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Royalty Rates</font>. Subject to the terms and conditions of this Agreement, including the provisions of <u>Section 9.10.3(b)</u> (Adjustments to Metagenomi
                Royalties), on a Metagenomi Product-by-Metagenomi Product and country-by-country basis, Metagenomi will pay Ionis an amount equal to [***]% of the Net Sales of the applicable Metagenomi Product in a country in the Territory by Metagenomi
                and its Affiliates and its Sublicensees until the expiration of the applicable Metagenomi Royalty Term for such Metagenomi Product in such country. The royalty payments made pursuant to this <u>Section 9.10.3(a)</u> (Metagenomi Royalty
                Rates), the &#8220;<font style="font-weight: bold;">Metagenomi Royalties</font>&#8221; and the rate set forth in this <u>Section 9.10.3(a)</u> (Metagenomi Royalty Rates), the &#8220;<font style="font-weight: bold;">Metagenomi Royalty Rate</font>.&#8221;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze7fcb595bca24bcdbe40e69cf8f7374d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Adjustment_to_Metagenomi_Royalties._"></a><a name="z_bookmark94"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Adjustment to Metagenomi Royalties</font>. On a Metagenomi Product-by- Metagenomi Product and country-by-country basis in the Territory, if during the Metagenomi Royalty Term
                for a Metagenomi Product in a given country there is no Valid Claim of a Patent Right within the Ionis Background Technology Covering such Metagenomi Product in such country, then commencing in the first Calendar Quarter after the date on
                which this <u>Section 9.10.3(b)</u> (Adjustments to Metagenomi Royalties) applies and for the remainder of the Royalty Term for such Metagenomi Product in such country, the Net Sales for such Metagenomi Product in such country will be
                reduced by [***]% for purposes of calculating the Metagenomi Royalties owed under <u>Section 9.10.3(a)</u> (Metagenomi Royalty Rates).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">34</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z48b4bddbe1fb4ded8c07650ef7a49f09" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.10.4._Metagenomi_Royalty_Reports._Comm"></a><a name="z_bookmark95"></a><font style="font-weight: bold;">9.10.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Royalty Reports</font>. Commencing on the First Commercial Sale (applied <font style="font-style: italic;">mutatis mutandis</font>) of a Metagenomi Product and for
                so long as Metagenomi Royalties are due under this Agreement, no later than (a) [***] prior to the start of each Calendar Year, Metagenomi will deliver a written good faith non-binding estimate to Ionis of the projected Net Sales for the
                upcoming Calendar Year, (b) [***] after the end of each Calendar Quarter, Metagenomi will deliver a written good faith non-binding estimate to Ionis of the Net Sales in the relevant Calendar Quarter and the Metagenomi Royalties payable on
                such Net Sales, and (c) [***] after the end of each Calendar Quarter, Metagenomi will deliver a written report (each, a &#8220;<font style="font-weight: bold;">Metagenomi Royalty Report</font>&#8221;) to Ionis specifying on a Metagenomi
                Product-by-Metagenomi Product and country-by-country basis: (i) Net Sales in the relevant Calendar Quarter; (ii) to the extent such Net Sales include sales not denoted in US Dollars, a summary of the then-current exchange rate
                methodology(ies) used for the calculation of Net Sales in accordance with <u>Section 9.14</u> (Currency of Payment; Non- Refundable Payments); and (iii) the Metagenomi Royalties payable on such Net Sales. All Metagenomi Royalty Reports
                will be the Confidential Information of Metagenomi. Metagenomi will pay the Metagenomi Royalties for each Calendar Quarter no later than [***] after receipt of an invoice from Ionis, which invoice will be provided promptly following Ionis&#8217;
                receipt of each Metagenomi Royalty Report from Metagenomi pursuant to this <u>Section 9.10.4</u> (Metagenomi Royalty Reports). For clarity, the submission by Ionis of an invoice to Metagenomi based on a Metagenomi Royalty Report will be
                without prejudice to Ionis&#8217; right to dispute a Metagenomi Royalty Report or to audit a Metagenomi Royalty Report pursuant to <u>Section 9.13</u> (Records and Audits).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z21537cacc4a448058a3652c0b2f5a656" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.11._Other_Payments._With_respect_to_an"></a><a name="z_bookmark96"></a><font style="font-weight: bold;">9.11.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Other Payments</font>. With respect to any amounts owed under this Agreement by one Party to the other for which no other invoicing and payment procedure is otherwise
                specified in this Agreement, a Party will provide an invoice, together with reasonable supporting documentation, to the other Party for such amounts. The owing Party will pay any undisputed amounts within [***] of receipt of the invoice,
                and any disputed amounts owed by a Party will be paid within [***] of resolution of the dispute in accordance with <u>Section 15.1</u> (Dispute Resolution).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z92202eec900a4064b9f67daf61501089" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.12._Right_to_Offset._Ionis_will_have_t"></a><a name="z_bookmark97"></a><font style="font-weight: bold;">9.12.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Right to Offset</font>. Ionis will have the right to offset any amount owed by Metagenomi to Ionis that are (a) [***], or (b) [***], in each case, against any payments owed by
                Ionis to Metagenomi under this Agreement. Such offsets will be in addition to any other rights or remedies available under this Agreement and Applicable Law. For clarity, the foregoing right to offset will only apply to [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z5d1f2c9d99144d7da6b78b5226bb14a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark98"></a><a name="z_TOC_250011"></a><font style="font-weight: bold;">9.13.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Records and Audits</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2008b7756f6449e2a32ad81e09dcae55" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.13.1._Books_and_Records._Each_Party_wi"></a><font style="font-weight: bold;">9.13.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Books and Records</font>. Each Party will keep (and will cause its Affiliates and Sublicensees to keep) complete and accurate books and records pertaining to (a) in the case
                of Ionis, all Internal Costs and Out-of-Pocket Costs incurred in connection with the performance of the Drug Discovery Activities, Net Sales of Ionis Products, any amounts paid under any Ionis In-License Agreement, and any costs shared by
                the Parties for the Co-Co Products pursuant to a Co-Development and Co-Commercialization Agreement (the &#8220;<font style="font-weight: bold;">Ionis Records</font>&#8221;) and&#160; (b) in the case of Metagenomi, all Internal Costs and Out-of-Pocket Costs
                incurred in connection with the performance of the Collaboration Activities, Net Sales of the Metagenomi Products, any amounts paid under any Metagenomi In-License Agreement, and any costs shared by the Parties for the Co-Co Products
                pursuant to a Co-Development and Co-Commercialization Agreement (the &#8220;<font style="font-weight: bold;">Metagenomi Records</font>&#8221;), in each case ((a) and (b)), in reasonable detail to permit the other Party to confirm the accuracy of all
                payments or costs reported for at least the preceding [***]. During the Term and for a period of [***] thereafter, each Party (the &#8220;<font style="font-weight: bold;">Auditing Party</font>&#8221;) may, upon written request and subject to this <u>Section


                  9.13</u> (Records and Audits), cause a nationally- recognized independent accounting firm (the &#8220;<font style="font-weight: bold;">Auditor</font>&#8221;), that is reasonably acceptable to the other Party (the &#8220;<font style="font-weight: bold;">Audited


                  Party</font>&#8221;) to inspect the relevant records of such Audited Party and its Affiliates to verify the payments made and amounts reported by the Audited Party and the directly related reports, statements, and books of accounts, as
                applicable.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">35</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc5b81d48dfa2451f83350501b688e214" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.13.2._Audit_Procedure._Before_beginnin"></a><font style="font-weight: bold;">9.13.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Audit Procedure</font>. Before beginning its audit, the Auditor will execute a written agreement acceptable to the Audited Party by which the Auditor agrees to keep
                confidential all information reviewed during the audit, which agreement will contain terms of non- disclosure and non-use no less stringent than those set forth in this Agreement, but otherwise will be reasonable and customary for the
                purposes of an audit of this nature. The Auditor will have the right to disclose to the Auditing Party only its conclusions regarding any payments owed under this Agreement. Each Party and its Affiliates will make their records available
                for inspection by the Auditor during regular business hours at such place or places where such records are customarily kept, upon receipt of reasonable advance notice from the Auditing Party. The records will be reviewed solely to verify
                the Audited Party&#8217;s compliance with the payment obligations and financial terms of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd8efbdf2f7e8485b8a7d47890ed878d7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z9.13.3._Frequency_Overpayments_and_Unde"></a><font style="font-weight: bold;">9.13.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Frequency; Overpayments and Underpayments</font>. Such inspection right will not be exercised more than [***] and not more frequently than [***] with respect to records
                covering any specific period of time. In addition, the Auditing Party will only be entitled to audit the books and records of the Audited Party for the [***] prior to the [***] in which the audit request is made. The Auditing Party agrees
                to hold in strict confidence all information received and all information learned in the course of any audit or inspection, except to the extent necessary to enforce its rights under this Agreement or to the extent required to comply with
                any Applicable Law or judicial order. The Auditor will provide its audit report and basis for any determination to the Audited Party at the time such report is provided to the Auditing Party before it is considered final. If the final
                result of the inspection reveals an underpayment or overpayment by either Party, then the underpaid or overpaid amount will be settled promptly plus interest due on any underpayments in accordance with <u>Section 9.15</u> (Late Fees). The
                Auditing Party will pay for such inspections, as well as its expenses associated with enforcing its rights with respect to any payments hereunder; unless such audit reveals an underpayment of amounts owed to, or an overpayment of amounts
                owed by, the Auditing Party of more than [***]% of the amount that was owed by the Audited Party or owed to the Audited Party, as applicable, with respect to the relevant period, in which case, the Audited Party will reimburse the Auditing
                Party for the reasonable expense incurred by the Auditing Party in connection with the audit.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf3c71c1cefbc4e8a9e48fd171836f368" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.14._Currency_of_Payment_Non-Refundabl"></a><a name="z_bookmark99"></a><font style="font-weight: bold;">9.14.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Currency of Payment; Non-Refundable Payments</font>. All amounts to be paid pursuant to this Agreement will be made in United States Dollars and will be paid by wire transfer
                in immediately available funds to a bank account designated by the receiving Party. The rate of exchange to be used in computing the amount of currency equivalent in U.S. Dollars owed to a Party under this Agreement will be the paying
                Party&#8217;s then-current standard exchange rate methodology employed for the translation of foreign currency sales into U.S. Dollars in accordance with its Accounting Standards and consistently applied during the period. Any provisions of this
                Agreement that describe a payment as non-refundable will be without prejudice to either Party&#8217;s right to bring a claim for breach of this Agreement, misrepresentation, or any other claim permissible under Applicable Law, including seeking
                recovery of payments made and damages for loss.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7bdba29f55a44c28b69270e4eec6ffbb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.15._Late_Fees._If_a_Party_does_not_rec"></a><a name="z_bookmark100"></a><font style="font-weight: bold;">9.15.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Late Fees</font>. If a Party does not receive payment of any undisputed sum due to it on or before the due date set forth under this Agreement, then simple interest will
                thereafter accrue on the sum due to such Party from the due date until the date of payment at a per-annum rate of [***] or the maximum rate allowable under Applicable Law, whichever is lower.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">36</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf608083f9a9b4429a3280702909e072e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.16._Currency_Restrictions._If_by_reas"></a><font style="font-weight: bold;">9.16.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Currency Restrictions</font>. If, by reason of Applicable Law in any country, it becomes impossible or illegal for a Party to transfer, or have transferred on its behalf,
                payments owed to the other Party hereunder, then such Party will promptly notify the other Party of the conditions preventing such transfer and such payments will be deposited in local currency in the relevant country to the credit of the
                other Party in a recognized banking institution designated by the other Party or, if none is designated by the other Party within a period of [***], in a recognized banking institution selected by the transferring Party, as the case may be,
                and identified in a written notice given to the other Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze018f7be060541b1b21f1b223d0ebac2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z9.17._Withholding_Taxes._Either_Party_a"></a><a name="z_bookmark101"></a><font style="font-weight: bold;">9.17.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Withholding Taxes</font>. Either Party (a &#8220;<font style="font-weight: bold;">Withholding Party</font>&#8221;) may withhold from payments due to the other Party (a &#8220;<font style="font-weight: bold;">Non-Withholding Party</font>&#8221;) amounts for payment of any withholding tax that is required by Applicable Law to be paid to any taxing authority with respect to such payments, which will be remitted in accordance
                with Applicable Law. The Withholding Party will provide to the Non-Withholding Party all relevant documents and correspondence, and will also provide to the Non-Withholding Party any other cooperation or assistance on a reasonable basis as
                may be necessary to enable the Non-Withholding Party to claim exemption from such withholding taxes and to receive a refund of such withholding tax or claim a foreign tax credit. The Withholding Party will give proper evidence from time to
                time as to the payment of any such tax. The Parties will cooperate with each other in seeking deductions under any double taxation or other similar treaty or agreement from time to time in force. Such cooperation may include the Withholding
                Party making payments from a single source in the U.S., where possible. Notwithstanding the foregoing, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark102"></a><a name="z_TOC_250010"></a>Article 10</div>
      <div style="text-align: center; font-weight: bold;"> <a name="z_bookmark103"></a>Intellectual Property</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0073ba50d8314de0999052f154c612ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250009"></a><font style="font-weight: bold;">10.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Ownership of Inventions</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zbfe888f74aee448c91cbdf7f61cfda5c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.1.1._Background_Intellectual_Property"></a><a name="z_bookmark104"></a><font style="font-weight: bold;">10.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Background Intellectual Property</font>. As between the Parties, and subject to the licenses granted under this Agreement, each Party retains all rights, title, and interests
                in and to all Intellectual Property Rights that such Party owns or Controls as of the Effective Date or that it develops or otherwise acquires after the Effective Date outside the performance of the activities under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z50952bff4d9d4221ae4fd009ddad4b00" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.1.2._By_Inventorship._For_purposes_of"></a><a name="z_bookmark105"></a><font style="font-weight: bold;">10.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">By Inventorship</font>. For purposes of determining ownership under this <u>Section 10.1.2</u> (By Inventorship), inventorship will be determined in accordance with United
                States patent laws (regardless of where the applicable activities occurred).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z69b40df2b68a490eb2d40be0d2daa035" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Metagenomi_Collaboration_Technology."></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Collaboration Technology</font>. Metagenomi will be the sole owner of any Know-How discovered, developed, invented, or created solely by Metagenomi or its
                Affiliates or Third Parties acting on its or their behalf, in each case, in the performance of activities under this Agreement (&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Know-How</font>&#8221;) and any Patent Rights that Cover
                the Metagenomi Collaboration Know-How (&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Patent Rights</font>&#8221; and together with the Metagenomi Collaboration Know-How, the &#8220;<font style="font-weight: bold;">Metagenomi Collaboration
                  Technology</font>&#8221;), and will retain all of its rights thereto, subject to any rights or licenses expressly granted by Metagenomi to Ionis under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z86742980f5db4d8697859d72ce64051e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 86.9pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="zb_Ionis_Collaboration_Technology._Ioni"></a>(b)</td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis Collaboration Technology</font>. Ionis will be the sole owner of any Know-How discovered, developed, invented, or created solely by Ionis or its Affiliates or Third
                Parties acting on its or their behalf, in each case, in the performance of activities under this Agreement (&#8220;<font style="font-weight: bold;">Ionis Collaboration Know-How</font>&#8221;) and any Patent Rights that Cover the Ionis Collaboration
                Know-How (&#8220;<font style="font-weight: bold;">Ionis Collaboration Patent Rights</font>&#8221; and together with the Ionis Collaboration Know-How, the &#8220;<font style="font-weight: bold;">Ionis Collaboration Technology</font>&#8221;), and will retain all of
                its rights thereto, subject to any rights or licenses expressly granted by Ionis to Metagenomi under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">37</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc4b2f5fdc6894795aa4c28ea08d73b63" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Joint_Collaboration_Technology._Any_"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Joint Collaboration Technology</font>. Any Know-How discovered, developed, invented, or created jointly by (i) Ionis, its Affiliates, or Third Parties acting on its or their
                behalf and (ii) Metagenomi, its Affiliates, or Third Parties acting on its or their behalf, in each case, in the performance of activities under this Agreement (including in any meeting of the JSC or any Subcommittee) (such Know-How, &#8220;<font style="font-weight: bold;">Joint Collaboration Know-How</font>&#8221;), and any Patent Rights that Cover such Joint Collaboration Know-How (&#8220;<font style="font-weight: bold;">Joint Collaboration Patent Rights</font>,&#8221; and together with the Joint
                Collaboration Know-How, the &#8220;<font style="font-weight: bold;">Joint Collaboration Technology</font>&#8221;), will be owned jointly by Ionis and Metagenomi on an equal and undivided basis, including all rights thereto, subject to any rights or
                licenses expressly granted by one Party to the other Party under this Agreement. Except as expressly provided in this Agreement, neither Party will have any obligation to account to the other for profits with respect to, or to obtain any
                consent of the other Party to license or exploit, Joint Collaboration Technology by reason of joint ownership thereof, and each Party hereby waives any right it may have under the laws of any jurisdiction to require any such consent or
                accounting.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z56418cf594c1489d9a18d8d947ffb2ab" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.1.3._Disclosure._During_the_Term_a"></a><font style="font-weight: bold;">10.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Disclosure</font>. During the Term, (a) Ionis will promptly disclose to designated Metagenomi personnel (including Metagenomi scientific and intellectual property personnel)
                in writing, and will cause its Affiliates to so disclose, the discovery, development, invention, or creation of any Ionis Collaboration Know-How or Ionis Collaboration Patent Right and (b) Metagenomi will promptly disclose to designated
                Ionis personnel (including Ionis scientific and intellectual property personnel) in writing, and will cause its Affiliates to so disclose, the discovery, development, invention, or creation of any Metagenomi Collaboration Know-How or
                Metagenomi Collaboration Patent Rights.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z56ba4e465b55475d8342d55d6f6c2dc7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark106"></a><a name="z_TOC_250008"></a><font style="font-weight: bold;">10.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Patent Prosecution</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z66e3f9d893c84acab0c3cc49481dac9d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.2.1._Ionis-Prosecuted_Patent_Rights."></a><font style="font-weight: bold;">10.2.1.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis-Prosecuted Patent Rights</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z542e83c186334312abb8e129a091c88e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_As_between_the_Parties_Ionis_will_h"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">As between the Parties, Ionis will have the first right, but not the obligation, to control the Prosecution and Maintenance of all Product-Specific Patent Rights, all Joint Collaboration Patent Rights, and
                all Ionis Collaboration Patent Rights (&#8220;<font style="font-weight: bold;">Ionis-Prosecuted Patent Rights</font>&#8221;). Ionis will be the &#8220;Prosecuting Party&#8221; with respect to all Ionis-Prosecuted Patent Rights. Ionis will be responsible for and
                pay all future costs and expenses incurred in connection with the Prosecution and Maintenance of the Ionis-Prosecuted Patent Rights. Ionis will keep Metagenomi reasonably informed as to material developments with respect to the Prosecution
                and Maintenance of the Ionis-Prosecuted Patent Rights and will provide Metagenomi a reasonable opportunity to review and comment on substantive communications from any patent authority in the Territory regarding the Ionis- Prosecuted Patent
                Rights, as well as drafts of any substantive filings or responses to be made to such patent authorities in advance of submitting such filings or responses. Ionis will consider Metagenomi&#8217;s comments regarding such communications and drafts
                in good faith but is not required to implement such comments. In addition, Ionis will provide Metagenomi with (i) copies of all final substantive filings and responses made to any patent authority with respect to the Ionis-Prosecuted Patent
                Rights in a timely manner following submission thereof and (ii) notice in advance of abandoning any such Ionis-Prosecuted Patent Rights.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">38</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf40fbbc2ea7c46f48d01d0a020e7efdf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_If_during_the_Term_Ionis_decides_t"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">If, during the Term, Ionis decides that it is no longer interested in the Prosecution and Maintenance of a particular Product-Specific Patent Right or Joint Collaboration Patent Right, then it will promptly
                provide written notice to Metagenomi of such decision; <font style="font-style: italic;">provided </font>that any such notice will be at least [***] in advance of any time based deadlines by which an action must be taken to establish or
                preserve any such Patent Right. Unless Ionis decides to no longer Prosecute and Maintain a particular Product-Specific Patent Right or Joint Collaboration Patent Right for strategic reasons, Metagenomi may, upon written notice to Ionis,
                assume the Prosecution and Maintenance of such Patent Right at Metagenomi&#8217;s sole cost and expense. In such event Metagenomi will be responsible for 100% of the costs and expenses of the Prosecution and Maintenance of such Patent Right, and
                Metagenomi will thereafter be the &#8220;Prosecuting Party&#8221; with respect thereto for all purposes under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0c038a5cfdb64c549303bdc32d8443d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.2.2._Metagenomi-Prosecuted_Patent_Rig"></a><font style="font-weight: bold;">10.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi-Prosecuted Patent Rights</font>. As between the Parties, Metagenomi will have the sole right, but not the obligation, to control the Prosecution and Maintenance of
                the Licensed Patent Rights and Metagenomi Collaboration Patent Rights, in each case, that are not Product-Specific Patent Rights (such Patent Rights, the &#8220;<font style="font-weight: bold;">Metagenomi-Prosecuted Patent Rights</font>&#8221;) in
                accordance with this Agreement. Metagenomi will be the &#8220;Prosecuting Party&#8221; with respect to all Metagenomi-Prosecuted Patent Rights. Metagenomi will be responsible for and pay all future costs and expenses incurred in connection with the
                Prosecution and Maintenance of the Metagenomi-Prosecuted Patent Rights. Metagenomi will keep Ionis reasonably informed as to material developments with respect to the Prosecution and Maintenance of the Metagenomi-Prosecuted Patent Rights
                and will provide Ionis a reasonable opportunity to review and comment on substantive communications from any patent authority in the Territory regarding the Metagenomi- Prosecuted Patent Rights, as well as drafts of any substantive filings
                or responses to be made to such patent authorities in advance of submitting such filings or responses. Metagenomi will consider Ionis&#8217; comments regarding such communications and drafts in good faith but is not required to implement such
                comments. In addition, Metagenomi will provide Ionis with (a) copies of all final substantive filings and responses made to any patent authority with respect to the Metagenomi-Prosecuted Patent Rights in a timely manner following submission
                thereof and (b) notice in advance of abandoning any such Metagenomi-Prosecuted Patent Rights.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z136407c97e614c3c8094091c67338fa7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.2.3._Cooperation._The_non-Prosecuting"></a><font style="font-weight: bold;">10.2.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Cooperation</font>. The non-Prosecuting Party will (a) obtain and deliver to the Prosecuting Party any necessary documents for the Prosecuting Party to exercise its rights to
                prepare, prosecute, defend, and maintain all Patent Rights pursuant to this <u>Section 10.2</u> (Patent Prosecution), (b) render all signatures that will be necessary in connection with all such patent filings, and (c) assist the
                Prosecuting Party in all other reasonable ways that are necessary for the issuance of those Patent Rights for which such Prosecuting Party is responsible, as well as for the Prosecution and Maintenance of such Patent Rights.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zea93613b755c4da0a3f5b71d0c91fe8d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.2.4._Coordination_in_Prosecution._Not"></a><font style="font-weight: bold;">10.2.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Coordination in Prosecution</font>. Notwithstanding Metagenomi&#8217;s right to Prosecute and Maintain the Metagenomi-Prosecuted Patent Rights, the Parties will, and will cause
                their Affiliates to, cooperate and implement reasonable patent filing and prosecution strategies (including filing divisionals, continuations or otherwise) so that, to the extent reasonably feasible, Product-Specific Patent Rights and other
                Licensed Patent Rights are pursued in mutually exclusive patent applications.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">39</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za5a6295c1bf348118d25946191d8a6b1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark107"></a><a name="z_TOC_250007"></a><font style="font-weight: bold;">10.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Patent Enforcement</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z43d04883fb0d469bae623b6f9d183563" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.3.1._Notification._Each_Party_will_us"></a><a name="z_bookmark108"></a><font style="font-weight: bold;">10.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Notification</font>. Each Party will use reasonable efforts to promptly notify the other in the event of any actual, likely, or suspected infringement of any Ionis-Prosecuted
                Patent Right or Metagenomi-Prosecuted Patent Right (an &#8220;<font style="font-weight: bold;">Infringement</font>&#8221;), including any Infringement that arises as a result of the making, using, offering to sell, selling, or importing of a product
                that would be competitive with a Licensed System or Licensed Product (a &#8220;<font style="font-weight: bold;">Competitive Infringement</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf1c8bdb315aa4ca29a67c681043488cd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.3.2._Competitive_Infringements."></a><a name="z_bookmark109"></a><font style="font-weight: bold;">10.3.2.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Competitive Infringements</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za857c67bc4024b258cb15a4b2f12b397" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Ionis_will_have_the_first_right_but"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will have the first right, but not the obligation, to institute, prosecute, and control a Proceeding to enforce the Ionis-Prosecuted Patent Rights against any Competitive Infringement at its own
                expense. If Ionis fails to initiate a Proceeding within a period of 90 days after written notice of a Competitive Infringement is first provided by a Party under <u>Section 10.3.1</u> (Notification), then Metagenomi will have the right to
                initiate and control a Proceeding to enforce the applicable Patent Right against such Competitive Infringement by counsel of its own choice; <font style="font-style: italic;">provided </font>that if Ionis notifies Metagenomi during such
                90-day period that it is electing in good faith not to institute any Proceeding to enforce Ionis-Prosecuted Patent Rights against such Competitive Infringement for strategic reasons, then Metagenomi will not have the right to initiate and
                control any Proceeding to enforce such Patent Rights against such Competitive Infringement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z67757ad1d201498aa4cf818218277074" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Metagenomi_will_have_the_first_right"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will have the first right, but not the obligation, to institute, prosecute, and control a Proceeding to enforce the Metagenomi-Prosecuted Patent Rights against any Competitive Infringement at its
                own expense. If Metagenomi fails to initiate a Proceeding within a period of 90 days after written notice of a Competitive Infringement is first provided by a Party under <u>Section 10.3.1</u> (Notification), then Ionis will have the right
                to initiate and control a Proceeding to enforce the applicable Patent Right against such Competitive Infringement by counsel of its own choice; <font style="font-style: italic;">provided </font>that if Metagenomi notifies Ionis during
                such 90-day period that it is electing in good faith not to institute any Proceeding to enforce Metagenomi-Prosecuted Patent Rights against such Competitive Infringement for strategic reasons, then Ionis will not have the right to initiate
                and control any Proceeding to enforce such Patent Rights against such Competitive Infringement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6742f9545444439da783ab15c0e17376" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.3.3._Proceedings_for_Infringements_ot"></a><font style="font-weight: bold;">10.3.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Proceedings for Infringements other than Competitive Infringements</font>. During the Term, (a) Metagenomi will have the sole right, but not the obligation, to initiate a
                Proceeding against any Infringement that is not a Competitive Infringement with respect to any Licensed Patent Rights, at Metagenomi&#8217;s sole discretion and at Metagenomi&#8217;s sole cost and expense and (b) the Parties will jointly agree upon any
                initiation of a Proceeding against any Infringement that is not a Competitive Infringement with respect to any Joint Collaboration Patent Right; <font style="font-style: italic;">provided </font>that neither Party will unreasonably
                withhold its agreement to initiate any such Proceeding with respect to any Joint Collaboration Patent Right (as applicable) upon the reasonable request of the other Party.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">40</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zafa6046d9f464664b37a94fcda23df3b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.3.4._Collaboration._Each_Party_will_p"></a><font style="font-weight: bold;">10.3.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Collaboration</font>. Each Party will provide to the enforcing Party reasonable assistance in any Proceeding brought under this <u>Section 10.3</u> (Patent Enforcement), at
                such enforcing Party&#8217;s request and expense, including to be named in such action if required by Applicable Law to pursue such action. The enforcing Party will keep the other Party regularly informed of the status and progress of such
                enforcement efforts, will reasonably consider the other Party&#8217;s comments on any such efforts, including determination of litigation strategy and filing of material papers to the competent court. The non-enforcing Party will be entitled to
                separate representation in such matter by counsel of its own choice and at its own expense, but such Party will at all times cooperate fully with the enforcing Party. The enforcing Party will not settle any Proceeding that it brought under
                <u>Section 10.3.2</u> (Competitive Infringements) in any manner that would limit the rights of the other Party or impose any obligation on the other Party, without the prior written consent of the other Party, which consent will not be
                unreasonably withheld, conditioned, or delayed.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcaa1bd2048b34632b1104e1c14b49a1a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.3.5._Expenses_and_Recoveries._Any_amo"></a><font style="font-weight: bold;">10.3.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Expenses and Recoveries</font>. Any amount recovered in any Proceeding under this <u>Section</u><u> 10.3</u> (Patent Enforcement), including any amount recovered in any
                settlement of such Proceeding, will first be used to [***] and will thereafter be for (a) with respect to any Competitive Infringement, the benefit of [***]; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that to the extent any such amount is [***], then such amount will, [***], and (b) with respect to any Infringement that is not a Competitive Infringement, for the benefit of [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4ba9bf05680d4a07b8125f73bd6d4fd3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.4._Defense_of_Claims_Brought_by_Third"></a><a name="z_bookmark110"></a><font style="font-weight: bold;">10.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Defense of Claims Brought by Third Parties</font>. If any Third Party brings a claim or otherwise asserts that a Licensed Product or Licensed System infringes such Third
                Party&#8217;s Patent Rights or misappropriates such Third Party&#8217;s Know-How (each, a &#8220;<font style="font-weight: bold;">Third Party Infringement Claim</font>&#8221;), then the Party first having notice of the claim or assertion will promptly notify the
                other Party in writing. Subject to [***], [***] will have the sole right, but not the obligation, to undertake and control the defense or settlement of any Third Party Infringement Claim using counsel of its choice, at its cost and expense.
                If [***] is named as a defendant in such suit, [***] will have the right to participate in such defense and settlement with its own counsel, at its cost. [***] will not enter into any settlement of any Third Party Infringement Claim that is
                instituted or threatened to be instituted against [***] without [***] prior written consent, which will not be unreasonably withheld, conditioned, or delayed; except that such consent will not be required if such settlement includes a
                release of all liability in favor of [***] or an assumption of any unreleased liability by [***]. As requested by [***], [***] will provide reasonable cooperation and assistance to [***] in connection with [***] control of the defense or
                settlement of a Third Party Infringement Claim. Such cooperation and assistance will include executing all necessary and proper documents and taking such actions as will be appropriate to allow [***] to control the defense and settlement of
                such Third Party Infringement Claim. [***] will [***]; except that [***] will have no obligation to [***]. [***] will keep [***] reasonably informed of the progress of any Third Party Infringement Claim. To the extent reasonable, both
                Parties will cooperate in good faith to (a) ensure that [***] and (b) [***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z3378f803e1d94e23a592861472d1ab8c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.5._Patent_Listing._Ionis_will_have_th"></a><font style="font-weight: bold;">10.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Patent Listing</font>. Ionis will have the sole right, but not the obligation, to determine which Ionis- Prosecuted Patent Rights will be listed in connection with the
                Regulatory Approval for a Licensed Product pursuant to 21 U.S.C. &#167; 355(b)(1)(G), any similar statutory or regulatory requirement enacted in the future regarding biologic products, or any similar statutory or regulatory requirement in any
                non-U.S. country or other regulatory jurisdiction. The Parties will discuss and mutually agree on which Metagenomi-Prosecuted Patent Rights will be listed in connection with the Regulatory Approval for a Licensed Product pursuant to 21
                U.S.C. &#167; 355(b)(1)(G), any similar statutory or regulatory requirement enacted in the future regarding biologic products, or any similar statutory or regulatory requirement in any non-U.S. country or other regulatory jurisdiction.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">41</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zb6adedd17cc44fd4bfb87fe9281bdbf3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.6._Common_Ownership_Legislation._Notw"></a><a name="z_bookmark111"></a><font style="font-weight: bold;">10.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Common Ownership Legislation</font>. Notwithstanding anything to the contrary in this <u>Article 10</u> (Intellectual Property), neither Party will have the right to make an
                election under the Common Ownership Legislation when exercising its rights under this <u>Article 10</u> (Intellectual Property) without the prior written consent of the other Party, which will not be unreasonably withheld, conditioned, or
                delayed. With respect to any such permitted election, the Parties will use reasonable efforts to cooperate and coordinate their activities with respect to any submissions, filings, or other activities in support thereof. The Parties
                acknowledge and agree that this Agreement is a &#8220;joint research agreement&#8221; as defined in the Common Ownership Legislation. Notwithstanding the foregoing, the other Party&#8217;s consent under this <u>Section 10.6</u> (Common Ownership
                Legislation) will not be required in connection with an obviousness-type double patenting rejection in any patent application claiming a Licensed System, Licensed Product, or uses thereof.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z0fc9f5ce0da84b39bdca7de354435e69" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250006"></a><font style="font-weight: bold;">10.7.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Patent Term Extension</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc3088721c1b1420dbf334835aed7e92a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.7.1._Ionis-Prosecuted_Patent_Rights._"></a><font style="font-weight: bold;">10.7.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis-Prosecuted Patent Rights</font>. Ionis will be solely responsible for obtaining patent term restoration for the Ionis-Prosecuted Patent Rights in any country in the
                Territory under any statute or regulation equivalent or similar to 35 U.S.C. &#167; 156, where applicable to a Licensed Product. Ionis will determine which relevant Ionis-Prosecuted Patent Rights will be extended (including by filing
                supplementary protection certificates and any other extensions that are now or in the future become available). Metagenomi will abide by Ionis&#8217; determination and cooperate, as reasonably requested by Ionis, in connection with the foregoing
                (including by providing appropriate information and executing appropriate documents).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb8a819fbffc2418eae121e2f7be8676d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z10.7.2._Metagenomi-Prosecuted_Patent_Rig"></a><font style="font-weight: bold;">10.7.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi-Prosecuted Patent Rights</font>. The Parties will mutually agree on the strategy for obtaining patent term restoration for the Metagenomi-Prosecuted Patent Rights
                in any country in the Territory under any statute or regulation equivalent or similar to 35 U.S.C. &#167; 156, where applicable to a Licensed Product. The Parties will mutually agree on which relevant Metagenomi-Prosecuted Patent Rights will be
                extended (including by filing supplementary protection certificates and any other extensions that are now or in the future become available) and will cooperate with each other in connection with the foregoing (including by providing
                appropriate information and executing appropriate documents).</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify; margin-right: 5.65pt; margin-left: 87pt;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z90d409f6319b4ba08e67d25f7ce13bf6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.8._Recording._If_Ionis_deems_it_neces"></a><a name="z_bookmark112"></a><font style="font-weight: bold;">10.8.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Recording</font>. If Ionis deems it necessary or desirable to register or record this Agreement or evidence of this Agreement with any patent office or other appropriate
                Governmental Authority in one or more jurisdictions in the Territory, then Metagenomi will reasonably cooperate to execute and deliver to Ionis any documents accurately reflecting or evidencing this Agreement that are necessary or
                desirable, in Ionis&#8217; reasonable judgment, to complete such registration or recordation. Ionis will [***] in complying with the provisions of this <u>Section 10.8</u> (Recording).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc34878ae94204af4889f4f539e147e5a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.9._Unitary_Patent_System._Ionis_will_"></a><font style="font-weight: bold;">10.9.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Unitary Patent System</font>. Ionis will have the exclusive right to opt-in or opt-out of the EU Unitary Patent System for all Licensed Patent Rights and Joint Collaboration
                Patent Rights. For clarity, &#8220;to opt-in or opt-out&#8221; refers to both the right to have a European patent application or an issued European patent registered to have unitary effect within the meaning of Regulation (EU) No 1257/2012 of December
                17, 2012 as well as the Agreement on a Unified Patent Court as of February 19, 2013; and to the right to opt-in or opt-out from the exclusive competence of the Unified Patent Court in accordance with Article 83(3) of that Agreement on a
                Unified Patent Court. Without limiting the generality of the foregoing, unless a Party or its Affiliate has expressly opted-in to the EU Unitary Patent System with respect to a given Patent Right, the other Party will not initiate any
                action under the EU Unitary Patent System without such Party&#8217;s prior written approval, such approval to be granted or withheld in such Party&#8217;s sole discretion.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze94511edd01c444a8d3d11b7f79bf286" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.10._Trademarks._As_between_the_Partie"></a><font style="font-weight: bold;">10.10.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Trademarks</font>. As between the Parties, all trademarks and trade dress rights used in connection with the Commercialization of the Licensed Products in the Field in the
                Territory will be owned exclusively by Ionis.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">42</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z9cd997f2240649108cea0f8ea36e8bd3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z10.11._Common_Interest._All_information_"></a><font style="font-weight: bold;">10.11.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Common Interest</font>. All information exchanged between the Parties regarding the Prosecution and Maintenance, and enforcement and defense, of the Patent Rights under this <u>Article


                  10</u> (Intellectual Property) will be deemed Confidential Information of the disclosing Party. In addition, the Parties acknowledge and agree that, with regard to such Prosecution and Maintenance, and enforcement and defense of the
                Patent Rights under this <u>Article 10</u> (Intellectual Property), the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in
                nature. The Parties agree and acknowledge that they have not waived, and nothing in this Agreement constitutes a waiver of, any legal privilege concerning the Patent Rights under this <u>Article 10</u> (Intellectual Property), including
                privilege under the common interest doctrine and similar or related doctrines. Notwithstanding anything to the contrary contained herein, to the extent a Party has a good faith belief that any information required to be disclosed by such
                Party to the other Party under this <u>Article 10</u> (Intellectual Property) is protected by attorney-client privilege or any other applicable legal privilege or immunity, such Party will not be required to disclose such information and
                the Parties will in good faith cooperate to agree upon a procedure (including entering into a specific common interest agreement, disclosing such information on a &#8220;for counsel eyes only&#8221; basis or similar procedure) under which such
                information may be disclosed without waiving or breaching such privilege or immunity.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark113"></a><a name="z_bookmark114"></a><a name="z_TOC_250005"></a>Article 11</div>
      <div style="text-align: center; font-weight: bold;"> Confidentiality</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z00a5ad10c8bb4449b6414d595985b541" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark115"></a><a name="z_TOC_250004"></a><font style="font-weight: bold;">11.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Confidential Information</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd76beb416bfd46f2becc6a2d4d63ff1a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.1.1._General._Each_Party_will_maintai"></a><a name="z_bookmark116"></a><font style="font-weight: bold;">11.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">General</font>. Each Party will maintain all Confidential Information disclosed to it or its representatives (the &#8220;<font style="font-weight: bold;">Receiving Party</font>&#8221;) by
                or on behalf the other Party (the &#8220;<font style="font-weight: bold;">Disclosing Party</font>&#8221;) in strict confidence during the Term of this Agreement and for a period of [***] after the expiration or termination of this Agreement; <font style="font-style: italic;">provided </font>that any Confidential Information of either Party that constitutes a trade secret will continue to be subject to the terms of this <u>Article 11</u> (Confidentiality) in perpetuity, so long as
                such information remains a trade secret. Each Party will use all such disclosed Confidential Information only to the extent necessary for purposes of this Agreement, including exercising the licenses and rights hereunder, and will not
                disclose such Confidential Information to any Third Party without the prior written consent of the Disclosing Party, except as permitted under this Agreement. Each Party will notify the other Party promptly on discovery of any unauthorized
                use or disclosure by a Party of the other Party&#8217;s Confidential Information, including the other Party&#8217;s trade secrets.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1aeeea233b4b482fb731b542e5b80d47" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.1.2._Confidential_Information_of_Each"></a><font style="font-weight: bold;">11.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Confidential Information of Each Party</font>. All information disclosed prior to the Effective Date pursuant to the Confidentiality Agreement between the Parties dated [***]
                (the &#8220;<font style="font-weight: bold;">Confidentiality Agreement</font>&#8221;), by Metagenomi to Ionis will be Confidential Information of Metagenomi and by Ionis to Metagenomi will be Confidential Information of Ionis. All Ionis Royalty Reports
                and reports identifying Ionis Product Development Milestone Events, Ionis Product Regulatory Milestone Events, and Ionis Product Sales Milestone Events will be considered Confidential Information of Ionis. All Metagenomi Royalty Reports and
                reports identifying Metagenomi Product Milestone Events will be the Confidential Information of Metagenomi. The Product-Specific Know-How, Joint Collaboration Know-How, and the non-disclosed terms of this Agreement will be the Confidential
                Information of each Party.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">43</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za515f396b03a4d0bb7f5dd785b7f37b0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.1.3._Exceptions_to_Confidentiality._T"></a><font style="font-weight: bold;">11.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Exceptions to Confidentiality</font>. The following information will not be Confidential Information of the Disclosing Party, and accordingly the obligations of each Receiving
                Party imposed by <u>Section 11.1.1</u> (General) will not apply to any such information that: (a) was known to the Receiving Party without an obligation to keep such information confidential prior to the Effective Date other than as a
                result of disclosure under any other agreement between the Parties, including the Confidentiality Agreement (as demonstrated by documentary evidence); (b) is or becomes generally available to the public through means other than an
                unauthorized disclosure by the Receiving Party, its Affiliates, or any agents to whom it or they disclosed such information; (c) was or subsequently is disclosed to the Receiving Party without restriction by a Third Party having a <font style="font-style: italic;">bona fide </font>right to disclose such Confidential Information without breaching any obligation to the Disclosing Party; or (d) is developed independently by the Receiving Party without benefit of or
                recourse to any of the Disclosing Party&#8217;s Confidential Information (as demonstrated by documentary evidence). For clarity, (i) specific aspects or details of Confidential Information will not be deemed to be within the public domain or in
                the possession of the Receiving Party merely because the Confidential Information is embraced by more general information in the public domain or in the possession of the Receiving Party; and (ii) any combination of Confidential Information
                will not be considered in the public domain or in the possession of the Receiving Party merely because individual elements of such Confidential Information are in the public domain or in the possession of the Receiving Party unless the
                combination and its principles are in the public domain or in the possession of the Receiving Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z96f3a10b5dbb4eb0b3dc07d984588b1b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.1.4._Permitted_Disclosures._The_Recei"></a><a name="z_bookmark117"></a><font style="font-weight: bold;">11.1.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Permitted Disclosures</font>. The Receiving Party may disclose Confidential Information of the Disclosing Party to the extent (and solely to the extent) that such disclosure
                is reasonably necessary in the following instances:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc67dc4f962e4408e8305e72562225739" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_i_the_prosecution_and_maintenance_"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">(i) the prosecution and maintenance of Licensed Patent Rights and Joint Collaboration Patent Rights, in each case, in accordance with the terms of this Agreement; or (ii) Regulatory Submissions and other
                filings with Governmental Authorities (including Regulatory Authorities), as necessary for the Exploitation of a Licensed Product;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7599d74c07934b3e916b48174acc6199" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_disclosure_of_the_existence_and_appl"></a><a name="z_bookmark118"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">disclosure of the existence and applicable terms of this Agreement and the status and results of Exploitation of one or more Licensed Products to actual or <font style="font-style: italic;">bona fide </font>potential


                investors, acquirors, Sublicensees, lenders, and other financial or commercial partners (including in connection with any royalty factoring transaction), and their respective attorneys, accountants, banks, investors, and advisors, solely
                for the purpose of evaluating or carrying out an actual or potential investment, acquisition, sublicense, debt transaction, or collaboration; <font style="font-style: italic;">provided </font>that, in each such case, (i) such Persons are
                bound by obligations of confidentiality, non-disclosure, and non-use provisions at least as restrictive or protective of the Parties as those set forth in this Agreement or otherwise customary for such type and scope of disclosure, and (ii)
                that any such disclosure is limited to the maximum extent practicable for the particular context in which it is being disclosed; <font style="font-style: italic;">provided </font>that in no event will a disclosure of Confidential
                Information under this <u>Section&#160;11.1.4(b)</u> be made, with respect to Ionis as the Receiving Party, to [***] or with respect to Metagenomi as the Receiving Party, to [***], in each case, without the prior written consent of the other
                Party;</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">44</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z7551292e1e5e45668e61ed02b466a61b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_to_comply_with_Applicable_Law_wheth"></a><a name="z_bookmark119"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">to comply with Applicable Law (whether generally or in pursuit of an application for listing of securities) including the United States Securities and Exchange Commission or equivalent foreign agency or
                regulatory body, or otherwise required by judicial or administrative process; <font style="font-style: italic;">provided </font>that in each such event, as promptly as reasonably practicable and to the extent not prohibited by Applicable
                Law or judicial or administrative process, such Party will notify the other Party of such required disclosure and provide a draft of the disclosure to the other Party reasonably in advance of such filing or disclosure for the other Party&#8217;s
                review and comment. The non-disclosing Party will provide any comments as soon as practicable, and the disclosing Party will consider in good faith any timely comments provided by the non-disclosing Party; <font style="font-style: italic;">provided


                </font>that the disclosing Party may or may not accept such comments in its sole discretion. Confidential Information that is disclosed in order to comply with Applicable Law or by judicial or administrative process pursuant to this <u>Section



                  11.1.4(c)</u>, in each case, will remain otherwise subject to the confidentiality and non-use provisions of this <u>Article 11</u> (Confidentiality) with respect to the Party disclosing such Confidential Information, and such Party will
                take all steps reasonably necessary, including seeking of confidential treatment or a protective order for a period of at least [***] (to the extent permitted by Applicable Law or Governmental Authority), to ensure the continued
                confidential treatment of such Confidential Information, and each Party will be responsible for its own legal and other external costs in connection with any such filing or disclosure pursuant to this <u>Section 11.1.4(c)</u>;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd621aafd020b42e2b385e66959027fa9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zd_to_prosecute_or_defend_litigation_so"></a>(d)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">to prosecute or defend litigation so long as there is [***] prior written notice given by the Receiving Party before filing, and to enforce Patent Rights in connection with the Receiving Party&#8217;s rights and
                obligations pursuant to this Agreement; and</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1d577f159e654a359669d747ad59318c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="ze_to_allow_the_Receiving_Party_to_exer"></a>(e)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">to allow the Receiving Party to exercise its rights and perform its obligations hereunder; <font style="font-style: italic;">provided </font>that such disclosure is covered by terms of confidentiality and
                non-use at least as restrictive as those set forth herein.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="margin: 0px 0px 0px 123pt; text-align: justify;"><a name="If_and_whenever_any_Confidential_Informa"></a>If and whenever any Confidential Information is disclosed in accordance with this <u>Section 11.1.4</u> (Permitted Disclosures), such
        disclosure will not cause any such information to cease to be Confidential Information except to the extent that such disclosure results in a public disclosure of such information (other than by breach of this Agreement).</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za757bac6f6a5438290eb7212ea65d070" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z11.2._No_Use_of_Name._Neither_Party_will"></a><font style="font-weight: bold;">11.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">No Use of Name</font>. Neither Party will use the other Party&#8217;s name, logo, or Trademarks in any promotional materials or advertising without the prior written consent of the
                other Party, except as provided under this Agreement or required by Applicable Law, in which case the Party disclosing such name, logo, or Trademarks will give advance notice of such use and otherwise comply with <u>Section 11.1.4(c)</u>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z84f15ce32e9145d188f3d84e46083205" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z11.3._Residual_Knowledge._Notwithstandin"></a><a name="z_bookmark120"></a><font style="font-weight: bold;">11.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Residual Knowledge</font>. Notwithstanding any provision to the contrary set forth in this Agreement, a Receiving Party will not be liable for the use of any knowledge,
                technique, experience, or Know- How that is retained in the unaided memory of any officers, directors, agents, contractors, or employees of such Receiving Party after having access to such Confidential Information (&#8220;<font style="font-weight: bold;">Residual Knowledge</font>&#8221;), <font style="font-style: italic;">provided </font>that such officer, director, agent, contractor, or employee (a) has not intentionally memorized such Residual Knowledge, (b) is
                not aware at the time of use that such Residual Knowledge is the Confidential Information of the Disclosing Party, and (c) has not been directed or encouraged by the Receiving Party to memorize such Residual Knowledge. Any use made by the
                Receiving Party of any such Residual Knowledge is on an &#8220;as is, where is&#8221; basis, with all faults and all representations and warranties disclaimed and at its sole risk. For clarity, no license under any Patent Right is granted pursuant to
                this <u>Section 11.3</u> (Residual Knowledge).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">45</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z42e51c3e7c074dcbbf79ffa94a198fad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z11.4._Public_Announcements_and_Subsequen"></a><a name="z_bookmark121"></a><font style="font-weight: bold;">11.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Public Announcements and Subsequent Disclosures</font>. Except as may be expressly permitted under <u>Section 11.1.4</u> (Permitted Disclosures), neither Party will make any
                public announcement regarding this Agreement without the prior written approval of the other Party, except for either Party&#8217;s references to the other as the licensor or licensee (as applicable) or a collaboration partner under this
                Agreement. For clarity, Ionis may make scientific publications or public announcements concerning Ionis&#8217; Exploitation of any Licensed Product under this Agreement pursuant to <u>Section 11.5.1</u> (Ionis Publications); <font style="font-style: italic;">provided </font>that, except as permitted under <u>Section 11.1.4</u> (Permitted Disclosures), Ionis will not disclose any of Metagenomi&#8217;s Confidential Information in any such publication or announcement
                without obtaining Metagenomi&#8217;s prior written consent to do so. The Parties may each issue, or, by agreement of the Parties, may jointly issue, a press release announcing the signing of this Agreement after the Effective Date. The press
                release(s) to be issued by the Parties on or after the Effective Date will be substantially in the form of the press release(s) attached hereto as <u>Schedule 11.4</u> (Press Release(s)). After the issuance of any such press release or any
                other permitted public disclosure by a Party, each Party may make subsequent public disclosures reiterating such information without having to obtain the other Party&#8217;s prior consent and approval so long as the information in such press
                release or other public announcement remains true, correct, and the most current information with respect to the subject matters set forth therein.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="ze782216b7083452eb7871c2dee78edae" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250003"></a><font style="font-weight: bold;">11.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Publications</font>.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z39ebf59a13f44fe58f2f6c4fd7965786" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.5.1._Ionis_Publications."></a><a name="z_bookmark122"></a><font style="font-weight: bold;">11.5.1.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Ionis Publications</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za3bb5358fe9642d8a697fe89e20b9a78" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_During_the_Collaboration_Term_Ionis"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">During the Collaboration Term, Ionis will submit to Metagenomi for review any proposed academic, scientific, or medical publication or public presentation related to any Licensed System or Licensed Product or
                to any activities conducted pursuant to this Agreement. Metagenomi will review such publication or presentation for purposes of determining whether any portion of the proposed publication or presentation contains Metagenomi&#8217;s Confidential
                Information. Ionis will submit written copies of such proposed publication or presentation to Metagenomi no later than [***] before submission for publication or presentation (or [***] in advance in the case of an abstract). Metagenomi will
                provide its comments with respect to such publications and presentations within [***] after its receipt of such written copy (or [***] in the case of an abstract). Metagenomi will have the right: (i) to require the removal of its
                Confidential Information from any such publication or presentation and (ii) to request a reasonable delay in publication or presentation in order to protect patentable information. If Metagenomi requests such a delay, then Ionis will delay
                submission or presentation for a period of [***] after its provision of the copy of the proposed publication or disclosure to enable patent applications protecting Metagenomi&#8217;s rights in such information. Ionis will comply with standard
                academic practice regarding authorship of scientific publications and recognition of contribution of other parties in any publication.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za236fb24d48144269c3c4d9494d10c58" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Unless_otherwise_agreed_in_a_Co-Deve"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Unless otherwise agreed in a Co-Development and Co-Commercialization Agreement, after the Collaboration Term, Ionis will have the right upon at least [***] prior written notice to Metagenomi, without any
                required consent or review from Metagenomi but subject to this <u>Article 11</u> (Confidentiality), to publish or publicly disclose the scientific results of any activities conducted with respect to any Licensed System or Licensed Product
                or any other activities conducted pursuant to this Agreement; <font style="font-style: italic;">provided </font>that if Metagenomi reasonably believes that such disclosure would adversely affect the use of any Licensed System for
                applications outside of the Field, then Ionis will reasonably consider any comments to such disclosure provided by Metagenomi in such [***] period.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">46</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zb06cf9fd4f844d99842855abe13fd0d5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z11.5.2._Metagenomi_Publications._During_"></a><font style="font-weight: bold;">11.5.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi Publications</font>. During the Term, Metagenomi will not publish or publicly disclose the scientific results of any activities it conducts that are specific to the
                Licensed System or Licensed Product in the Field, or any other activities conducted pursuant to this Agreement and exclusively licensed to Ionis, in each case, without the prior written consent of Ionis (such consent not to be unreasonably
                withheld, conditioned, or delayed).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; margin-right: 114.1pt; margin-left: 123.2pt; font-weight: bold;"><a name="Article_12__Representations_Warranties"></a>Article 12</div>
      <div style="text-align: center; margin-right: 114.25pt; margin-left: 123.2pt; font-weight: bold;">Representations, Warranties, and Covenants</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z508e7fa8f6104519a59a46e174e3cd2b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.1._Mutual_Representations_and_Warrant"></a><font style="font-weight: bold;">12.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Mutual Representations and Warranties</font>. As of the Effective Date, Metagenomi and Ionis each hereby represents and warrants to the other as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.1.1._It_is_a_corporation_duly_organiz"></a><font style="font-weight: bold;">12.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">It is a corporation duly organized, validly existing, and in good standing under the laws of the jurisdiction of its organization, and has all requisite power and authority, corporate or otherwise, to
                execute, deliver, and perform this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z82a015cd0254414f87b86ebe43ea0c96" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.1.2._The_execution_and_delivery_of_th"></a><font style="font-weight: bold;">12.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The execution and delivery of this Agreement and the performance by it of the transactions contemplated hereby have been duly authorized by all necessary corporate action and will not violate (a) such Party&#8217;s
                certificate of incorporation or bylaws (or equivalent charter or organizational documents), (b) any agreement, instrument or contractual obligation to which such Party is bound, (c) any requirement of any Applicable Law, or (d) any order,
                writ, judgment, injunction, decree, determination, or award of any court or Governmental Authority presently in effect applicable to such Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z06c744e25c324aa69106ea39710790a3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.1.3._It_is_not_under_any_obligation_"></a><font style="font-weight: bold;">12.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">It is not under any obligation, contractual or otherwise, to any Person that conflicts with or is inconsistent in any respect with the terms of this Agreement or that will impede the diligent and complete
                fulfillment of its obligations hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zbd6b8d1ad1564ea3b75e519ebc15cb00" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.1.4._There_is_no_action_or_proceeding"></a><font style="font-weight: bold;">12.1.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">There is no action or proceeding pending or, to the knowledge of such Party, threatened that could reasonably be expected to impair or delay the ability of such Party to perform its obligations under this
                Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z79a8eb4c89f44774a338d75d6e416174" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.1.5._All_consents_approvals_and_aut"></a><font style="font-weight: bold;">12.1.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">All consents, approvals, and authorizations from all Governmental Authorities or other Third Parties required to be obtained by such Party in connection with this Agreement, including the grant of any
                licenses, have been obtained.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze7efa8578c23498e8418946c0ae90ea6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.2._Additional_Representations_of_Meta"></a><a name="z_bookmark123"></a><font style="font-weight: bold;">12.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Representations of Metagenomi</font>. As of the Effective Date and the date on which each new target becomes a Collaboration Target pursuant to <u>Section 2.1.1(b)</u>
                (Second Wave 1 Target) or <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available) (unless otherwise noted below), Metagenomi further represents and warrants to Ionis, that, except as set forth on <u>Schedule 12.2</u>
                (Metagenomi Disclosure Schedule) (which schedule may be updated each time a target becomes a Collaboration Target):</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1ea24971b4c6428c96fc9f0c6ddd1fed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.1._To_Metagenomis_Knowledge_the_p"></a><font style="font-weight: bold;">12.2.1.</font></td>
            <td style="vertical-align: top;">
              <div>[***] Warranty Technology [***] Metagenomi Platform [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.2._Metagenomi_Controls_all_Patent_R"></a><a name="z_bookmark124"></a><font style="font-weight: bold;">12.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi Controls all Patent Rights and Know-How owned or in-licensed by Metagenomi that are necessary to Exploit licensed systems discovered using the Metagenomi Platform in the Field. For purposes of this
                <u>Section 12.2.2</u>, &#8220;licensed systems&#8221; mean a Gene Editing protein and a Guide RNA that is designed to modulate a target.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">47</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc31b59fe073b45ebb797db0c1c17cf88" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.3._Metagenomi_is_the_sole_and_exclu"></a><font style="font-weight: bold;">12.2.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi is the sole and exclusive owner or, if applicable, exclusive licensee, of all Warranty Technology, all of which is free and clear of any liens, charges, restrictions, and encumbrances (other than
                licenses granted to Third Parties that are not inconsistent with the options, rights, and licenses granted to Ionis hereunder), and neither any assignment, license, sublicense, or other grant of any interest in or options to the Warranty
                Technology granted by Metagenomi or its Affiliates to any Third Party, nor any assignment, license, sublicense, or other grant of any interest in or options to the Warranty Technology granted by any Third Party to Metagenomi or its
                Affiliates conflicts with the options, rights, and licenses granted to Ionis hereunder, and Metagenomi is entitled to grant all rights and licenses under the Warranty Technology that it purports to grant to Ionis under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2359497b4ca04a589b113af95d636541" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.4._Schedule_1.146_Licensed_Patent_"></a><font style="font-weight: bold;">12.2.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><u>Schedule 1.146</u> (Licensed Patent Rights) sets forth a true, correct, and complete list of all Licensed Patent Rights as of the Effective Date. To the extent a Licensed Patent Right is omitted from <u>Schedule


                  1.146</u> (Licensed Patent Rights) as of the Effective Date, Metagenomi agrees and covenants to add such omitted Licensed Patent Right to <u>Schedule</u><u> 1.146</u> (Licensed Patent Rights), and that any such added Licensed Patent
                Right is deemed included in the licenses granted to Ionis pursuant to <u>Section 3.1</u> (License Grants to Ionis) as of the Effective Date; <font style="font-style: italic;">provided </font>that, for clarity, any Patent Right that
                otherwise meets the definition of Licensed Patent Rights will be deemed a Licensed Patent Right and included in the licenses granted to Ionis pursuant to <u>Section 3.1</u> (License Grants to Ionis) from the time such Patent Right existed
                whether or not it is included on <u>Schedule 1.146</u> (Licensed Patent Rights).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9b79405740b24743b7fc1e5361aa932b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.5._All_issued_Patent_Rights_within_"></a><font style="font-weight: bold;">12.2.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">All issued Patent Rights within the Warranty Technology are in full force and effect and, to Metagenomi&#8217;s Knowledge, have been Prosecuted and Maintained from the respective patent offices in accordance with
                Applicable Law. [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7e1054a8a5a947ebb61330b8dcd67e27" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.6._With_respect_to_the_Patent_Right"></a><font style="font-weight: bold;">12.2.6.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">With respect to the Patent Rights within the Warranty Technology, [***], Metagenomi has obtained assignments from any and all inventors of all inventorship rights relating to such Patent Rights, all such
                assignments of inventorship rights relating to such Patent Rights have been properly executed and recorded in the relevant U.S. and [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb0d8426b3e6f48fb8cc77311a21a796b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.7._To_Metagenomis_Knowledge_no_ci"></a><font style="font-weight: bold;">12.2.7.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">To Metagenomi&#8217;s Knowledge, no circumstances or grounds exist that would invalidate, [***], the enforceability, validity or scope of any Patent Rights within the Warranty Technology.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf20e291159c94b6f9310bd0973f8c1f3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.8._Other_than_the_Metagenomi_In-Lic"></a><font style="font-weight: bold;">12.2.8.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">[***], and no Third Party has any rights, title, or interests in or to, or any license under, any of the Licensed Technology.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6ab774de22fb4e0ebcabd57149e46f38" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.9._All_Metagenomi_In-License_Agreem"></a><font style="font-weight: bold;">12.2.9.</font></td>
            <td style="vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0435ca60729f4403b490b1782cd0447a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.10._Metagenomi_and_its_Affiliates_h"></a><font style="font-weight: bold;">12.2.10.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi and its Affiliates have taken commercially reasonable measures consistent with industry practices to protect the secrecy, confidentiality, and value of all Warranty Technology that constitutes
                trade secrets under Applicable Law [***] and, to Metagenomi&#8217;s Knowledge, such Warranty Technology has not been used, disclosed to, or discovered by any Third Party except pursuant to such confidentiality agreements and to Metagenomi&#8217;s
                Knowledge, [***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf0f3ff9faa84428b8b4852b02f5908de" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.11._The_Warranty_Technology_have_no"></a><font style="font-weight: bold;">12.2.11.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The Warranty Technology have not been created pursuant to, and are not subject to, any funding agreement with any Governmental Authority or any Third Party, and are not subject to the requirements of the
                Bayh-Dole Act or any similar provision of any Applicable Law.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">48</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zddbde9f5840e4012ba24659cdf0959e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.12._To_Metagenomis_Knowledge_no_T"></a><font style="font-weight: bold;">12.2.12.</font></td>
            <td style="vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcfc9c67cb04240e580ea4f5bdcd1176d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.13._There_are_no_judgments_or_settl"></a><font style="font-weight: bold;">12.2.13.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">There are no judgments or settlements against Metagenomi or any of its Affiliates, any pending or, to Metagenomi&#8217;s Knowledge, threatened claims or litigation in writing, or written offers for Metagenomi to
                acquire or license any Third Party Intellectual Property Rights, in each case, in connection with the Warranty Technology or the practice thereof, or relating to the transactions contemplated by this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1a4544785f60417e83f2d8a06c56cf59" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.2.14._Metagenomi_has_not_employed_an"></a><font style="font-weight: bold;">12.2.14.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi has not employed (and has not used a Subcontractor that has employed) any Person debarred by the FDA (or subject to a similar sanction of EMA or foreign equivalent), or any Person that is the
                subject of an FDA debarment investigation or proceeding (or similar proceeding of EMA or foreign equivalent), in any capacity in connection with this Agreement, the Warranty Technology, or the Metagenomi Platform.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z150627adda67448db44a3653421617c5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.3._Covenants_of_Metagenomi._Metagenom"></a><font style="font-weight: bold;">12.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Covenants of Metagenomi</font>. Metagenomi covenants to Ionis as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z738ea4a55cea4b3da8c037ebcad87fd1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.1._Metagenomi_and_its_Affiliates_wi"></a><font style="font-weight: bold;">12.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi and its Affiliates will maintain Control of all Licensed Technology and Licensed Systems owned by Metagenomi or its Affiliates at any time during the Term.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zc0465f0b2f0b4ae0846ce868ed208bff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.2._Metagenomi_and_its_Affiliates_wi"></a><font style="font-weight: bold;">12.3.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi and its Affiliates will not [***] with respect to any Licensed Technology which would adversely affect the rights granted to Ionis hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zac7e664f39114233be0af28810894b95" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.3._Neither_Metagenomi_nor_any_of_it"></a><font style="font-weight: bold;">12.3.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Neither Metagenomi nor any of its Affiliates will [***], in each case, in a manner that conflicts with or otherwise adversely affects the options, rights, and licenses granted to Ionis hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zbdac07fbcbd04c1eb91c24ddd84fb133" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.4._Metagenomi_will_maintain_and_not"></a><font style="font-weight: bold;">12.3.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will maintain and not breach, and will cause its Affiliates to maintain and not breach, the Metagenomi In-License Agreements, if any, or any license agreements that come into effect after the
                Effective Date pursuant to which Ionis receives a sublicense hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zeb67960abf314c5b9cb559956710ce8b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.5._Metagenomi_will_promptly_notify_"></a><font style="font-weight: bold;">12.3.5.</font></td>
            <td style="vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z01bf85b3325a4360ac67a1617544b122" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
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            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.6._Metagenomi_will_not_and_will_ca"></a><font style="font-weight: bold;">12.3.6.</font></td>
            <td style="vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9b39030cc89b4c7d8f59458fc8ad4f17" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.7._Metagenomi_will_and_will_ensure"></a><font style="font-weight: bold;">12.3.7.</font></td>
            <td style="vertical-align: top;">
              <div>Metagenomi will, and will ensure that its Affiliates, Sublicensees, and Subcontractors, obtain agreements from any and all Persons involved in or performing any Development by or on behalf of Metagenomi that assign such Persons&#8217; rights,
                title, and interests in and to any Licensed Technology to Metagenomi prior to any such person performing such activities.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zeaab06ac944b4f6092b988b54aa8005b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.8._Metagenomi_will_and_will_ensure"></a><font style="font-weight: bold;">12.3.8.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will, and will ensure that its Affiliates, comply with Applicable Law in connection with the performance of its and its Affiliates&#8217; activities under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z6694eabccc4449abac05f871249a9ada" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.9._Metagenomi_will_not_and_will_en"></a><font style="font-weight: bold;">12.3.9.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will not, and will ensure that its Affiliates will not, take any action or enter into any agreement with any Third Party that conflicts with or in any way relinquishes or otherwise diminishes the
                rights granted to Ionis under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">49</font></div>
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          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
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          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.10._In_performing_under_this_Agreem"></a><font style="font-weight: bold;">12.3.10.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">In performing under this Agreement, Metagenomi and its Affiliates agree to comply with all applicable anti-corruption laws, including the Foreign Corrupt Practices Act of 1977, as amended from time-to-time;
                the anti-corruption laws of the Territory; and all laws enacted to implement the Organization for Economic Cooperation and Development Convention on Combating Bribery of Foreign Officials in International Business Transactions.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z7594d59b7d85442ab781c1f83225b8d9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.11._Metagenomi_will_not_directly_or"></a><font style="font-weight: bold;">12.3.11.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will not directly or indirectly offer or pay, or authorize such offer or payment of, any money, or transfer anything of value, to improperly seek to influence: (a) any elected or appointed
                government official (e.g., a member of a ministry of health); (b) any employee or person acting for or on behalf of a Governmental Authority; (c) any political party officer, employee, or person acting for or on behalf of a political party
                or candidate for public office; (d) an employee or person acting for or on behalf of a public international organization; or (e) any person otherwise categorized as a government official under local law.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z718348c0ad8b4bab838321b30adb24f6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.12._Neither_Metagenomi_nor_its_Affi"></a><font style="font-weight: bold;">12.3.12.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Neither Metagenomi nor its Affiliates will export, transfer, or sell any Licensed Product to any country or territory except in compliance with Applicable Law.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8ed63d98f8de4ebc80d61c8f429487da" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.13._Metagenomi_will_not_to_Metagen"></a><font style="font-weight: bold;">12.3.13.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will not, to Metagenomi&#8217;s Knowledge, engage directly or indirectly, in any capacity in connection with this Agreement any Person who either has been debarred by the FDA, is the subject of a
                conviction described in Section 306 of the FD&amp;C Act or is subject to any such similar sanction. Metagenomi will inform Ionis in writing promptly if it or any Person engaged by Metagenomi or any of its Affiliates who is performing
                services under this Agreement or any ancillary agreements is debarred or is the subject of a conviction described in Section 306 of the FD&amp;C Act, or if any action, suit, claim, investigation or legal or administrative proceeding is
                pending or, to Metagenomi&#8217;s Knowledge, is threatened, relating to the debarment or conviction of Metagenomi, any of its Affiliates or any such Person performing services hereunder or thereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z264b193811e14edf86c174c119be6c62" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.3.14._Metagenomi_will_not_and_will_c"></a><font style="font-weight: bold;">12.3.14.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Metagenomi will not, and will cause its Affiliates and Sublicensees not to, use or practice the Ionis Background Technology, including the Ionis Proprietary Toolbox of Chemical Modifications, except in
                accordance with this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z18cd238aea3c49b09d54a66754fd26bf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.4._Additional_Representations_of_Ioni"></a><a name="z_bookmark125"></a><font style="font-weight: bold;">12.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Additional Representations of Ionis</font>. As of each Ionis IP Option Effective Date, Ionis represents and warrants to Metagenomi that, except as set forth on <u>Schedule
                  12.4</u> (Ionis Disclosure Schedule) (which schedule may be updated each time a Proposed Metagenomi Target becomes a Metagenomi Target):</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z547e1fb739bd4d4fa2d94145c18182a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.1._To_Ionis_Knowledge_the_practic"></a><font style="font-weight: bold;">12.4.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">To Ionis&#8217; Knowledge, the practice of the Ionis Background Technology as contemplated by this Agreement will not (a) constitute misappropriation of any Know-How of any Third Party, or (b) infringe any Patent
                Rights of any Third Party.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb422ba0026e3400c841072636408a0c0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.2._Ionis_is_the_owner_or_licensee"></a><font style="font-weight: bold;">12.4.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis is the owner, or licensee, of all Ionis Background Technology, all of which is free and clear of any liens, charges, restrictions, and encumbrances (other than licenses granted to Third Parties that are
                not inconsistent with the options, rights, and licenses granted to Metagenomi hereunder), and neither any assignment, license, sublicense, or other grant of any interest in or options to the Ionis Background Technology granted by Ionis or
                its Affiliates to any Third Party, nor any assignment, license, sublicense, or other grant of any interest in or options to the Ionis Background Technology granted by any Third Party to Ionis or its Affiliates conflicts with the options,
                rights, and licenses granted to Metagenomi hereunder, and Ionis is entitled to grant all rights and licenses under the Ionis Background Technology that it purports to grant to Metagenomi under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">50</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z926c49da303142078e171aa5535617fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.3._The_Ionis_Background_Technology_"></a><font style="font-weight: bold;">12.4.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The Ionis Background Technology have not been created pursuant to, and are not subject to, any funding agreement with any Governmental Authority or any Third Party, and are not subject to the requirements of
                the Bayh-Dole Act or any similar provision of any Applicable Law.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z973ecf24f3bc4b56831e43cd20f373db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.4._To_Ionis_Knowledge_no_Third_Pa"></a><font style="font-weight: bold;">12.4.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">To Ionis&#8217; Knowledge, no Third Party has infringed, misappropriated, or otherwise violated, or is currently infringing, misappropriating, or otherwise violating any Ionis Background Technology in a manner that
                would be reasonably likely to adversely affect Metagenomi, and neither Ionis nor its Affiliates have brought any claim or sent any notice alleging any such infringement, misappropriation, or violation.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3f45da9ca2ca45b899fc21d82d83211e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.5._There_are_no_judgments_or_settle"></a><font style="font-weight: bold;">12.4.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">There are no judgments or settlements against Ionis or any of its Affiliates, any pending or, to Ionis&#8217; Knowledge, threatened claims or litigation in writing, or written offers for Ionis to acquire or license
                any Third Party Intellectual Property Rights, in each case, in connection with the Ionis Background Technology or the practice thereof, or relating to the transactions contemplated by this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zeff176d2a3004cbba3db498c976bc739" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.4.6._Ionis_has_not_employed_and_has_"></a><font style="font-weight: bold;">12.4.6.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis has not employed (and has not used a Subcontractor that has employed) any Person debarred by the FDA (or subject to a similar sanction of EMA or foreign equivalent), or any Person that is the subject of
                an FDA debarment investigation or proceeding (or similar proceeding of EMA or foreign equivalent), in any capacity in connection with this Agreement or the Ionis Background Technology.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcdcc88b0e99e4e90b2636f3817defb3b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.5._Covenants_of_Ionis._Ionis_covenant"></a><font style="font-weight: bold;">12.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Covenants of Ionis</font>. Ionis covenants to Metagenomi as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z1b483d3054854f33b9cd7361ee21fa50" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.1._Neither_Ionis_nor_any_of_its_Aff"></a><font style="font-weight: bold;">12.5.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Neither Ionis nor any of its Affiliates will effect any corporate restructuring or enter into any new agreement or otherwise obligate itself to any Third Party, in each case, in a manner that conflicts with
                or otherwise adversely affects the options, rights, and licenses granted to Metagenomi hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z9ad7b32307d04b6bbd5408b69f91ed95" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.2._Ionis_will_and_will_ensure_that"></a><font style="font-weight: bold;">12.5.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will, and will ensure that its Affiliates, comply with all Applicable Law in connection with the performance of its and its Affiliates&#8217; activities under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="zb10c6c53995143e8bb3f6dd721f2af71" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.3._Ionis_will_not_and_will_ensure_"></a><font style="font-weight: bold;">12.5.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will not, and will ensure that its Affiliates will not, take any action or enter into any agreement with any Third Party that conflicts with or in any way relinquishes or otherwise diminishes the rights
                granted to Metagenomi under this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb8459fa75ca34a7fac259da176bae599" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.4._In_performing_under_this_Agreeme"></a><font style="font-weight: bold;">12.5.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">In performing under this Agreement, Ionis and its Affiliates agree to comply with all applicable anti-corruption laws, including the Foreign Corrupt Practices Act of 1977, as amended from time-to-time; the
                anti-corruption laws of the Territory; and all laws enacted to implement the Organization for Economic Cooperation and Development Convention on Combating Bribery of Foreign Officials in International Business Transactions.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8335db5ac9ea470b879091e611b53d9e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.5._Ionis_will_not_directly_or_indir"></a><font style="font-weight: bold;">12.5.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will not directly or indirectly offer or pay, or authorize such offer or payment of, any money, or transfer anything of value, to improperly seek to influence: (a) any elected or appointed government
                official (e.g., a member of a ministry of health); (b) any employee or person acting for or on behalf of a Governmental Authority; (c) any political party officer, employee, or person acting for or on behalf of a political party or
                candidate for public office; (d) an employee or person acting for or on behalf of a public international organization; or (e) any person otherwise categorized as a government official under local law.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54pt;"><br>
              </td>
              <td style="width: 36.05pt; vertical-align: top;"><font style="font-weight: bold;">12.5.6.</font></td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">Neither Ionis nor its Affiliates will export, transfer, or sell any Licensed Product to any country or territory except in compliance with Applicable Law.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">51</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z375666836103472d897fafd9ca8eb723" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.7._Ionis_will_not_to_Ionis_Knowle"></a><font style="font-weight: bold;">12.5.7.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will not, to Ionis&#8217; Knowledge, engage directly or indirectly, in any capacity in connection with this Agreement any Person who either has been debarred by the FDA, is the subject of a conviction
                described in Section 306 of the FD&amp;C Act or is subject to any such similar sanction. Ionis will inform Metagenomi in writing promptly if it or any Person engaged by Ionis or any of its Affiliates who is performing services under this
                Agreement or any ancillary agreements is debarred or is the subject of a conviction described in Section 306 of the FD&amp;C Act, or if any action, suit, claim, investigation or legal or administrative proceeding is pending or, to Ionis&#8217;
                Knowledge, is threatened, relating to the debarment or conviction of Ionis, any of its Affiliates or any such Person performing services hereunder or thereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze685eaf94bb548fd892610fe6f9d3991" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z12.5.8._Ionis_will_not_and_will_cause_i"></a><font style="font-weight: bold;">12.5.8.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Ionis will not, and will cause its Affiliates not to, use or practice the Licensed Technology, except in accordance with this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="za4549437553743c0a1018a9516949379" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z12.6._Warranty_Disclaimer._EXCEPT_AS_OTH"></a><a name="z_bookmark126"></a><font style="font-weight: bold;">12.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Warranty Disclaimer</font>. EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER
                EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED WARRANTIES OF TITLE, NON-INFRINGEMENT, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE. IN PARTICULAR, IONIS DOES NOT MAKE ANY REPRESENTATION OR EXTEND ANY WARRANTY THAT THE LICENSED SYSTEMS OR
                LICENSED PRODUCTS WILL BE SUCCESSFULLY DEVELOPED OR COMMERCIALIZED HEREUNDER.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="text-align: center; font-weight: bold;"><a name="Article_13__Indemnification_Limitation_"></a><a name="z_bookmark127"></a>Article 13</div>
      <div style="text-align: center; font-weight: bold;">Indemnification; Limitation of Liability; Insurance</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf46b01172e284e49b38d7efec8221c96" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.1._Indemnification_of_Metagenomi_by_I"></a><a name="z_bookmark128"></a><font style="font-weight: bold;">13.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Indemnification of Metagenomi by Ionis</font>. Subject to <u>Section 13.4</u> (Conditions to Indemnification), Ionis will defend, indemnify, and hold harmless Metagenomi and
                its Affiliates, Sublicensees, Subcontractors, and their respective employees, officers, and directors (&#8220;<font style="font-weight: bold;">Metagenomi Indemnitees</font>&#8221;) from and against any and all liability, damage, loss, cost, or expense
                of any nature (including reasonable attorney&#8217;s fees and litigation expenses) (&#8220;<font style="font-weight: bold;">Losses</font>&#8221;) incurred or imposed upon the Metagenomi Indemnitees in connection with any claims, suits, actions, demands,
                proceedings, causes of action, or judgments resulting from a Third Party claim (&#8220;<font style="font-weight: bold;">Third Party Claims</font>&#8221;) arising out of or relating to:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4ea65dbba7b54a9ca588a86686b24ec8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.1.1._the_Exploitation_of_any_Licensed"></a><a name="z_bookmark129"></a><font style="font-weight: bold;">13.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the Exploitation of any Licensed System or Licensed Product by or on behalf of any Ionis Indemnitee other than (a) claims by one or more Third Parties relating to patent infringement arising out of the
                practice of the Licensed Patent Rights in accordance with this Agreement, (b) claims by Third Parties relating to misappropriation of trade secrets or other Intellectual Property Rights arising out of the practice of the Licensed Know-How
                in accordance with this Agreement, or (c) Losses shared pursuant to <u>Section 13.3</u> (Losses for the Co-Co Products);</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd6bbe0e916804c3c8b7bc14e0f3ec471" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.1.2._the_breach_by_any_Ionis_Indemnit"></a><font style="font-weight: bold;">13.1.2.</font></td>
            <td style="vertical-align: top;">
              <div>the breach by any Ionis Indemnitee of any term of this Agreement; or</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z15cb5a1ce6ab455e9e529eb654148efe" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.1.3._the_negligence_or_willful_miscon"></a><a name="z_bookmark130"></a><font style="font-weight: bold;">13.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the negligence or willful misconduct of any Ionis Indemnitee except, in each case (<u>Section</u>&#160;<u>13.1.1</u> through <u>Section 13.1.3</u>), to the extent that any such claim results or arises from a
                matter for which Metagenomi is obligated to indemnify Ionis under <u>Section 13.2</u> (Indemnification of Ionis by Metagenomi).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">52</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za8e168de9da044f7807613511d6a5f8c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.2._Indemnification_of_Ionis_by_Metage"></a><a name="z_bookmark131"></a><font style="font-weight: bold;">13.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Indemnification of Ionis by Metagenomi</font>. Subject to <u>Section 13.4</u> (Conditions to Indemnification), Metagenomi will defend, indemnify, and hold harmless Ionis and
                its Affiliates, Sublicensees, and Subcontractors, and their respective employees, officers, and directors (&#8220;<font style="font-weight: bold;">Ionis Indemnitees</font>&#8221;) from and against any and all Losses incurred or imposed upon the Ionis
                Indemnitees or any one of them in connection with one or more Third Party Claims arising out of or relating to:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z4281a5143ef240e8abac349d1e5f4bc5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.1._any_claim_that_the_composition_o"></a><a name="z_bookmark132"></a><font style="font-weight: bold;">13.2.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">any claim that the composition of matter [***] of a Gene Editing protein to edit gene targets (but not to edit the Collaboration Targets specifically) infringes or misappropriates any issued Patent Right or
                other Intellectual Property Right owned or possessed by any Third Party;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd8a01552e5554264bf8d3a315a354eef" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.2._the_Exploitation_of_any_Licensed"></a><font style="font-weight: bold;">13.2.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the Exploitation of any Licensed System that is included within a Licensed Product by any Metagenomi Indemnitee, other than Losses shared pursuant to <u>Section 13.3</u> (Losses for the Co-Co Products) and
                any amounts [***];</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zde492959fc284fe0a2c8d9c874996054" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.3._the_Exploitation_of_any_Licensed"></a><font style="font-weight: bold;">13.2.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the Exploitation of any Licensed System or Licensed Product by or on behalf of any Metagenomi Indemnitee prior to the Effective Date and after termination of this Agreement;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z216a3a6db02f4cf1b2c4ba98966390da" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.4._the_Exploitation_of_any_Metageno"></a><font style="font-weight: bold;">13.2.4.</font></td>
            <td style="vertical-align: top;">
              <div>the Exploitation of any Metagenomi Product by or on behalf of any Metagenomi Indemnitee;</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6150219669f2412d9ddd0835bb3e61f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.5._the_breach_by_any_Metagenomi_Ind"></a><font style="font-weight: bold;">13.2.5.</font></td>
            <td style="vertical-align: top;">
              <div>the breach by any Metagenomi Indemnitee of any term of this Agreement; or</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb08f7527f8964bd0afa69f55e6971764" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z13.2.6._the_negligence_or_willful_miscon"></a><a name="z_bookmark133"></a><font style="font-weight: bold;">13.2.6.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">the negligence or willful misconduct of any Metagenomi Indemnitee except, in each case (<u>Section 13.2.1</u> through <u>Section 13.2.6</u>), to the extent that any such claim results or arises from a matter
                for which Ionis is obligated to indemnify Metagenomi under <u>Section 13.1</u> (Indemnification of Metagenomi by Ionis).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcf8509e414f643c7af2ec762661d23d4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.3._Losses_for_the_Co-Co_Products._All"></a><a name="z_bookmark134"></a><font style="font-weight: bold;">13.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Losses for the Co-Co Products</font>. All Losses incurred by either Party arising from any Third Party Claim relating to the Exploitation of the Co-Co Products will be shared
                by the Parties pursuant to the Co-Development and Co-Commercialization Agreement; <font style="font-style: italic;">provided </font>that the Parties will not share Losses of a Party or its Affiliates to the extent such Losses are (a)
                caused by a breach of this Agreement by a Party or Affiliate or (b) caused by gross negligence or willful misconduct of a Party or its Affiliate. As will be further set forth in the applicable Co-Development and Co- Commercialization
                Agreement, if either Party learns of any Third Party Claim with respect to Losses covered by this <u>Section 13.3</u> (Losses for the Co-Co Products), such Party will provide the other Party with prompt written notice thereof, and the
                Parties will confer with respect to how to respond to such Third Party Claim and how to handle such Third Party Claim in an efficient manner. In the absence of such an agreement, each Party will have the right to take such action as it
                deems appropriate.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">53</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf48731e5fd8b4043a36c5835d24d20bd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.4._Conditions_to_Indemnification._Any"></a><a name="z_bookmark135"></a><font style="font-weight: bold;">13.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Conditions to Indemnification</font>. Any Person seeking indemnification under this <u>Article 13</u> (Indemnification; Limitation Of Liability; Insurance) (the &#8220;<font style="font-weight: bold;">Indemnitee</font>&#8221;) will give prompt written notice of the indemnity claim to the indemnifying Party and promptly provide a copy to the indemnifying Party of any complaint, summons, or other written or verbal
                notice that the Indemnitee receives in connection with any such claim. An Indemnitee&#8217;s failure to deliver written notice will relieve the indemnifying Party of liability to the Indemnitee under this <u>Article 13</u> (Indemnification;
                Limitation Of Liability; Insurance) only to the extent such delay is prejudicial to the indemnifying Party&#8217;s ability to defend or settle such claim. The indemnifying Party will have the right to assume and control the defense of the
                indemnification claim at its own expense with counsel selected by the indemnifying Party and reasonably acceptable to the Indemnitee; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>,
                that an Indemnitee will have the right to retain its own counsel that is reasonably acceptable to the indemnifying Party, with the fees and expenses to be paid by the indemnifying Party, if representation of such Indemnitee by the counsel
                retained by the indemnifying Party would be inappropriate due to actual or potential differing interests between the Indemnitee and any other party represented by such counsel in such proceedings. The indemnifying Party will act reasonably
                and in good faith with respect to all matters relating to such claim. If the indemnifying Party does not assume the defense of the indemnification claim as described in this <u>Section 13.4</u> (Conditions to Indemnification), then the
                Indemnitee may defend the indemnification claim but will have no obligation to do so. The Indemnitee will not settle or compromise the indemnification claim without the prior written consent of the indemnifying Party, and the indemnifying
                Party will not settle or compromise the indemnification claim in any manner which would have an adverse effect on the Indemnitee&#8217;s interests (including any rights under this Agreement or the scope, validity, or enforceability of any Patent
                Rights, Confidential Information, or other rights licensed to Ionis by Metagenomi hereunder), without the prior written consent of the Indemnitee, which consent, in each case (by the indemnifying Party or the Indemnitee, as the case may
                be), will not be unreasonably withheld, conditioned, or delayed. The Indemnitee will reasonably cooperate with the indemnifying Party at the indemnifying Party&#8217;s expense and will make available to the indemnifying Party all pertinent
                information under the control of the Indemnitee, which information will be subject to <u>Article 11</u> (Confidentiality). The indemnifying Party will not be liable for any settlement or other disposition of the claims by the Indemnitee if
                such settlement is reached without the written consent of the indemnifying Party pursuant to this <u>Section 13.4</u> (Conditions to Indemnification).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z719226a2bb704d76ba77914712367ee9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.5._Limited_Liability._NEITHER_OF_THE_"></a><a name="z_bookmark136"></a><font style="font-weight: bold;">13.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Limited Liability</font>. NEITHER OF THE PARTIES NOR THEIR RESPECTIVE AFFILIATES OR SUBLICENSEES WILL BE ENTITLED TO RECOVER FROM THE OTHER PARTY OR ITS AFFILIATES OR
                SUBLICENSEES ANY SPECIAL, INCIDENTAL, INDIRECT, CONSEQUENTIAL, OR PUNITIVE DAMAGES OR DAMAGES FOR LOSS OF PROFIT, LOST OPPORTUNITY, LOST DATA OR COST OF PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES IN CONNECTION WITH THIS AGREEMENT, ITS
                PERFORMANCE OR LACK OF PERFORMANCE HEREUNDER, WHETHER LIABILITY IS ASSERTED IN CONTRACT, TORT (INCLUDING NEGLIGENCE AND STRICT PRODUCT LIABILITY), INDEMNITY OR CONTRIBUTION, AND IRRESPECTIVE OF WHETHER THAT PARTY OR ANY REPRESENTATIVE OF
                THAT PARTY HAS BEEN ADVISED OF, OR OTHERWISE MIGHT HAVE ANTICIPATED THE POSSIBILITY OF, ANY SUCH LOSS OR DAMAGE, OR ANY LICENSE GRANTED HEREUNDER, EXCEPT TO THE EXTENT THE DAMAGES RESULT FROM (A) A PARTY&#8217;S WILLFUL MISCONDUCT OR GROSS
                NEGLIGENCE UNDER THIS AGREEMENT, (B) A BREACH OF THE OBLIGATIONS OF A PARTY UNDER <u>ARTICLE 11</u> (CONFIDENTIALITY) OR UNDER <u>SECTION 3.6</u> (EXCLUSIVITY), OR (C) AMOUNTS REQUIRED TO BE PAID AS PART OF A CLAIM FOR WHICH A PARTY
                PROVIDES INDEMNIFICATION UNDER <u>ARTICLE 13</u> (INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z35866fe327654d1093a10e440633bbf4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z13.6._Insurance_Obligations._Each_Party_"></a><a name="z_bookmark137"></a><font style="font-weight: bold;">13.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Insurance Obligations</font>. Each Party will, at its own expense, procure and maintain during the Term and for a period of [***] thereafter, insurance policies, including
                product liability insurance when applicable, adequate to cover its obligations hereunder and that are consistent with normal business practices of prudent companies similarly situated. Such insurance will not be construed to create a limit
                of a Party&#8217;s liability with respect to its indemnification obligations under this <u>Article&#160;13</u> (Indemnification; Limitation of Liability; Insurance). Each Party will provide the other Party with written evidence of such insurance.
                Notwithstanding any provision to the contrary set forth in this Agreement, Ionis may self-insure, in whole or in part, the insurance requirements described above.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">54</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="Article_14__Term_and_Termination"></a><a name="z_bookmark138"></a>Article 14</div>
      <div style="text-align: center; font-weight: bold;">Term and Termination</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z39d0ccee6cac42368b196e36a6067e4c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z14.1._Term._This_Agreement_will_commence"></a><a name="z_bookmark139"></a><font style="font-weight: bold;">14.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Term</font>. This Agreement will commence on the Effective Date and, unless otherwise terminated pursuant to <u>Section 14.2</u> (Termination), will continue (a) with respect
                to the Ionis Programs, on an Ionis Product-by-Ionis Product and country-by-country basis until the expiration of all applicable Royalty Terms for an Ionis Product in a country, (b) with respect to the Co-Co Programs for which Metagenomi has
                not exercised its Opt-Out Right in accordance with <u>Section 5.4</u> (Metagenomi Opt- Out), on a Co-Co Program-by-Co-Co Program basis until the Parties cease all Exploitation for the Co-Co Products that are the subject to such Co-Co
                Program, and (c) with respect to the Metagenomi Products, on a Metagenomi Product-by-Metagenomi Product and country-by-country basis until the expiration of the Metagenomi Royalty Term for a Metagenomi Product in a country (the &#8220;<font style="font-weight: bold;">Term</font>&#8221;). On a Licensed Product-by-Licensed Product and country-by-country basis, effective upon the expiration of the Royalty Term for a Licensed Product in a country (but not upon any earlier termination
                of this Agreement for any reason), the licenses granted to Ionis will each become fully paid-up, royalty-free, irrevocable, and perpetual in such country with respect to such Licensed Product. On a Metagenomi Product-by-Metagenomi Product
                and country-by-country basis, effective upon the expiration of the Metagenomi Royalty Term for a Metagenomi Product in a country (but not upon any earlier termination of this Agreement for any reason), the licenses granted to Metagenomi
                will each become fully paid-up, royalty-free, irrevocable, and perpetual in such country with respect to such Metagenomi Product.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z181dbdd35b9442d6a585f8fa216f5a8c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z14.2._Termination._This_Agreement_may_be"></a><a name="z_bookmark140"></a><font style="font-weight: bold;">14.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Termination</font>. This Agreement may be terminated as follows:</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z56de17069db84203866b6f92b91999df" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.2.1._Termination_for_Convenience_by_I"></a><font style="font-weight: bold;">14.2.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Termination for Convenience by Ionis</font>. Ionis may terminate this Agreement (either in its entirety or on a Licensed Product-by-Licensed Product basis), for convenience by
                providing written notice of its intent to terminate to Metagenomi, in which case, such termination will be effective 90 days after Metagenomi&#8217;s receipt of such written notice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z8ea79d76a3ae4b5488feafae8167d928" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.2.2._Termination_for_Material_Breach."></a><a name="z_bookmark141"></a><font style="font-weight: bold;">14.2.2.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Termination for Material Breach</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf2bf6a1d95d7475fae649866664c4e64" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Ionis_Right_to_Terminate._If_Metage"></a><a name="z_bookmark142"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Ionis&#8217; Right to Terminate</font>. If Metagenomi is in material breach of this Agreement, then Ionis may deliver written notice of such material breach to Metagenomi. If the
                breach is curable, then Metagenomi will have [***] following its receipt of such written notice to cure such breach (except to the extent such breach involves the failure to make a payment when due, in which case such breach must be cured
                within [***] following Metagenomi&#8217;s receipt of such written notice). If Metagenomi fails to cure such breach within such [***] or [***] period, as applicable, or the breach is not subject to cure, then Ionis may terminate this Agreement
                solely with respect to those Licensed Products to which such material breach relates, or in its entirety if such material breach relates to all Licensed Products, by providing written notice to Metagenomi, in which case, this Agreement will
                terminate on the date on which Metagenomi receives such written notice; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, that if (A) the relevant breach does not involve Metagenomi&#8217;s
                failure to make a payment when due and is curable, but not reasonably curable within [***], and (B) Metagenomi is making a <font style="font-style: italic;">bona fide </font>effort to cure such breach, then Ionis&#8217; right to terminate this
                Agreement on account of such breach will be suspended for up to an additional [***] so long as Metagenomi is continuing to make such <font style="font-style: italic;">bona fide </font>effort to cure such breach. If such breach is
                successfully cured during the applicable cure period, then Ionis will no longer have the right to terminate this Agreement on account of such breach.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">55</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z94649eea9f2d4ece882f9a5c5a557546" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Metagenomis_Right_to_Terminate._If_"></a><a name="z_bookmark143"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Metagenomi&#8217;s Right to Terminate</font>. If Ionis is in material breach of this Agreement, then Metagenomi may deliver written notice of such material breach to Ionis. If the
                breach is curable, then Ionis will have [***] following its receipt of such written notice to cure such breach (except to the extent such breach involves the failure to make a payment when due, in which case such breach must be cured within
                [***] following Ionis&#8217; receipt of such written notice). If Ionis fails to cure such breach within the [***] or [***] period, as applicable, or the breach is not subject to cure, then Metagenomi may terminate this Agreement in its entirety
                by providing written notice to Ionis, in which case this Agreement will terminate on the date on which Ionis receives such written notice; <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>,
                that if (i) the relevant breach does not involve Ionis&#8217; failure to make a payment when due and is curable, but not reasonably curable within [***], and Ionis is making a <font style="font-style: italic;">bona fide </font>effort to cure
                such breach, then Metagenomi&#8217;s right to terminate this Agreement on account of such breach will be suspended for up to an additional [***] so long as Ionis is continuing to make such <font style="font-style: italic;">bona fide </font>effort


                to cure such breach. If such breach is successfully cured during the applicable cure period, then Metagenomi will no longer have the right to terminate this Agreement on account of such breach. Notwithstanding the foregoing, any license
                granted to Ionis under this Agreement may not be terminated under this <u>Section 14.2.2(b)</u> (Metagenomi&#8217;s Right to Terminate) if (A) the material breach does not involve the failure to make any material and undisputed portion of a
                payment due to Metagenomi under <u>Article 9</u> (Consideration; Financial Terms) and (B) such license is necessary to make, have made, use or sell a Licensed Product for which a Clinical Trial has been Initiated. Termination pursuant to
                this <u>Section 14.2.2(b)</u> (Metagenomi&#8217;s Right to Terminate) will not relieve Ionis from liability and damages to Metagenomi for default, and the Parties agree that if monetary damages are available to Metagenomi as a reasonable remedy
                for any default hereunder, then such monetary remedy will constitute the exclusive remedy for such default in lieu of termination of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb597ed222ff646f7ac04f92f3921c9af" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Disputes_Regarding_Material_Breach._"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Disputes Regarding Material Breach</font>. Notwithstanding the foregoing, if the alleged breaching Party in <u>Section 14.2.2(a)</u> (Ionis&#8217; Right to Terminate) or <u>Section</u>&#160;<u>14.2.2(b)</u>
                (Metagenomi&#8217;s Right to Terminate) disputes in good faith the existence or materiality of any breach, or failure to cure any breach, and provides written notice to the non-breaching Party of such dispute within the relevant cure period, then
                the non-breaching Party will not have the right to terminate this Agreement in accordance with <u>Section 14.2.2(a)</u> (Ionis&#8217; Right to Terminate) or <u>Section&#160;14.2.2(b)</u> (Metagenomi&#8217;s Right to Terminate), as applicable, unless and
                until the relevant dispute has been resolved in accordance with <u>Section 15.1</u> (Dispute Resolution). During the pendency of such dispute, all the terms of this Agreement will remain in effect and the Parties will continue to perform
                all of their respective obligations hereunder.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z57299788fddc4ae595d29b4f09edb44f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.2.3._Termination_for_Insolvency._If_M"></a><font style="font-weight: bold;">14.2.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Termination for Insolvency</font>. If Metagenomi makes an assignment for the benefit of creditors, appoints or suffers appointment of a receiver or trustee over all or
                substantially all of its property, files a petition under any bankruptcy or insolvency act, or has any such petition filed against it that is not discharged within [***] after the filing thereof (each, an &#8220;<font style="font-weight: bold;">Insolvency


                  Event</font>&#8221;), then Ionis may terminate this Agreement in its entirety by providing written notice of its intent to terminate this Agreement to Metagenomi, in which case, this Agreement will terminate on the date on which Metagenomi
                receives such written notice.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z2c5b4d8e1ff0408ca02b972cb94414a7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z14.3._Effects_of_Termination._In_the_eve"></a><a name="z_bookmark144"></a><font style="font-weight: bold;">14.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Effects of Termination</font>. In the event of any early termination of this Agreement by a Party pursuant to <u>Section 14.2</u> (Termination), effective as of the effective
                date of termination, the following provisions will apply with respect to the Terminated Products in the Terminated Countries:</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">56</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zbefd86ca9ff0440f9bac0ca95aea2a7f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.1._Wind-Down._During_the_applicable"></a><a name="z_bookmark145"></a><font style="font-weight: bold;">14.3.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Wind-Down</font>. During the applicable termination notice period, unless otherwise agreed by the Parties, the Parties will begin to wind-down their respective activities
                under this Agreement to the extent related to the Terminated Products in the Terminated Countries. The JSC will coordinate the wind-down of each Party&#8217;s efforts under this Agreement with respect to the Terminated Products in the Terminated
                Countries, or, if the JSC has disbanded, then the Parties will establish an appropriate committee to coordinate such wind-down.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zd3d7364f97c94320bc1a30ff25066181" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.2._Termination_of_Rights_and_Licens"></a><font style="font-weight: bold;">14.3.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Termination of Rights and Licenses</font>. Other than as expressly set forth herein, including those provisions that this Agreement expressly provides will survive such
                termination and subject to <u>Section 14.3.8</u> (Sublicense Survival), all rights and licenses granted from one Party to the other hereunder will immediately terminate with respect to the Terminated Products in the Terminated Countries; <font style="font-style: italic;">provided </font>that such licenses will continue as necessary for the Parties to complete the orderly wind-down of their activities under this Agreement in accordance with Applicable Law and as otherwise
                required in accordance with <u>Section 14.3.1</u> (Wind-Down).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zce9ea58dae6c4dc5849b8e7098c58b95" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.3._Termination_of_Payment_Obligatio"></a><font style="font-weight: bold;">14.3.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Termination of Payment Obligations</font>. All payment obligations with respect to the Terminated Products in the Terminated Countries hereunder will terminate, other than
                those that are accrued and unpaid as of the effective date of such termination. For any payment obligations that are accrued and unpaid as of the effective date of termination, an invoice must be provided no later than [***] after the
                effective date of termination.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zf80ecc9b6ee340b2bdfa699d431a9858" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.4._Sell-Off_Right._For_a_period_not"></a><font style="font-weight: bold;">14.3.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sell-Off Right</font>. For a period not to exceed [***] following the effective date of termination, Ionis will have the right to sell or otherwise dispose of the Terminated
                Products in the Terminated Countries on hand at the time of such termination or in the process of Manufacturing; <font style="font-style: italic;">provided </font>that any revenue obtained from such disposal will be treated as Net Sales
                and the provisions of <u>Article 9</u> (Consideration; Financial Terms) will apply to such Net Sales and, if such sales result in the achievement of any Ionis Product Sales Milestone Event, then the applicable Ionis Product Sales Milestone
                Payment will be payable.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3a36a1541d6d43b68b869d61ae88ce61" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.5._Assignment_of_Regulatory_Submiss"></a><font style="font-weight: bold;">14.3.5.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Assignment of Regulatory Submissions</font>. Except with respect to any termination by Ionis under <u>Section 14.2.2(a)</u> (Ionis&#8217; Right to Terminate), Ionis will, as
                promptly as practicable, transfer to Metagenomi possession and ownership of all Regulatory Approvals solely relating to the Exploitation of any Terminated Product in the Terminated Countries.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zdfe81721f1124d548894f4cdb930bfea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.6._Reversion_for_Terminated_Product"></a><font style="font-weight: bold;">14.3.6.</font></td>
            <td style="vertical-align: top;">
              <div><font style="font-weight: bold;">Reversion for Terminated Products other than Combination Products</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z6699131cf6b44b818b8b4e9ffc8dbad7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_Reversion_License_Grant._Upon_Metage"></a><a name="z_bookmark146"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Reversion License Grant</font>. Upon Metagenomi&#8217;s written request no later than [***] following the effective date of termination and agreement by the Parties of the
                applicable royalty rate pursuant to <u>Section 14.3.6(c)</u> (Reversion Royalties), Ionis will grant and agrees to grant to Metagenomi, an exclusive, royalty-bearing (solely as provided in <u>Section 14.3.6(c)</u> (Reversion Royalties)),
                right and license, with the right to grant sublicenses through multiple tiers, under Patent Rights and Know-How Controlled by Ionis or its Affiliates to the extent such Patent Rights or Know-How are actually being used on the date of such
                termination by the Parties in the Development, Commercialization, or other Exploitation of the Terminated Products in the Terminated Countries as such Terminated Products exist as of the effective date of termination, solely to Exploit such
                Terminated Products in the Terminated Countries; <font style="font-style: italic;">provided </font>that, if any such Terminated Products are Combination Products, then such license will not include any license or other rights with respect
                to any Other Product that is Covered by Patent Rights Controlled by Ionis or any of its Affiliates and Metagenomi will not obtain a license to any such Other Product other than pursuant to <u>Section 14.3.7</u> (Reversion for Certain
                Combination Products) (such license grant, the &#8220;<font style="font-weight: bold;">Reversion License</font>&#8221;).</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">57</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zeb05f7e3c14c4fc8be62e5ab9c82b07a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Third_Party_Reversion_IP._With_respe"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Third Party Reversion IP</font>. With respect to any Patent Rights or Know-How that are the subject of the Reversion License that are in-licensed by Ionis from Third Parties,
                Ionis will notify Metagenomi of such Patent Rights or Know-How that are sublicensable to Metagenomi under the Reversion License (which notice will describe the terms and conditions of any Third Party agreements that are applicable to the
                grant to Metagenomi of the Reversion Licenses under such Patent Rights or Know-How (any such agreement, a &#8220;<font style="font-weight: bold;">Reversion IP In-License Agreement</font>&#8221;), including applicable payment terms). If Metagenomi
                elects to receive a sublicense under any Reversion IP In-License Agreement, then Metagenomi will notify Ionis in writing and Metagenomi will be responsible for (i) making all payments (including royalties, milestones, and other amounts)
                that are payable by Ionis to the Third Parties under each Reversion IP In-License Agreement with respect to and allocable to the Patent Rights and Know-How that are the subject of the Reversion License and arising out of the Exploitation of
                the Terminated Products in the Terminated Countries by making such payments directly to Ionis and, in each instance, Metagenomi will make the requisite payments to Ionis and provide the necessary reporting information to Ionis in sufficient
                time to enable Ionis to comply with its obligations under each Reversion IP In-License Agreement, and (ii) complying with any other obligations included in each Reversion IP In-License Agreement that are applicable to the grant to
                Metagenomi of the Reversion License under the applicable Patent Rights or Know-How (<font style="font-style: italic;">provided </font>that Ionis has notified Metagenomi of such obligations), and the granting by Metagenomi of a sublicense
                under the Reversion Licenses will not relieve Metagenomi of its obligations under subclauses (i) and (ii).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z961dbf9a961a461c8a6fb507ceef487a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_Reversion_Royalties._The_licenses_gr"></a><a name="z_bookmark147"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Reversion Royalties</font>. The licenses granted to Metagenomi in <u>Section 14.3.6(a)</u> (Reversion License Grant) will be royalty-bearing, and Metagenomi will pay Ionis,
                on a Calendar Quarter basis, the royalty rates that are agreed to by the Parties at the time of Metagenomi&#8217;s written request delivered pursuant to <u>Section 14.3.6(a)</u> (Reversion License Grant). With respect to the royalty rates to be
                agreed to by the Parties pursuant to this <u>Section 14.3.6(c)</u> (Reversion Royalties), the Parties will take into account, among other things, (i) [***], (ii) [***], (iii) [***], and (iv) [***], and if the Parties have not reached
                agreement on such financial terms within [***] after such effective date of termination, then either Party may refer such matter for resolution pursuant to <u>Section 15.1.3</u> (Expedited Dispute Resolution).</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zeec56ce701984de3b64d09e1ffddd20d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.7._Reversion_for_Certain_Combinatio"></a><a name="z_bookmark148"></a><font style="font-weight: bold;">14.3.7.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Reversion for Certain Combination Products</font>. If (a) any of the Terminated Products are Combination Products that are required, by the approved labeling for such
                Terminated Product, to be promoted as a Combination Product and the Other Product for such Terminated Product is exclusively Controlled by Ionis, such that Metagenomi is not able to otherwise acquire such Other Product, and (b) there is no
                approved label regarding the promotion of the Terminated Product that is not a Combination Product (any such Terminated Product meeting the requirements of (a) and (b), a &#8220;<font style="font-weight: bold;">Terminated Combination Products</font>&#8221;),


                then upon Metagenomi&#8217;s written request no later than [***] following the effective date of termination for such Terminated Combination Products, the Parties will enter into good faith negotiations for up to [***] regarding the grant of a
                non-exclusive, royalty-bearing right and license, with the right to grant sublicenses through multiple tiers, under Patent Rights and Know-How Controlled by Ionis or its Affiliates to the extent such Patent Rights or Know-How are actually
                being used on the date of such termination by the Parties in the Development, Commercialization, or other Exploitation of the Terminated Combination Products in the Terminated Countries as such Terminated Combination Products exist as of
                the effective date of termination, solely to Exploit such Terminated Combination Products in the Terminated Countries.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">58</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zf2aba9d8bb5b4e0db457ba20d2b38f4a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z14.3.8._Sublicense_Survival._Any_sublice"></a><a name="z_bookmark149"></a><font style="font-weight: bold;">14.3.8.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Sublicense Survival</font>. Any sublicense granted hereunder by Ionis will, at the Sublicensee&#8217;s option, survive such termination on the condition that the relevant
                Sublicensee is not in material breach of any of its obligations under such sublicense. In order to effect this provision, at the request of the Sublicensee, Metagenomi will enter into a direct license with the Sublicensee on terms that are
                substantially the same terms as the applicable terms of this Agreement; <font style="font-style: italic;">provided </font>that Metagenomi will not be required to undertake obligations in addition to those required by this Agreement, and
                Metagenomi&#8217;s rights under such direct license will be consistent with its rights under this Agreement, taking into account the scope of the license granted under such direct license.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z99d0db3ed96a4c72a96454351cc80f24" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z14.4._Confidential_Information._Upon_the"></a><a name="z_bookmark150"></a><font style="font-weight: bold;">14.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Confidential Information</font>. Upon the expiration or termination of this Agreement with respect to a Terminated Product in a Terminated Country, the Receiving Party will
                return (or, as directed by the Disclosing Party, destroy) all Confidential Information of the Disclosing Party related to such Terminated Product in such Terminated Country to the Disclosing Party that is in the Receiving Party&#8217;s possession
                or control (other than any Confidential Information required to continue to exercise a Party&#8217;s rights that survive such expiration or termination of this Agreement); <font style="font-style: italic;">provided</font>, <font style="font-style: italic;">however</font>, copies may be retained and stored solely for the purpose of determining a Party&#8217;s obligations under this Agreement, subject to the non-disclosure and non-use obligation under <u>Article 11</u>
                (Confidentiality). In addition, the Receiving Party will not be required to return or destroy Confidential Information contained in any computer system back-up records made in the ordinary course of business.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z0cd5f02371d7430a9f16270e13fe4655" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top; font-weight: bold;">14.5.</td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><a name="z14.5._Surviving_Provisions._Subject_to_t"></a><a name="z_bookmark151"></a><font style="font-weight: bold;">Surviving Provisions</font>. Subject to the other terms and conditions regarding the
                termination and survival of obligations under this Agreement in the event of expiration or termination of this Agreement, upon expiration or termination of this Agreement, all provisions of this Agreement will cease to have any effect,
                except that the following provisions will survive any such expiration or termination for any reason for the period of time specified therein, or if not specified, then they will survive indefinitely: <u>Section 2.5.1</u> (Reimbursement by
                Ionis) (solely with respect to obligations accrued, but not yet paid, as of the effective date of termination of this Agreement); <u>Section 3.1.3</u> (Unblocking License); <u>Section 3.2.2</u> (Unblocking License); <u>Section 3.5</u>
                (No Implied Licenses); <u>Section 9.4</u> (Ionis Product Milestone Payments), <u>Section 9.6</u> (Ionis Product Royalty Payments), <u>Section 9.9</u> (Payment Obligations Under Certain In-License Agreements), and <u>Section 9.10</u>
                (Metagenomi Product Economics) (in each case, solely with respect to obligations accrued, but not yet paid, as of the effective date of expiration or termination of this Agreement); <u>Section 9.11</u> (Other Payments); <u>Section 9.12</u>
                (Right to Offset); <u>Section 9.13</u> (Records and Audits) (solely for [***] after termination or expiration of this Agreement); <u>Section 9.14</u> (Currency of Payment; Non- Refundable Payments) through <u>Section 9.17</u>
                (Withholding Taxes); <u>Section 10.1.1</u> (Background Intellectual Property); <u>Section 10.1.2</u> (By Inventorship); <u>Section 10.2</u> (Patent Prosecution) (solely with respect to Joint Collaboration Patent Rights); <u>Section 10.3</u>
                (Patent Enforcement) (solely with respect to Joint Collaboration Patent Rights); <u>Section 11.1</u> (Confidential Information) through <u>Section 11.4</u> (Publication Announcements and Subsequent Disclosures); <u>Section 12.6</u>
                (Warranty Disclaimer); <u>Section 13.1</u> (Indemnification of Metagenomi by Ionis) through <u>Section 13.5</u> (Limited Liability); <u>Section 13.6</u> (Insurance Obligations) (solely for [***] after expiration or termination of this
                Agreement); <u>Section 14.1</u> (Term) (solely in the event of expiration and with respect to the last two sentences); <u>Section 14.3</u> (Effects of Termination); <u>Section 14.4</u> (Confidential Information); this <u>Section 14.5</u>
                (Surviving Provisions); <u>Article 15</u> (Miscellaneous); and <u>Appendix 1</u> (Definitions) (as applicable). Termination or expiration of this Agreement (either in its entirety or with respect to one or more Licensed Products) will not
                relieve either Party of any liability that accrued hereunder prior to the effective date of such termination or expiration, preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity with
                respect to any breach of this Agreement nor prejudice any rights that will have accrued to the benefit of any Party prior to such termination or expiration. The remedies provided in this <u>Article 14</u> (Term and Termination) are not
                exclusive of any other remedies a Party may have in law or equity.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">59</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="z_bookmark152"></a><a name="z_TOC_250002"></a>Article 15 </div>
      <div style="text-align: center; font-weight: bold;">Miscellaneous</div>
      <div style="text-align: center;">&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z3802943e05c44f7db9f1ef00ab3008fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_bookmark153"></a><a name="z_TOC_250001"></a><font style="font-weight: bold;">15.1.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Dispute Resolution</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zc4cd38de2df94eeba3c4f4afc7b9be75" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z15.1.1._Escalation._In_the_event_of_any_"></a><font style="font-weight: bold;">15.1.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Escalation</font>. In the event of any dispute, claim, controversy, or cause of action asserted by a Party against the other Party or by the Metagenomi Indemnitees against
                Ionis or by the Ionis Indemnitees against Metagenomi arising out of or related to this Agreement or performance of this Agreement (other than matters within the purview of the JSC, which will be resolved as set forth in <u>Section 4.6</u>
                (Decision-Making)) (a &#8220;<font style="font-weight: bold;">Claim</font>&#8221;), including any alleged breach of this Agreement or claim for indemnification pursuant to <u>Article 13</u> (Indemnification; Limitation Of Liability; Insurance), such
                Party may, by written notice to the other Party, refer such matter to the Parties&#8217; respective officers designated below for attempted resolution (each, an &#8220;<font style="font-weight: bold;">Executive Officer</font>&#8221;):</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z49978c1f728e4055b32eb5aca2da9efa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 86.95pt;"><br>
            </td>
            <td style="width: 100.8pt; vertical-align: top;">For Ionis:</td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;">Chief Executive Officer (or such other senior executive designated by Ionis for such purpose)</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify;">&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z054eb027a74b4bf59bab6bc4a53b4f9a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 86.95pt;"><br>
            </td>
            <td style="width: 100.85pt; vertical-align: top;">For Metagenomi:</td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;">Chief Executive Officer (or such other senior executive designated by Metagenomi for such purpose)</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="za37bf1c54b2241a5b73acd0fdd5fecea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z15.1.2._Arbitration._Except_as_otherwise"></a><a name="z_bookmark154"></a><font style="font-weight: bold;">15.1.2.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Arbitration</font>. Except as otherwise expressly set forth in this Agreement, if such Executive Officers do not resolve the dispute within [***] after receipt of such
                request, then, either Party may at any time after such [***] period submit such Claim to be finally settled by arbitration administered in accordance with the procedural rules of the American Arbitration Association (the &#8220;<font style="font-weight: bold;">AAA</font>&#8221;) in effect at the time of submission, as modified by this <u>Section 15.1.2</u> (Arbitration) (the &#8220;<font style="font-weight: bold;">Arbitration</font>&#8221;). The Arbitration will be governed by the
                Applicable Law of the State of New York. The Arbitration will be heard and determined by three arbitrators who are retired judges or attorneys with at least 20 years of relevant experience, each of whom will be impartial and independent and
                will not have worked for or on behalf of either Party for at least [***]. Each Party will appoint one arbitrator and the third arbitrator will be selected by the two Party-appointed arbitrators, or, failing agreement within [***] following
                appointment of the second arbitrator, by the AAA. Such Arbitration will take place in New York, NY. The Arbitration award so given will, absent an appealable error under applicable AAA procedural rules, be a final and binding determination
                of the Claim, will be fully enforceable in any court of competent jurisdiction, and will not include any damages expressly prohibited by <u>Section 13.5</u> (Limited Liability). Ionis will pay the fees, costs, and expenses for the
                arbitrator it chooses, Metagenomi will pay the fees, costs, and expenses for the arbitrator it chooses, and the Parties will share payment of the fees, costs and expenses for the third arbitrator. Except in a proceeding to enforce the
                results of the Arbitration or as otherwise required by Applicable Law or securities exchange, neither Party nor any arbitrator may disclose the existence, content, or results of any Arbitration hereunder without the prior written consent of
                both Parties. The Parties will instruct the arbitrators to complete the Arbitration within [***] after selection of the first arbitrator by a Party and each Party will use reasonable efforts to complete such arbitration proceedings within
                such time period.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">60</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="za6728abb9478491daccef91124cbb505" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z15.1.3._Expedited_Dispute_Resolution._If"></a><a name="z_bookmark155"></a><font style="font-weight: bold;">15.1.3.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Expedited Dispute Resolution</font>. If the Executive Officers fail to reach agreement on any Expedited Dispute within [***] of submission of such Expedited Dispute to the
                Executive Officers, then either Party may notify the other Party of its intent to invoke dispute resolution under this <u>Section 15.1.3</u> (Expedited Dispute Resolution) and such Expedited Dispute will be resolved by binding arbitration
                in accordance with this <u>Section </u><u>15.1.3</u> (Expedited Dispute Resolution) except that the procedures for the conduct of such arbitration will be modified as follows:</div>
            </td>
          </tr>

      </table>
      <div style="text-align: justify; margin-right: 5.85pt; margin-left: 87pt;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z26c2bb2e05d44ae8a44d18683b16cbb5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="za_The_arbitration_will_be_conducted_by"></a>(a)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The arbitration will be conducted by a single neutral arbitrator selected by the Parties or, failing agreement by the Parties, by the AAA in accordance with the procedural rules of the AAA. Such arbitrator
                will be a retired judge or attorney with at least 20 years of relevant experience, who will be impartial and independent and will not have worked for or on behalf of either Party for at least [***]. The arbitrator will have the authority to
                engage one or more Third Party experts who are expert in the subject matter of the dispute to advise the arbitrator in rendering his or her decision (each, a &#8220;<font style="font-weight: bold;">Third Party Expert</font>&#8221;), and the costs of
                such Third Party Expert(s) will be included in the costs of the arbitration. The arbitrator will seek to obtain the mutual agreement of the Parties regarding such Third Party Expert(s), but absent such agreement, such Third Party Expert(s)
                will be selected by the arbitrator. Each Third Party Expert will be a disinterested individual who is not affiliated with either Party or its Affiliates or a Sublicensee and who has expertise and experience with respect to the subject
                matter of the Expedited Dispute, as determined by the arbitrator. Neither the Third Party Expert nor any of the Third Party Expert&#8217;s former employers will be or have been at any time an Affiliate, employee, officer or director of, or a
                consultant for, either Party or any of its Affiliates or a Sublicensee.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zef16e1e81721430998fef1b8e14f5ebf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zb_Within_15_Business_Days_of_appointme"></a>(b)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Within [***] of appointment of the arbitrator (and selection of the Third Party Expert(s)) in accordance with this <u>Section 15.1.3</u> (Expedited Dispute Resolution), the Parties will submit their written
                positions regarding the Expedited Dispute to the other Party and the arbitrator. Each Party may submit a revised written position to the arbitrator within [***] of receiving the other Party&#8217;s written position. If so requested by the
                arbitrator, each Party will make oral or other written submissions to the arbitrator in accordance with procedures to be established by the arbitrator; <font style="font-style: italic;">provided </font>that the other Party will have the
                right to be present during any oral submissions.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z174a196bafb1465a90ad5ddcebc601b3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zc_The_arbitrator_will_render_a_decisio"></a>(c)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The arbitrator will render a decision in writing within [***] (or such other time period as the Parties may agree) after receipt of the last Party&#8217;s written position, which decision will be in accordance with
                the applicable provisions of this Agreement, and such decision will be conclusive and binding on the Parties.</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">61</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="ze0ba7b121e3647ebafa6084a174afc92" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="zd_Notwithstanding_anything_to_the_cont"></a>(d)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">Notwithstanding anything to the contrary herein, the arbitration under this <u>Section </u><u>15.1.3</u> (Expedited Dispute Resolution) will be conducted as a &#8220;baseball arbitration&#8221; type proceeding. The
                arbitrator will select one of the Party&#8217;s position as his or her decision, based on what is most reasonable and equitable to each of the Parties under the circumstances and in light of the terms set forth in this Agreement, and will not
                have the authority to render any substantive decision other than to so select one Party&#8217;s position as initially submitted, or as revised in accordance with the foregoing, as applicable. The arbitrator may fashion such detailed procedures as
                the arbitrator considers appropriate to implement this intent.</div>
            </td>
          </tr>

      </table>
      <div style="margin-left: 123pt;"><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z0f2826c1b03c4d64acc904b96ae79967" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 90pt;"><br>
            </td>
            <td style="width: 36pt; vertical-align: top;"><a name="ze_The_Parties_will_instruct_the_arbitr"></a>(e)</td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">The Parties will instruct the arbitrator to complete all arbitration proceedings within [***] after selection of the arbitrator and each Party will use reasonable efforts to complete such arbitration
                proceedings within such time period.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z79f9a56dd0ad4bcda267c989a3ccbc10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z15.1.4._Tolling._The_Parties_agree_that_"></a><font style="font-weight: bold;">15.1.4.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Tolling</font>. The Parties agree that all applicable statutes of limitation and time-based defenses (such as estoppel and laches), as well as all time periods in which a
                Party must exercise rights or perform obligation hereunder, will be tolled once the dispute resolution procedures set forth in this <u>Section 15.1</u> (Dispute Resolution) have been initiated and for so long as they are pending, and the
                Parties will cooperate in taking all actions reasonably necessary to achieve such a result. In addition, during the pendency of any Claim under this Agreement initiated before the end of any applicable cure period, including under <u>Section


                  14.2.2</u> (Termination for Material Breach), (a) this Agreement will remain in full force and effect, (b) the provisions of this Agreement relating to termination for material breach with respect to such Claim will not be effective, and
                (c) neither Party will issue a notice of termination pursuant to this Agreement based on the subject matter of the arbitration, until the arbitral tribunal has confirmed the material breach and the existence of the facts claimed by a Party
                to be the basis for the asserted material breach; <font style="font-style: italic;">provided </font>that if such breach can be cured by (i) the payment of money, the defaulting Party will have an additional [***] within its receipt of the
                arbitral tribunal&#8217;s decision to pay such amount (or such later date if specified in the arbitral tribunal&#8217;s decision) or (ii) the taking of specific remedial actions, the defaulting Party will have a reasonably necessary period to
                diligently undertake and complete such remedial actions within such reasonably necessary period or any specific timeframe established by such arbitral tribunal&#8217;s decision before any such notice of termination can be issued. Further, with
                respect to any time periods that have run during the pendency of the Claim, the applicable Party will have a reasonable period of time or any specific timeframe established by such arbitral tribunal&#8217;s decision to exercise any rights or
                perform any obligations affected by the running of such time periods.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z38e6e84273db41a6aeb33978d46cb173" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.2._Designation_of_Affiliates._Each_Pa"></a><font style="font-weight: bold;">15.2.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Designation of Affiliates</font>. Each Party may discharge any obligations and exercise any rights under this Agreement through delegation of its obligations or rights to any
                of its Affiliates; <font style="font-style: italic;">provided </font>that the delegating Party will remain primarily responsible for such obligation. Each Party hereby guarantees the performance by its Affiliates of such Party&#8217;s
                obligations under this Agreement, and will cause its Affiliates to comply with the provisions of this Agreement in connection with such performance. Any breach by a Party&#8217;s Affiliate of any of such Party&#8217;s obligations under this Agreement
                will be a breach by such Party, and the other Party may proceed directly against such Party without any obligation to first proceed against such Party&#8217;s Affiliate.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze0c28966ab654da0a202a45c9c797190" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.3._Patent_Disputes._Notwithstanding_S"></a><font style="font-weight: bold;">15.3.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Patent Disputes</font>. Notwithstanding <u>Section 15.1.2</u> (Arbitration), if a dispute arises between the Parties under this Agreement with respect to the inventorship,
                interpretation, scope, validity, enforceability, applicability or term of any Patent Right, then such dispute will not be resolved pursuant to <u>Section 15.1.2</u> (Arbitration), but instead may be brought by either Party in the federal
                courts in the State of New York.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">62</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="zd5cf06e8fa6142d1b2d45c7d093a2c89" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.4._Injunctive_Relief._Notwithstanding"></a><font style="font-weight: bold;">15.4.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Injunctive Relief</font>. Notwithstanding anything to the contrary set forth in this Agreement, the Parties each stipulate and agree that (a) the other Party&#8217;s Confidential
                Information includes highly sensitive trade secret information, (b) a breach of <u>Section 3.6</u> (Exclusivity) or <u>Article 11</u> (Confidentiality), in each case, may cause irrevocable harm for which monetary damages would not provide
                a sufficient remedy, and (c) in such case of a breach of <u>Section 3.6</u> (Exclusivity) or <u>Article 11</u> (Confidentiality), the non-breaching Party will be entitled to equitable relief (including temporary or permanent restraining
                orders, specific performance or other injunctive relief) from any court of competent jurisdiction. In addition, and notwithstanding anything to the contrary set forth in this Agreement, in the event of any other actual or threatened breach
                hereunder, the aggrieved Party may seek equitable relief (including temporary or permanent restraining orders, specific performance or other injunctive relief) from any court of competent jurisdiction without first submitting to the dispute
                resolution procedures set forth in <u>Section 15.1</u> (Dispute Resolution).</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z261f16a9a9ce4aa1834e6d47b06973d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.5._Governing_Law._This_Agreement_will"></a><font style="font-weight: bold;">15.5.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Governing Law</font>. This Agreement will be governed by and construed in accordance with the laws of the State of New York without taking into consideration any choice of law
                principles that would lead to the application of the laws of another jurisdiction.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zcb67569c841d4a2daeb2691b85cc1b10" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.6._Cumulative_Remedies._The_rights_an"></a><font style="font-weight: bold;">15.6.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Cumulative Remedies</font>. The rights and remedies of the Parties under this Agreement are cumulative and not exclusive and, accordingly, are in addition to and not in lieu
                of any other rights and remedies of the Parties at law or in equity.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="ze70e1b29fd6d4e84baf89d7cf160bc6c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.7._Notices._Any_notice_or_report_requ"></a><font style="font-weight: bold;">15.7.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Notices</font>. Any notice or report required or permitted to be given or made under this Agreement by either Party to the other will be in writing and delivered to the other
                Party at its address indicated below or to such other address as the addressee will have theretofore furnished in writing to the addressor by hand, courier or by registered or certified airmail (postage prepaid), in writing, by registered
                or certified airmail (postage prepaid):</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" style="width: 100%; font-family: 'Times New Roman'; font-size: 10pt;" id="z2fe424d8993a42419cb7231c05c04e52" class="DSPFListTable">

            <tr style="vertical-align: top;">
              <td style="width: 54pt;">&#160;</td>
              <td style="vertical-align: top; width: 135pt;"><font style="font-weight: bold;"><font style="font-weight: bold;">If </font>to Ionis</font>:</td>
              <td style="vertical-align: top;">
                <div style="text-align: left;">Ionis Pharmaceuticals, Inc.</div>
              </td>
            </tr>

        </table>
      </div>
      <div style="margin-left: 189pt;">2855 Gazelle Court</div>
      <div style="margin-left: 189pt;">Carlsbad, CA 92010</div>
      <div style="margin-left: 189pt;">Attention: Chief Business Officer</div>
      <div style="margin-left: 189pt;"> <br>
      </div>
      <div style="margin-left: 54pt;">Copy to (which copy will not constitute notice):</div>
      <div style="margin-left: 189pt;">&#160;</div>
      <div style="margin-left: 189pt;">[***]</div>
      <div style="margin-left: 189pt;">Attention: General Counsel</div>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z0da291cdbe17431484512c3a165f3f82" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 135pt; vertical-align: top;"><font style="font-weight: bold;">If to Metagenomi</font>:</td>
            <td style="vertical-align: top;">
              <div>Metagenomi, Inc. </div>
              <div>1545 Park Avenue</div>
            </td>
          </tr>

      </table>
      <div style="margin-left: 189pt;">Emeryville CA 94608 <br>
        Attention: [***]</div>
      <div style="margin-left: 189pt;">&#160;</div>
      <div style="margin-left: 54pt;">Copy to (which copy will not constitute notice):</div>
      <div><br>
      </div>
      <div style="margin-left: 189pt;">Attention: [***]</div>
      <div style="margin-left: 189pt;">Copy to [***]</div>
      <div><br>
      </div>
      <div style="margin: 0px 0px 0px 51pt; text-align: justify;">All notices will be deemed effective: (a) if by courier, on the Business Day of delivery as evidenced by the courier&#8217;s receipt (or if delivered or sent on a non-Business Day, then on the
        next Business Day); or (b) if sent by registered or certified airmail, on the Business Day of receipt as evidenced on the return receipt.</div>
      <div style="text-align: justify; margin-right: 5.65pt; margin-left: 51pt;"> <br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">63</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" id="z49d21f85bdcc49d9b25de2a599f45f9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.8._Amendment_Waiver._This_Agreement_"></a><font style="font-weight: bold;">15.8.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Amendment; Waiver</font>. This Agreement (including all exhibits and attachments to this Agreement except as set forth in <u>Section 2.2.3</u> (Amendments to the Drug
                Discovery Plans) or <u>Section 2.3.2</u> (Amendments to the Exploratory Research Plan)), may be amended, modified, superseded, or cancelled only by a written agreement between the Parties, and any of the terms of this Agreement may be
                waived only by a written instrument executed by each Party or, in the case of waiver, by the Party or Parties waiving compliance. The delay or failure of either Party at any time or times to require performance of any provisions will in no
                manner affect the rights at a later time to enforce the same. No waiver by either Party of any condition or of the breach of any term contained in this Agreement, whether by conduct, or otherwise, in any one or more instances, will be
                deemed to be, or considered as, a further or continuing waiver of any such condition or of the breach of such term or any other term of this Agreement.</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <table cellspacing="0" cellpadding="0" id="z312a05543ccb45aab09ed8c8a6f7c13f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z15.9._Assignment_and_Successors._Neither"></a><a name="z_bookmark156"></a><font style="font-weight: bold;">15.9.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div style="text-align: justify;"><font style="font-weight: bold;">Assignment and Successors</font>. Neither Party may assign or transfer this Agreement in whole or in part or the licenses granted under this Agreement without the other
                Party&#8217;s prior written consent <font style="font-style: italic;">unless </font>such assignment is to (a) a Third Party successor or purchaser of all or substantially all of the assets or businesses to which this Agreement relates whether
                pursuant to a sale of assets, merger, or other transaction, in which case the assigning Party will provide prior written notice to the other Party and need not obtain the other Party&#8217;s consent or (b) an Affiliate of such Party, in which
                case the assigning Party will provide prior written notice to the other Party and need not obtain the other Party&#8217;s consent; <font style="font-style: italic;">provided </font>that, in either case, the assigning Party remains fully liable
                for the performance of its obligations hereunder by such assignee. Each Party will also have the right to sell, assign, and convey its rights to receive royalties from Net Sales of Licensed Product (with respect to Metagenomi) and
                Metagenomi Products (with respect to Ionis) and related rights to receive royalty reports and conduct audits of the other Party, its Affiliates and Sublicensees to Third Party purchasers of royalty interests. Any other assignment of this
                Agreement by a Party requires the prior written consent of the other Party. An assignment to an Affiliate will terminate, and all rights so assigned will revert to the assigning Party, if and when such Affiliate ceases to be an Affiliate of
                the assigning Party. For clarity, any assignment in violation of this <u>Section 15.9</u> (Assignment and Successors) will be null, void, and of no legal effect. This Agreement will be binding upon and inure to the benefit of the Parties
                and their respective legal representatives, successors and permitted assigns.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z74164bbf5a3e482fb1eec277a9a9750e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54.05pt; vertical-align: top;"><a name="z_TOC_250000"></a><font style="font-weight: bold;">15.10.</font></td>
            <td style="width: auto; vertical-align: top;">
              <div><font style="font-weight: bold;">Rights in Bankruptcy</font>.</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zb8e7560f94b6404e9543b4052dbf38cb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 54pt;"><br>
            </td>
            <td style="width: 36.05pt; vertical-align: top;"><a name="z15.10.1._All_rights_and_licenses_now_or_"></a><a name="z_bookmark157"></a><font style="font-weight: bold;">15.10.1.</font></td>
            <td style="vertical-align: top;">
              <div style="text-align: justify;">All rights and licenses now or hereafter granted by one Party to the other Party under or pursuant to this Agreement, including, for the avoidance of doubt, the licenses granted to Ionis pursuant to <u>Section


                  3.1</u> (License Grant to Ionis), are, for all purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to &#8220;intellectual property&#8221; as defined in the U.S. Bankruptcy Code. Upon the occurrence of any Insolvency Event with
                respect to a Party granting a license (the &#8220;<font style="font-weight: bold;">Licensing Party</font>&#8221;), the Licensing Party agrees that the other Party (the &#8220;<font style="font-weight: bold;">Licensee</font>&#8221;), as licensee of such rights
                under this Agreement, will retain and may fully exercise all of its rights and elections under the U.S. Bankruptcy Code. Without limiting the generality of the foregoing, the Parties intend and agree that any sale of a Licensing Party&#8217;s
                assets under Section 363 of the U.S. Bankruptcy Code will be subject to Ionis&#8217; rights under Section 365(n), that the Licensee cannot be compelled to accept a money satisfaction of its interests in the intellectual property licensed pursuant
                to this Agreement, and that any such sale therefore may not be made to a purchaser &#8220;free and clear&#8221; of the Licensee&#8217;s rights under this Agreement and Section 365(n) without the express, contemporaneous consent of the Licensee. The Licensing
                Party will, during the Term, create and maintain current copies or, if not amenable to copying, detailed descriptions or other appropriate embodiments, to the extent feasible, of all intellectual property licensed under this Agreement. Each
                Party acknowledges and agrees that &#8220;embodiments&#8221; of intellectual property within the meaning of Section 365(n) include laboratory notes and notebooks, cell lines, laboratory samples, product samples and inventory, research studies and data,
                all Regulatory Approvals (and all applications for Regulatory Approval) and rights of reference therein, marketing advertising and promotional materials, the Licensed Technology, and all information related to the Licensed Technology. If
                (a) a case under the U.S. Bankruptcy Code is commenced by or against a Licensing Party, (b) this Agreement is rejected as provided in the U.S. Bankruptcy Code, and (c) the Licensee elects to retain its rights hereunder as provided in
                Section 365(n) of the U.S. Bankruptcy Code, the Licensing Party (in any capacity, including debtor-in-possession) and its successors and assigns (including a trustee) will:</div>
            </td>
          </tr>

      </table>
      <div> <br>
      </div>
      <div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">64</font></div>
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="z784d63a69df74a38b57dc4ea00df780e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="za_provide_the_Licensee_with_all_such_i"></a>(a)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">provide the Licensee with all such intellectual property (including all embodiments thereof) held by the Licensing Party and such successors and assigns, or otherwise available to them, immediately upon
                  Ionis&#8217; written request. Whenever the Licensee or any of its successors or assigns provides to Ionis any of the intellectual property licensed hereunder (or any embodiment thereof) pursuant to this <u>Section 15.10.1</u>, the Licensee
                  will have the right to perform the Licensing Party&#8217;s obligations hereunder with respect to such intellectual property, but neither such provision nor such performance by the Licensee will release the Licensing Party from liability
                  resulting from rejection of the license or the failure to perform such obligations; and</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zed9cac83599d4626a62d04cfdaa7c040" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zb_not_interfere_with_the_Licensees_ri"></a>(b)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">not interfere with the Licensee&#8217;s rights under this Agreement, or any agreement supplemental hereto, to such intellectual property (including such embodiments), including any right to obtain such
                  intellectual property (or such embodiments) from another entity, to the extent provided in Section 365(n) of the U.S. Bankruptcy Code.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z92813c7eae294d3c90a3c2f5ade903c2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54pt;"><br>
              </td>
              <td style="width: 36.05pt; vertical-align: top;"><a name="z15.10.2._All_rights_powers_and_remedies"></a><font style="font-weight: bold;">15.10.2.</font></td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">All rights, powers and remedies of the Licensee provided herein are in addition to and not in substitution for any other rights, powers, and remedies now or hereafter existing at law or in equity (including
                  the U.S. Bankruptcy Code) in the event of the commencement of a case under the U.S. Bankruptcy Code with respect to the Licensing Party. The Parties intend the following rights to extend to the maximum extent permitted by Applicable Law,
                  and to be enforceable under U.S. Bankruptcy Code Section 365(n):</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z05b0577c0e4a43608008fcfaf33d9398" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="za_the_right_of_access_to_any_intellect"></a>(a)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">the right of access to any intellectual property rights (including all embodiments thereof) of the Licensing Party, or any Third Party with whom the Licensing Party contracts to perform an obligation of the
                  Licensing Party under this Agreement, and, in the case of any such Third Party, which is necessary for the Manufacture, use, sale, import, or export of Licensed Systems and Licensed Products; and</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z5601b62e064943ad83189761daae9b33" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zb_the_right_to_contract_directly_with_"></a>(b)</td>
              <td style="vertical-align: top;">
                <div>the right to contract directly with any Third Party to complete the contracted work.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7ca6443c758f4f59888f9aa75408811f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.11._Force_Majeure._Neither_Party_will"></a><font style="font-weight: bold;">15.11.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Force Majeure</font>. Neither Party will be held liable or responsible to the other Party nor be deemed to be in default under, or in breach of any provision of, this
                  Agreement for failure or delay in fulfilling or performing any obligation (other than a payment obligation) of this Agreement to the extent such failure or delay is due to force majeure. For purposes of this Agreement, &#8220;<font style="font-weight: bold;">Force Majeure</font>&#8221; is defined as any cause beyond the reasonable control of the affected Party and without the fault or negligence of such Party, which may include acts of God; material changes in
                  Applicable Law; war; civil commotion; destruction of production facilities or materials by fire, flood, earthquake, explosion or storm; labor disturbances; epidemic; pandemic; quarantine; and failure of public utilities or common
                  carriers. The Parties agree the effects of the COVID-19 pandemic that is ongoing as of the Effective Date (including related government orders) may be invoked as a Force Majeure for the purposes of this Agreement, even though the pandemic
                  is ongoing, only to the extent those effects are not reasonably foreseeable by the Parties as of the Effective Date. Notwithstanding the foregoing, a Party will not be excused from making payments owed hereunder due to any Force Majeure
                  circumstances affecting such Party. In the case of a Force Majeure, the Party affected by such Force Majeure will immediately notify the other Party of such inability and of the period for which such inability is expected to continue. The
                  Party giving such notice will thereupon be excused from such of its obligations under this Agreement as it is thereby disabled from performing for so long as it is so disabled for up to a maximum of [***], after which time the Parties
                  will promptly meet to discuss in good faith how to best proceed in a manner that maintains and abides by the Agreement. To the extent possible, the Party affected by such Force Majeure will use reasonable efforts to minimize the duration
                  of any Force Majeure.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">65</font></div>
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="zd498489f9b154bc293feab38c254b7b4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.12._Interpretation._The_Parties_ackno"></a><font style="font-weight: bold;">15.12.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Interpretation</font>. The Parties acknowledge and agree that: (a) each Party and its counsel reviewed and negotiated the terms and provisions of this Agreement and have
                  contributed to its revision; (b) the rule of construction to the effect that any ambiguities are resolved against the drafting Party will not be employed in the interpretation of this Agreement; and (c) the terms and provisions of this
                  Agreement will be construed fairly as to each Party and not in a favor of or against either Party, regardless of which Party was generally responsible for the preparation of this Agreement. In addition, except as otherwise explicitly
                  specified to the contrary, (i) references to a section, schedule or exhibit means a section of, or schedule or exhibit to this Agreement, unless another agreement is specified, (ii) the word &#8220;including&#8221; (in its various forms) means
                  &#8220;including without limitation,&#8221; (iii) the words &#8220;shall&#8221; and &#8220;will&#8221; have the same meaning, (iv) references to a particular statute or regulation include all rules and regulations thereunder and any predecessor or successor statute, rules
                  or regulations, in each case as amended or otherwise modified from time-to-time, (v) words in the singular will be held to include the plural and vice versa, and words of one gender will be held to include all genders as the context
                  requires, (vi) references to a particular Person include such Person&#8217;s successors and assigns to the extent not prohibited by this Agreement, (vii) references to &#8220;days&#8221; will mean calendar days, unless otherwise specified, (viii) the word
                  &#8220;or&#8221; will not be exclusive, unless the context otherwise requires, (ix) the titles and headings contained in this Agreement are for reference purposes only and will not affect in any way the meaning or interpretation of this Agreement,
                  (x) the terms &#8220;hereof,&#8221; &#8220;hereby,&#8221; &#8220;hereto,&#8221; and derivative or similar words refer to this entire Agreement, including any schedules or exhibits hereto, and (xi) unless otherwise specified, &#8220;$&#8221; is in reference to United States Dollars.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb230937e3a604e61a0a4fdb243308a36" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.13._Integration._This_Agreement_toge"></a><font style="font-weight: bold;">15.13.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Integration</font>. This Agreement, together with all exhibits and schedules attached hereto and each Co-Development and Co-Commercialization Agreement, any Development
                  Supply Agreement, and any Commercial Supply Agreement, sets forth the entire agreement with respect to the subject matter hereof and thereof and supersedes all other agreements and understandings between the Parties with respect to such
                  subject matter, including the Confidentiality Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z3a52b07940e34df2a66cae7f08a7f187" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.14._Severability._Each_Party_hereby_a"></a><font style="font-weight: bold;">15.14.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Severability</font>. Each Party hereby agrees that it does not intend to violate any public policy, statutory or common laws, rules, regulations, treaty, or decision of any
                  government agency or executive body thereof of any country or community or association of countries. If one or more provisions of this Agreement be or become invalid, then the Parties will substitute, by written agreement, valid
                  provisions for such invalid provisions, which valid provisions in their economic effect are sufficiently similar to the invalid provisions such that it can be reasonably assumed that the Parties would have entered into this Agreement with
                  such valid provisions. If the Parties are unable to agree upon such alternative valid provision, then the invalidity of one or several provisions of this Agreement will not affect the validity of this Agreement as a whole, unless the
                  invalid provisions are of such essential importance to this Agreement such that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid provisions.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">66</font></div>
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="zefa909eb444042ea866720dcf2588b42" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.15._Further_Assurances._Each_of_Ionis"></a><font style="font-weight: bold;">15.15.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Further Assurances</font>. Each of Ionis and Metagenomi agrees to duly execute and deliver, or cause to be duly executed and delivered, such further instruments and do and
                  cause to be done such further acts and things, including, the filing of such additional assignments, agreements, documents and instruments, as the other Party may at any time and from time-to-time reasonably request in connection with
                  this Agreement or to carry out more effectively the provisions and purposes of, or to better assure and confirm unto such other Party its rights and remedies under, this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z8c8b66604e044b42b9e888ba0ef85fd4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.16._Counterparts._This_Agreement_may_"></a><font style="font-weight: bold;">15.16.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Counterparts</font>. This Agreement may be executed in counterparts, all of which taken together will be regarded as one and the same instrument. Counterparts may be
                  delivered via electronic mail, including Adobe&#8482; Portable Document Format (PDF) or any electronic signature complying with the U.S. Federal ESIGN Act of 2000, and any counterpart so delivered will be deemed to be original signatures, will
                  be valid and binding upon the Parties, and, upon delivery, will constitute due execution of this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z75f5206caf5f48a1a428854697bd2453" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z15.17._Relationship_of_the_Parties._In_e"></a><a name="z_bookmark158"></a><font style="font-weight: bold;">15.17.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;"><font style="font-weight: bold;">Relationship of the Parties</font>. In entering into this Agreement and performing their respective duties and obligations with respect to the Agreement, the Parties are
                  acting, and intend to be treated, as independent entities, and the activities and resources of each Party will be managed by such Party, acting independently and in its individual capacity. The relationship between the Parties is that of
                  independent contractors, and neither Party will have the power to bind or obligate the other Party in any manner. Nothing contained in this Agreement will be construed or implied to create an agency, partnership, joint venture, fiduciary,
                  or employer-employee relationship between the Parties. Except as otherwise expressly provided in this Agreement, neither Party may make any representation, warranty or commitment, whether express or implied, on behalf of or incur any
                  charges or expenses for or in the name of the other Party. Neither Party will hold itself out, or take any action, contrary to the terms of this <u>Section 15.17</u> (Relationship of the Parties), and neither Party will become liable due
                  to any such representation, warranty, commitment, act or omission made by the other Party contrary to the provisions of this <u>Section 15.17</u> (Relationship of the Parties). Subject to the terms of this Agreement, the activities and
                  resources of each Party will be managed by such Party, acting independently and in its individual capacity.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <div style="text-align: center; margin-right: 114.15pt; margin-left: 123.2pt; font-style: italic;">[Remainder of page intentionally left blank.]</div>
        <div><br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">67</font></div>
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-indent: 36pt; margin-left: 14.95pt;"><a name="Ionis_Sig_Page.pdf"></a>IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed by their duly authorized representatives.</div>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" border="0" id="z364b6fb6aec64aafb5aa6eb818a0b1bc" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);">

            <tr>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold;" rowspan="1" colspan="2">METAGENOMI, INC.</td>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold; width: 5%;" rowspan="1" colspan="1">&#160;</td>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold;" rowspan="1" colspan="2">IONIS PHARMACEUTICALS, INC.</td>
            </tr>
            <tr>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold;" rowspan="1" colspan="2">&#160;</td>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold; width: 5%;" rowspan="1" colspan="1">&#160;</td>
              <td style="vertical-align: top; padding-bottom: 2px; font-weight: bold;" rowspan="1" colspan="2">&#160;</td>
            </tr>
            <tr>
              <td style="width: 3%; vertical-align: top; padding-bottom: 2px;" rowspan="1">&#160;By:</td>
              <td style="width: 44%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><font style="font-style: italic;">/s/ Brian Thomas</font></td>
              <td style="width: 5%; vertical-align: top; padding-bottom: 2px;" rowspan="1" colspan="1">&#160;</td>
              <td style="width: 3%; vertical-align: top; padding-bottom: 2px;" rowspan="1">By:</td>
              <td style="width: 45%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);" rowspan="1"><font style="font-style: italic;">/s/ Brett Monia</font></td>
            </tr>
            <tr>
              <td style="width: 3%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 44%; vertical-align: top;" rowspan="1">Name: Brian Thomas</td>
              <td style="width: 5%; vertical-align: top;" rowspan="1" colspan="1">&#160;</td>
              <td style="width: 3%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 45%; vertical-align: top;" rowspan="1">Name: Brett Monia</td>
            </tr>
            <tr>
              <td style="width: 3%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 44%; vertical-align: top;" rowspan="1">Title: Chief Executive Officer</td>
              <td style="width: 5%; vertical-align: top;" rowspan="1" colspan="1">&#160;</td>
              <td style="width: 3%; vertical-align: top;" rowspan="1">&#160;</td>
              <td style="width: 45%; vertical-align: top;" rowspan="1">Title: Chief Executive Officer</td>
            </tr>

        </table>
        <div><br>
        </div>
        <div style="text-align: center; margin-left: 1pt;">[<font style="font-style: italic;">Signature Page to Collaboration and License Agreement</font>]</div>
        <div><br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-align: center; font-weight: bold;"><u>Appendix 1</u></div>
        <div>&#160;</div>
        <div style="text-align: center; font-weight: bold;">Definitions</div>
        <div><br>
        </div>
        <div style="margin-left: 90pt; text-align: justify;"><a name="For_purposes_of_this_Agreement_whether_"></a>For purposes of this Agreement, whether used in the singular or plural, the following terms will have the meanings set forth below:</div>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z550bf83ad218424784bb33a001574093" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.1._AAA_has_the_meaning_set_forth_in_"></a><font style="font-weight: bold;">1.1.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">AAA</font>&#8221; has the meaning set forth in <u>Section 15.1.2</u> (Arbitration).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z867878037b584e3c90ed081b74dd9dd5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.2._Accounting_Standards_means_United"></a><font style="font-weight: bold;">1.2.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Accounting Standards</font>&#8221; means United States Generally Accepted Accounting Principles, as generally and consistently applied throughout a Party&#8217;s organization.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="ze03f39155dbc493db8a270271358b6b4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.3._Acquiring_Party_has_the_meaning_s"></a><font style="font-weight: bold;">1.3.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Acquiring Party</font>&#8221; has the meaning set forth in <u>Section 9.8.1</u> (Proposed New In-License Agreement).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zd2f22dc78d934a7ba04e2d35f6c272dc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.4._Acquisition_Transaction_has_the_m"></a><font style="font-weight: bold;">1.4.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Acquisition Transaction</font>&#8221; has the meaning set forth in <u>Section 3.6.2</u> (Acquisition of Distracting Product).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z677942271a8546abbc54c36411806cf1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.5._Additional_Drug_Discovery_Plan_ha"></a><font style="font-weight: bold;">1.5.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Additional Drug Discovery Plan</font>&#8221; has the meaning set forth in <u>Section 2.2.2</u> (Additional Drug Discovery Plans).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z159c666bf4974df98b8ad0024fdd3e91" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.6._Additional_Wave_1_Target_has_the_"></a><font style="font-weight: bold;">1.6.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Additional Wave 1 Target</font>&#8221; has the meaning set forth in <u>Section 2.1.1(c)</u> (Additional Wave 1 Target Selection).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7f8bfce4d63d40fb9630e5befb58b3d1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.7._Additional_Wave_1_Target_Notice_h"></a><font style="font-weight: bold;">1.7.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Additional Wave 1 Target Notice</font>&#8221; has the meaning set forth in <u>Section 2.1.1(c)</u> (Additional Wave 1 Target Selection).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z67e4f1b6a8e64e9e8be85c44bb93a6fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.8._Additional_Wave_1_Target_Selection"></a><font style="font-weight: bold;">1.8.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Additional Wave 1 Target Selection Period</font>&#8221; has the meaning set forth in <u>Section 2.1.1(c)</u> (Additional Wave 1 Target Selection).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zb51346b48c3e4db59dcab2f32eda4c6a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.9._Affiliate_means_as_of_any_point_"></a><a name="z_bookmark159"></a><font style="font-weight: bold;">1.9.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Affiliate</font>&#8221; means, as of any point in time and for so long as such relationship continues to exist with respect to any Person, any other Person that controls, is
                  controlled by, or is under common control with such Person. For purposes of this <u>Section 1.9</u> (Affiliate), the term &#8220;control&#8221; (including, with correlative meaning, the terms &#8220;controlled by&#8221; and &#8220;under common control with&#8221;), means
                  the possession, directly or indirectly, of more than 50% of the voting stock or other ownership interest of such Person, or the possession, directly or indirectly, of the power to direct or cause the direction of the affairs or management
                  and policies of such Person or the power to elect or appoint more than 50% of the members of the governing body of such Person. The Parties acknowledge that in the case of certain entities organized under the laws of certain countries
                  outside the United States, the maximum percentage ownership permitted by Applicable Law for a foreign investor may be less than 50%, and that in such case such lower percentage will be substituted in the preceding sentence; <font style="font-style: italic;">provided </font>that such foreign investor has the power to direct the management and policies of such entity.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z48b8422a23b044ad98aede0fd0be7849" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.10._Agreement_has_the_meaning_set_fo"></a><font style="font-weight: bold;">1.10.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Agreement</font>&#8221; has the meaning set forth in the Preamble.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zfa033e2e699d41c99d715e1c70c8fcaf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.11._Alliance_Manager_has_the_meaning"></a><font style="font-weight: bold;">1.11.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Alliance Manager</font>&#8221; has the meaning set forth in <u>Section 4.4</u> (Alliance Managers).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z5d46d1345c3144c28c31ed45ae310a1a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.12._Allowable_Overruns_means_any_amo"></a><font style="font-weight: bold;">1.12.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means any amount that is less than [***], on a year to date basis, set forth in the Exploratory Research Budget or a Drug Discovery Budget (as applicable) for
                  such Calendar Year; <font style="font-style: italic;">provided </font>that such amount is not incurred as a result of any breach by Metagenomi of this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z2e6d0075df464c5eb2ba457034859c13" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.13._Annual_Net_Sales_means_with_res"></a><font style="font-weight: bold;">1.13.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Annual Net Sales</font>&#8221; means, with respect to an Ionis Product, the aggregate Net Sales of such Ionis Product sold by Ionis, its Affiliates, or Sublicensees in the Field
                  in the Territory during a Calendar Year and only during the Royalty Term for such Ionis Product in the applicable country.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="zc31e34c9a41c4314b91539434df4ced9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.14._Applicable_Law_means_applicable_"></a><font style="font-weight: bold;">1.14.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Applicable Law</font>&#8221; means applicable (with respect to the particular activity, task, or obligation under this Agreement to which such term applies) laws, statutes,
                  rules, regulations, and other pronouncements having the effect of law of any Governmental Authority that may be in effect from time to time, including for clarity any applicable rules, regulations, guidelines, or other requirements of any
                  Regulatory Authority that may be in effect from time to time.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zccee7b5d8a7547639ae9ea2c67a57491" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.15._Arbitration_has_the_meaning_set_"></a><font style="font-weight: bold;">1.15.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Arbitration</font>&#8221; has the meaning set forth in <u>Section 15.1.2</u> (Arbitration).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.16._Audited_Party_has_the_meaning_se"></a><font style="font-weight: bold;">1.16.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Audited Party</font>&#8221; has the meaning set forth in <u>Section 9.13.1</u> (Books and Records).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.17._Auditing_Party_has_the_meaning_s"></a><font style="font-weight: bold;">1.17.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Auditing Party</font>&#8221; has the meaning set forth in <u>Section 9.13.1</u> (Books and Records).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.18._Auditor_has_the_meaning_set_fort"></a><font style="font-weight: bold;">1.18.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Auditor</font>&#8221; has the meaning set forth in <u>Section 9.13.1</u> (Books and Records).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.19._Available_means_with_respect_to"></a><font style="font-weight: bold;">1.19.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Available</font>&#8221; means, with respect to a Proposed Target, that such Proposed Target is not an Encumbered Target.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.20._Available_Gene_Editing_Modality_"></a><font style="font-weight: bold;">1.20.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.2.4(a)</u> (New [***]).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z2dd1a53ebef7447aa3c8f85bcd77d8fb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.21._Biosimilar_Product_means_with_r"></a><font style="font-weight: bold;">1.21.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Biosimilar Product</font>&#8221; means, with respect to a particular Licensed Product in a particular country, a product on the market in such country commercialized by any Third
                  Party that is not a Sublicensee and that did not purchase such product in a chain of distribution that included any of Ionis or its Affiliates or Sublicensees, that (a) is approved by the applicable Regulatory Authority, under any
                  then-existing laws and regulations in the applicable country pertaining to approval of generic or biosimilar biologic products, as a &#8220;generic&#8221; or &#8220;biosimilar&#8221; version of such Licensed Product, which approval uses such Licensed Product as
                  a reference product and relies on or references information in the MAA for such Licensed Product, or (b) is otherwise recognized by the applicable Regulatory Authority as a biosimilar or interchangeable product to such Licensed Product.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z2f35d8edef404a8198a1d13ebb23582d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.22._BLA_means_a_biologics_license_ap"></a><font style="font-weight: bold;">1.22.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">BLA</font>&#8221; means a biologics license application that is submitted to the FDA for a Licensed Product, pursuant to 21 C.F.R. &#167; 601.2.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.23._Business_Day_means_any_day_othe"></a><font style="font-weight: bold;">1.23.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Business Day</font>&#8221; means any day, other than Saturday, Sunday, or any day on which banking institutions in California are authorized or required by Applicable Law to
                  remain closed.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.24._C.F.R._means_the_U.S._Code_of_Fe"></a><font style="font-weight: bold;">1.24.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">C.F.R.</font>&#8221; means the U.S. Code of Federal Regulations.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.25._Calendar_Quarter_means_each_peri"></a><font style="font-weight: bold;">1.25.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Calendar Quarter</font>&#8221; means each period of three consecutive calendar months ending on March 31, June 30, September 30, or December 31, except that the first Calendar
                  Quarter of the Term will commence on the Effective Date, and the last Calendar Quarter of the Term will end on the effective date of the termination or expiration of this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb0e9075549af4555acd82a91aff9a839" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.26._Calendar_Year_means_each_period_"></a><font style="font-weight: bold;">1.26.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Calendar Year</font>&#8221; means each period of 12 consecutive calendar months commencing on January 1 and ending on December 31, except that the first Calendar Year of the Term
                  will commence on the Effective Date, and the last Calendar Year of the Term will end on the effective date of the termination or expiration of this Agreement.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.27._Change_of_Control_means_with_re"></a><font style="font-weight: bold;">1.27.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Change of Control</font>&#8221; means, with respect to a Party, (a) a merger, reorganization, combination, or consolidation of such Party with a Third Party that results in the
                  holders of beneficial ownership of the voting securities or other voting interests of such Party (or, if applicable, the ultimate parent of such Party) immediately prior to such merger, reorganization, combination, or consolidation
                  ceasing to hold beneficial ownership of more than 50% of the combined voting power of the surviving entity or the ultimate parent of the surviving entity immediately after such merger, reorganization, combination or consolidation, (b) a
                  transaction or series of related transactions in which a Third Party, together with its Affiliates, becomes the beneficial owner of 50% or more of the combined voting power of the outstanding securities or other voting interest of such
                  Party, (c) the sale, lease, exchange, contribution, or other transfer (in one transaction or a series of related transactions) to a Third Party of all or substantially all of such Party&#8217;s assets, or (d) a liquidation or dissolution of
                  such Party or any direct or indirect parent of such Party. Notwithstanding the foregoing, an initial public offering, a <font style="font-style: italic;">bona fide </font>venture capital financing, a SPAC transaction, or reverse-merger
                  transaction, in each case, of Metagenomi, will not be considered a Change of Control of Metagenomi.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7de603b87b124c40b75ed574bd606c01" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.28._Claim_has_the_meaning_set_forth_"></a><font style="font-weight: bold;">1.28.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Claim</font>&#8221; has the meaning set forth in <u>Section 15.1.1</u> (Escalation).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z232671217d95453a9564deff56db1b35" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.29._Clinical_Trial_means_any_clinica"></a><font style="font-weight: bold;">1.29.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Clinical Trial</font>&#8221; means any clinical trial in humans that is designed to generate data in support or maintenance of an IND or MAA.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.30._CMO_means_a_contract_manufacturi"></a><font style="font-weight: bold;">1.30.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">CMO</font>&#8221; means a contract manufacturing organization.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.31._CNS_means_the_brain_spinal_cord"></a><font style="font-weight: bold;">1.31.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means [***].</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="ze2ae4276d3934ee0ae50f4b72f7f79e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.32._Co-Co_Option_has_the_meaning_set"></a><font style="font-weight: bold;">1.32.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Co Option</font>&#8221; has the meaning set forth in <u>Section 5.1.1</u> (Option Grant).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.33._Co-Co_Option_Notice_has_the_mean"></a><font style="font-weight: bold;">1.33.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Co Option Notice</font>&#8221; has the meaning set forth in <u>Section 5.1.2</u> (Option Period).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z0d15146403984ec099bd457960b3f9e7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.34._Co-Co_Option_Period_has_the_mean"></a><font style="font-weight: bold;">1.34.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Co Option Period</font>&#8221; has the meaning set forth in <u>Section 5.1.2</u> (Option Period).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb9e2810dbf23438896e3600f655913e8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.35._Co-Co_Products_means_any_License"></a><font style="font-weight: bold;">1.35.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Co Products</font>&#8221; means any Licensed Products that are the subject of a Co-Co Program.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.36._Co-Co_Program_means_each_Drug_Di"></a><font style="font-weight: bold;">1.36.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Co Program</font>&#8221; means each Drug Discovery Program for which Metagenomi exercises a Co- Co Option in accordance with <u>Section 5.1</u> (Co-Development and
                  Co-Commercialization Options).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze1df8a8581334913bda69f2963cae896" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.37._Co-Development_and_Co-Commerciali"></a><font style="font-weight: bold;">1.37.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Co-Development and Co-Commercialization Agreement</font>&#8221; has the meaning set forth in <u>Section</u><u> 5.2</u> (Development and Commercialization of the Co-Co Products;
                  Opt-Down Right).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z3701588d9cf94882a8eed9034476f6ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.38._Collaboration_Activities_has_the"></a><font style="font-weight: bold;">1.38.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Activities</font>&#8221; has the meaning set forth in <u>Section 2.4</u> (Conduct of Collaboration Activities).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc18a2423f0e14daebc3e9d5a64eab7a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.39._Collaboration_Program_means_a_"></a><font style="font-weight: bold;">1.39.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Program</font>&#8221; means (a) the Exploratory Research Program and (b) each Drug Discovery Program.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zd726ef0306934b3092bf5a1a468113a5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.40._Collaboration_Program_Plans_has_"></a><font style="font-weight: bold;">1.40.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Program Plans</font>&#8221; has the meaning set forth in <u>Section 2.4</u> (Conduct of Collaboration Activities).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc7a5e5d8462b43a69867e0f504210ab3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.41._Collaboration_Program_Report_has"></a><font style="font-weight: bold;">1.41.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Program Report</font>&#8221; has the meaning set forth in <u>Section 2.6.2</u> (Collaboration Program Reports).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zd6e519592ee1424aa6452b7cb1a5f99c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.42._Collaboration_Target_means_as_a"></a><font style="font-weight: bold;">1.42.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Target</font>&#8221; means, as applicable, any of (a) [***], (b) the Second Wave 1 Target, and (c) the Proposed Targets that Ionis designates in accordance with <u>Section


                    2.1.4(c)</u> (Effects if a Proposed Target is Available).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zcb45bf2dcde844bf9c37466bc0154ee4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.43._Collaboration_Term_means_a_wit"></a><font style="font-weight: bold;">1.43.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Collaboration Term</font>&#8221; means (a) with respect to a Drug Discovery Program, the applicable Drug Discovery Term for such Drug Discovery Program and (b) with respect to
                  the Exploratory Research Program, the Exploratory Research Term.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.44._Combination_Product_has_the_mean"></a><font style="font-weight: bold;">1.44.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Combination Product</font>&#8221; has the meaning set forth in <u>Section 1.190</u> (Net Sales).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.45._Commercial_Supply_Agreement_has_"></a><font style="font-weight: bold;">1.45.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Commercial Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Metagenomi Supply Term).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z92928fa25d5d49d88e2927c4fd73c1f1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.46._Commercialization_or_Commercial"></a><font style="font-weight: bold;">1.46.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Commercialization</font>&#8221; or &#8220;<font style="font-weight: bold;">Commercialize</font>&#8221; means with respect to any product, any and all activities directed to the marketing,
                  promotion, patient services, distribution, pricing, reimbursement, pharmacovigilance, import, export, offering for sale, and sale of such product, including seeking and maintaining any required Pricing Approval, but excluding any
                  activities directed to Manufacturing, Development, or Medical Affairs. &#8220;<font style="font-weight: bold;">Commercialize</font>,&#8221; &#8220;<font style="font-weight: bold;">Commercializing</font>,&#8221; and &#8220;<font style="font-weight: bold;">Commercialized</font>&#8221;
                  will be construed accordingly.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb432e1aaa10b4b5688b1c515b74de9c7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.47._Commercially_Reasonable_Efforts_"></a><font style="font-weight: bold;">1.47.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Commercially Reasonable Efforts</font>&#8221; means with respect to the efforts to be expended by any Person with respect to any objective, reasonable, diligent, and good faith
                  efforts to accomplish such objective. With respect to Ionis&#8217; obligations set forth in <u>Section 6.1.3</u> (Development Diligence for the Ionis Products) and <u>Section 6.2.2</u> (Commercialization Diligence for the Ionis Products), &#8220;<font style="font-weight: bold;">Commercially Reasonable Efforts</font>&#8221; means that level, caliber, and quality of efforts and resources reasonably and normally used by biopharmaceutical companies of similar size to Ionis as to a potential or
                  actual product with similar commercial potential and at a similar stage of product life, taking into account with respect to each applicable Licensed System or Licensed Product, (a) issues of safety, efficacy, and product profile, (b)
                  likelihood of receiving Regulatory Approval (including, for clarity, Pricing Approval) of the applicable Licensed Product, (c) regulatory structure involved, (d) feedback provided by any Regulatory Authority, including relating to
                  proposed or approved labeling, (e) competitiveness in the marketplace and anticipated or actual profitability of the product (including based on the Pricing Approval and the cost of goods thereof, where applicable), (f) proprietary
                  position, and (g) other scientific, technical, and business factors deemed relevant by Ionis. &#8220;<font style="font-weight: bold;">Commercially Reasonable Efforts</font>&#8221; will be determined on a country-by-country basis in the relevant
                  countries and [***].</div>
              </td>
            </tr>

        </table>
        <br>
        <table cellspacing="0" cellpadding="0" id="ze4814b16447b427692de3a6aa85541de" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.48._Common_Ownership_Legislation_mea"></a><font style="font-weight: bold;">1.48.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Common Ownership Legislation</font>&#8221; means the legislation on conditions for patentability and novelty, as codified at 35 U.S.C. &#167; 102(c) (Common Ownership Under Joint
                  Research Agreements).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zabce5a4ba13c4ad7947bafc7fe0bcf9c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.49._Competitive_Infringement_has_the"></a><font style="font-weight: bold;">1.49.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Competitive Infringement</font>&#8221; has the meaning set forth in <u>Section 10.3.1</u> (Notification).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze7da00d0b3894e5cb89825153aad30b7" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.50._Confidential_Information_means_"></a><font style="font-weight: bold;">1.50.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Confidential Information</font>&#8221; means (a) the existence and terms of this Agreement, and (b) with respect to each Party, Know-How, materials, and other proprietary
                  information including data and all other scientific, pre-clinical, clinical, regulatory, Manufacturing, marketing, financial, and commercial information or data that is disclosed, made available to, or provided by or on behalf of such
                  Party to the other Party or to any of the Receiving Party&#8217;s employees, consultants, Affiliates, or Sublicensees, whether or not specifically marked or designated by the Disclosing Party as confidential; <font style="font-style: italic;">provided


                  </font>that, notwithstanding the foregoing, Product-Specific Know-How will be deemed the Confidential Information of Ionis during the Term and thereafter following any expiration, but not termination, of this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z840a42285354463e830bd90dc1db4ba5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.51._Confidentiality_Agreement_has_th"></a><font style="font-weight: bold;">1.51.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Confidentiality Agreement</font>&#8221; has the meaning set forth in <u>Section 11.1.2</u> (Confidential Information of Each Party).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="zd689916ff2934beaa188fdff9ebfa91d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.52._Control_or_Controlled_means_th"></a><font style="font-weight: bold;">1.52.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Control</font>&#8221; or &#8220;<font style="font-weight: bold;">Controlled</font>&#8221; means the possession by a Party (whether by ownership, license, or otherwise other than pursuant to
                  this Agreement) of, (a) with respect to any materials or other tangible Know-How, the legal authority or right to physical possession of such materials or tangible Know-How, with the right to provide such materials or tangible Know-How to
                  the other Party on the terms set forth herein, (b) with respect to Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual property, the legal authority or right to grant a license,
                  sublicense, access, or right to use (as applicable) to the other Party under such Patent Rights, Regulatory Approvals, Regulatory Submissions, intangible Know-How, or other intellectual property on the terms set forth herein, in each case
                  ((a) and (b)), without breaching or otherwise violating the terms of any arrangement or agreement with a Third Party in existence as of the time such Party or its Affiliates would first be required hereunder to grant the other Party such
                  access, right to use, license, or sublicense, and (c) with respect to any product, the legal authority or right to grant an exclusive license or sublicense under Patent Rights that Cover such product or Know-How that relates to such
                  product; <font style="font-style: italic;">provided </font>that (i) any Know-How or Patent Rights in-licensed or acquired by Metagenomi or its Affiliates under an Existing Potential Metagenomi In-License Agreement or a Proposed New
                  Metagenomi In-License Agreement will not be deemed &#8220;Controlled&#8221; by Metagenomi unless and until such agreement becomes a Metagenomi In-License Agreement under <u>Section 9.7.1</u> (Effective Date Licensed Technology; Existing Metagenomi
                  In-License Agreements) or <u>Section 9.8.2</u> (Acceptance of a Proposed New In- License Agreement) (and only for so long as it remains a New Metagenomi In-License Agreement hereunder) and (ii) any Know-How or Patent Rights in-licensed
                  or acquired by Ionis or its Affiliates under an Existing Potential Ionis In-License Agreement or a Proposed New Ionis In-License Agreement will not be deemed &#8220;Controlled&#8221; by Ionis unless and until such agreement becomes an Ionis
                  In-License Agreement under <u>Section 9.7.2</u> (Existing Potential Ionis In-License Agreements) or <u>Section 9.8.2</u> (Acceptance of a Proposed New In-License Agreement) (and only for so long as it remains an Ionis In-License
                  Agreement hereunder). Notwithstanding the foregoing, a Party and its Affiliates will not be deemed to &#8220;<font style="font-weight: bold;">Control</font>&#8221; any of the foregoing (a) &#8211; (c) that are owned or controlled by a Third Party described
                  in the definition of &#8220;Change of Control,&#8221; or such Third Party&#8217;s Affiliates (other than an Affiliate of such Party prior to the Change of Control), (x) prior to the closing of such Change of Control, except to the extent that any such
                  Patent Rights or Know-How were developed by such Third Party prior to such Change of Control using or incorporating such Party&#8217;s or its pre-existing Affiliate&#8217;s Know-How or Patent Rights, or (y) after such Change of Control to the extent
                  that such Patent Rights or Know-How are developed or conceived by such Third Party or its Affiliates (other than such Party) after such Change of Control without using or incorporating such Party&#8217;s or its pre-existing Affiliate&#8217;s Know-How
                  or Patent Rights and are not developed or conceived by personnel who were employees or consultants of such Party or its pre- existing Affiliates.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf540dc16ee91451785fd98309f0f8415" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.53._Cost_of_Goods_or_COGS_means_w"></a><font style="font-weight: bold;">1.53.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Cost of Goods</font>&#8221; or &#8220;<font style="font-weight: bold;">COGS</font>&#8221; means, with respect to any Licensed Product or Licensed System supplied by Metagenomi to Ionis
                  pursuant to <u>Article 8</u> (Manufacturing): 100% of: (a) [***]; and (b) [***]. The Cost of Goods will exclude any amounts incurred due to gross negligence or willful misconduct of Metagenomi, its Affiliates, or any Third Party. All
                  components of Cost of Goods will be allocated on a basis consistent with the Metagenomi&#8217;s Accounting Standards and consistent with the cost accounting policy applied by Metagenomi to other products that it produces. For clarity, the Cost
                  of Goods will not include any cost or expense already paid for by Ionis pursuant to this Agreement or any other agreement between the Parties or their Affiliates.</div>
              </td>
            </tr>

        </table>
        <div style="text-align: justify; text-indent: 0.05pt; margin-right: 5.6pt; margin-left: 50.95pt;"><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z0b6b1f7a4c304859b6853d3adae93ebd" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.54._Cover_Covers_or_Covered_me"></a><font style="font-weight: bold;">1.54.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Cover</font>,&#8221; &#8220;<font style="font-weight: bold;">Covers</font>,&#8221; or &#8220;<font style="font-weight: bold;">Covered</font>&#8221; means, as to a compound or product and Patent Right,
                  that, in the absence of a license granted under, or ownership of, such Patent Right, the making, using, keeping, selling, offering for sale, or importation of such compound or product would infringe such Patent Right or, as to a pending
                  claim included in such Patent Right, the making, using, keeping, selling, offering for sale, or importation of such compound or product would infringe such Patent Right if such pending claim were to issue in an issued patent without
                  modification.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="z7a3f9960b1e94f388ef8f49ccd6047fa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.55._Development_or_Develop_means_"></a><font style="font-weight: bold;">1.55.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Development</font>&#8221; or &#8220;<font style="font-weight: bold;">Develop</font>&#8221; means, with respect to any product, any and all internal and external research, development,
                  pharmacovigilance activities, and regulatory activities regarding such product, including (a) research, process development, non-clinical testing, toxicology, non-clinical activities, IND-enabling studies, and Clinical Trials, and (b)
                  preparation, submission, review, and development of data or information for the purpose of submission to a Regulatory Authority to obtain authorization to conduct Clinical Trials and to obtain, support, or maintain Regulatory Approval of
                  such product, but excluding any activities directed to Manufacturing, Medical Affairs, or Commercialization. Development will include research, development, and regulatory activities for additional presentations or indications for a
                  product after receipt of Regulatory Approval of such product, including Clinical Trials initiated following receipt of Regulatory Approval or any Clinical Trial to be conducted after receipt of Regulatory Approval that was mandated by the
                  applicable Regulatory Authority as a condition of such Regulatory Approval with respect to an approved indication (such as post-marketing approval studies and observational studies, if required by any Regulatory Authority in any country
                  in the Territory to support or maintain Regulatory Approval for a product in such country, including any phase IV studies). &#8220;<font style="font-weight: bold;">Develop</font>,&#8221; &#8220;<font style="font-weight: bold;">Developing</font>,&#8221; and &#8220;<font style="font-weight: bold;">Developed</font>&#8221; will be construed accordingly.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze8f34757522e4914a6f8b65c16eba643" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.56._Development_Candidate_means_a_th"></a><font style="font-weight: bold;">1.56.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Development Candidate</font>&#8221; means a therapeutic agent that is selected by Ionis for further Development and Commercialization in accordance with its customary internal
                  process and pursuant to <u>Section 2.2.6</u> (Delivery of Development Candidate; Development Candidate Report).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z64d9e4069f5f41cbb2e4e10f1f880c8b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.57._Development_Candidate_Report_has"></a><font style="font-weight: bold;">1.57.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Development Candidate Report</font>&#8221; has the meaning set forth in <u>Section 2.2.6</u> (Delivery of Development Candidate; Development Candidate Report).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="za1e994d69188435f994bad9851aaeebb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.58._Development_Cost_Share_Notice_ha"></a><font style="font-weight: bold;">1.58.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 9.3</u> (Option Exercise Fee).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z6e352b5ed7614f08b9a04810469fe479" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.59._Development_Supply_Agreement_has"></a><font style="font-weight: bold;">1.59.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Development Supply Agreement</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Metagenomi Supply Term).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7d8b00f1f07a43b98f8cdde4c9477039" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.60._Disclosing_Party_has_the_meaning"></a><font style="font-weight: bold;">1.60.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Disclosing Party</font>&#8221; has the meaning set forth in <u>Section 11.1.1</u> (General).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf491446f7ec74622803d4d70b6b2b627" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.61._Distracted_Party_has_the_meaning"></a><font style="font-weight: bold;">1.61.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Distracted Party</font>&#8221; has the meaning set forth in <u>Section 3.6.2</u> (Acquisition of Distracting Product).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z3cd76ae1e33b4b4c88f7d185002bb92d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.62._Distracting_Product_has_the_mean"></a><font style="font-weight: bold;">1.62.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Distracting Product</font>&#8221; has the meaning set forth in <u>Section 3.6.2</u> (Acquisition of Distracting Product).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z29b13a569cd540ef87f8a6f7e609dd7a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.63._Divest_means_with_respect_to_a_"></a><font style="font-weight: bold;">1.63.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means, with respect to a Distracting Product, [***].</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc1aa006c958447e3b061c3a630243fb4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.64._Drug_Discovery_Activities_has_th"></a><font style="font-weight: bold;">1.64.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Drug Discovery Activities</font>&#8221; has the meaning set forth in <u>Section 2.2.1</u> (Initial Drug Discovery Plan).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z1d4ba81ed6144fc3b83f0530dea6970d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.65._Drug_Discovery_Budget_has_the_me"></a><font style="font-weight: bold;">1.65.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Drug Discovery Budget</font>&#8221; has the meaning set forth in <u>Section 2.2.1</u> (Initial Drug Discovery Plan).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="za799eb0b58834873b2e3ed7d41e8d07b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.66._Drug_Discovery_Plan_has_the_mean"></a><font style="font-weight: bold;">1.66.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Drug Discovery Plan</font>&#8221; has the meaning set forth in <u>Section 2.2.1</u> (Initial Drug Discovery Plan).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.67._Drug_Discovery_Program_means_on"></a><font style="font-weight: bold;">1.67.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Drug Discovery Program</font>&#8221; means, on a Collaboration Target-by-Collaboration Target basis, the program of Development undertaken for a Collaboration Target, as set
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              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.68._Drug_Discovery_Term_has_the_mean"></a><font style="font-weight: bold;">1.68.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Drug Discovery Term</font>&#8221; has the meaning set forth in <u>Section 2.2.7</u> (Drug Discovery Term).</div>
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            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.69._Effective_Date_has_the_meaning_s"></a><font style="font-weight: bold;">1.69.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Effective Date</font>&#8221; has the meaning set forth in the Preamble.</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.70._EMA_means_the_European_Medicines"></a><font style="font-weight: bold;">1.70.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">EMA</font>&#8221; means the European Medicines Agency or any successor agency or authority thereto.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.71._Enabled_Delivery_has_the_meaning"></a><font style="font-weight: bold;">1.71.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in Section 3 [***] of the Exploratory Research Plan attached hereto as <u>Schedule 2.3.1</u> (Exploratory Research Plan).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.72._Encumbered_Proposed_Metagenomi_Ta"></a><font style="font-weight: bold;">1.72.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Encumbered Proposed Metagenomi Target</font>&#8221; has the meaning set forth in <u>Section 2.7.3(a)</u> (Encumbered Targets).</div>
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            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
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        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.73._Encumbered_Target_has_the_meanin"></a><font style="font-weight: bold;">1.73.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Encumbered Target</font>&#8221; has the meaning set forth in <u>Section 2.1.4(a)</u> (Encumbered Targets).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.74._Encumbrance_means_any_and_all_li"></a><font style="font-weight: bold;">1.74.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Encumbrance</font>&#8221; means any and all liens, encumbrances, charges, mortgages, security interests, hypothecations, easements, rights-of-way or encroachments of any nature
                  whatsoever.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.75._European_Union_or_EU_means_a"></a><font style="font-weight: bold;">1.75.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">European Union</font>&#8221; or &#8220;<font style="font-weight: bold;">EU</font>&#8221; means (a) all countries or territories that are officially part of the European Union, as constituted
                  from time to time, and (b) the United Kingdom.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.76._Exclusivity_Field_means_with_re"></a><font style="font-weight: bold;">1.76.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exclusivity Field</font>&#8221; means, with respect to a Drug Discovery Program, (a) [***] and (b) [***].</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z40078a960e1c48c4902bb1ebbfa49c94" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.77._Executive_Officer_has_the_meanin"></a><font style="font-weight: bold;">1.77.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Executive Officer</font>&#8221; has the meaning set forth in <u>Section 15.1.1</u> (Escalation).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.78._Existing_Potential_Ionis_In-Licen"></a><font style="font-weight: bold;">1.78.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Existing Potential Ionis In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.7.2</u> (Existing Potential Ionis In-License Agreements).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.79._Existing_Potential_Metagenomi_In-"></a><font style="font-weight: bold;">1.79.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Existing Potential Metagenomi In-License Agreement</font>&#8221; has the meaning set forth in <u>Section</u><u> 9.7.1</u> (Effective Date Licensed Technology; Existing
                  Metagenomi In-License Agreements).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.80._Expedited_Dispute_means_any_disp"></a><font style="font-weight: bold;">1.80.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Expedited Dispute</font>&#8221; means any dispute (a) that a Party elects pursuant to <u>Section 4.6.3(b)</u> (Resolution by Baseball Arbitration) to refer to resolution
                  pursuant to <u>Section 15.1.3</u> (Expedited Dispute Resolution), (b) regarding the determination of any final definitive terms of any Co- Development and Co-Commercialization Agreement pursuant to <u>Section 5.2</u> (Development and
                  Commercialization of the Co-Co Products; Opt-Down Right), (c) regarding the royalty rate or royalty term for any reversion royalty pursuant to <u>Section 14.3.6(c)</u> (Reversion Royalties), or (d) regarding any other provision of this
                  Agreement that the Parties agree to designate as an Expedited Dispute.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.81._Exploit_means_with_respect_to_a"></a><font style="font-weight: bold;">1.81.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploit</font>&#8221; means, with respect to any product, to Develop, have Developed, make, have made, use, have used, perform Medical Affairs, have performed Medical Affairs,
                  offer for sale, have offered for sale, sell, have sold, export, have exported, import, have imported, Manufacture, have Manufactured, Commercialize, have Commercialized, or otherwise exploit such product. &#8220;<font style="font-weight: bold;">Exploitation</font>&#8221;
                  and &#8220;<font style="font-weight: bold;">Exploiting</font>&#8221; will be construed accordingly.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.82._Exploratory_Research_Activities_"></a><font style="font-weight: bold;">1.82.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploratory Research Activities</font>&#8221; has the meaning set forth in <u>Section 2.3.1</u> (Exploratory Research Plan).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb905a3f4949244e79ee5be87fd89ec38" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.83._Exploratory_Research_Budget_has_"></a><font style="font-weight: bold;">1.83.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploratory Research Budget</font>&#8221; has the meaning set forth in <u>Section 2.3.1</u> (Exploratory Research Plan).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.84._Exploratory_Research_Plan_has_th"></a><font style="font-weight: bold;">1.84.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploratory Research Plan</font>&#8221; has the meaning set forth in <u>Section 2.3.1</u> (Exploratory Research Plan).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zcc470ae185874f279d6e193882379c61" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.85._Exploratory_Research_Program_has"></a><font style="font-weight: bold;">1.85.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploratory Research Program</font>&#8221; has the meaning set forth in <u>Section 2.3.1</u> (Exploratory Research Plan).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="za03d6608da404c128b004c5ad946f7ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.86._Exploratory_Research_Term_has_th"></a><font style="font-weight: bold;">1.86.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Exploratory Research Term</font>&#8221; has the meaning set forth in <u>Section 2.3.3</u> (Exploratory Research Term).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7ceb8355f42e4a40b42700de5803e8ea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.87._FDA_means_the_United_States_Food"></a><font style="font-weight: bold;">1.87.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">FDA</font>&#8221; means the United States Food and Drug Administration and any successor agency or authority thereto.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.88._FDC_Act_means_the_United_States"></a><font style="font-weight: bold;">1.88.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">FD&amp;C Act</font>&#8221; means the United States Food, Drug, and Cosmetic Act, as amended, and the rules and regulations promulgated thereunder, as may be in effect from time
                  to time.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
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          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.89._Field_means_with_respect_to_a_g"></a><font style="font-weight: bold;">1.89.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Field</font>&#8221; means, with respect to a given Drug Discovery Program, [***].</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z48593b388b184c20aeeeb3be08bd8a4b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.90._Firewall_Procedures_has_the_mean"></a><font style="font-weight: bold;">1.90.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Firewall Procedures</font>&#8221; has the meaning set forth in <u>Section 3.6.2</u> (Acquisition of Distracting Product).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z93c90c38633e4bcd9f9865866e83d1fc" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.91._First_Commercial_Sale_means_on_a"></a><font style="font-weight: bold;">1.91.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">First Commercial Sale</font>&#8221; means on a Licensed Product-by-Licensed Product and country-by- country basis, the first sale of a Licensed Product by Ionis, its Affiliate,
                  or its Sublicensee to a Third Party resulting in a Net Sale in a particular country; <font style="font-style: italic;">provided </font>that the following will not constitute a First Commercial Sale: (a) any sale of a Licensed Product to
                  a Ionis Affiliate or Sublicensee; (b) any sale of a Licensed Product for use in Clinical Trials, pre-clinical studies, or other Development activities at below market price; (c) the disposal or transfer of a Licensed Product for a <font style="font-style: italic;">bona fide </font>charitable purpose; or (d) compassionate use and &#8220;named patient sales.&#8221;</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7f7042b5d0744aaa8a3f2f9b4774fe19" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.92._Follow-On_Product_means_with_re"></a><font style="font-weight: bold;">1.92.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means, with respect to an Ionis Program and an Ionis Product Development Milestone Event, [***].</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="za99b0eb682c84ca5bdac56fa9091553a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.93._Force_Majeure_has_the_meaning_se"></a><font style="font-weight: bold;">1.93.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Force Majeure</font>&#8221; has the meaning set forth in <u>Section 15.11</u> (Force Majeure).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z5cde4fb6bf774708beef10bf7b612e6c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.94._FTE_has_the_meaning_set_forth_in"></a><font style="font-weight: bold;">1.94.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">FTE</font>&#8221; has the meaning set forth in <u>Section 1.95</u> (FTE Rate).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.95._FTE_Rate_means_an_annual_rate_of"></a><a name="z_bookmark160"></a><font style="font-weight: bold;">1.95.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">FTE Rate</font>&#8221; means an annual rate of $[***] for the time of an employee for a full-time equivalent (&#8220;<font style="font-weight: bold;">FTE</font>&#8221;) person year
                  (consisting of a total of 1,800 hours per annum) carrying out research, scientific, or technical work under this Agreement, prorated on a daily basis. Without limiting the foregoing, the FTE Rate will be adjusted annually for each
                  Calendar Year after the Calendar Year ending December 31, 2022 to be equal to the FTE Rate for the preceding Calendar Year plus [***]. The FTE Rate [***].</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.96._Gene_Editing_means_site-specific"></a><font style="font-weight: bold;">1.96.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Gene Editing</font>&#8221; means [***].</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.97._Governmental_Authority_means_any"></a><font style="font-weight: bold;">1.97.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Governmental Authority</font>&#8221; means any arbitrator, court, judicial, legislative, administrative or regulatory authority, commission, department, board, bureau, or body,
                  or other government authority or instrumentality or any Person exercising executive, legislative, judicial, regulatory, or administrative functions of or pertaining to government, whether foreign or domestic, whether federal, state,
                  provincial, municipal, or other.</div>
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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.98._Guide_RNA_means_any_single-_or_d"></a><font style="font-weight: bold;">1.98.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Guide RNA</font>&#8221; means any single- or double-stranded polynucleotide (including any analogue, variant, or mimic thereof) used for genome sequence site-specific targeting
                  of a Gene Editing protein.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.99._Increased_Cost_Notice_has_the_me"></a><font style="font-weight: bold;">1.99.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.2.4(c)</u> (Incremental Development Costs).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.100._Incremental_Development_Costs_h"></a><font style="font-weight: bold;">1.100.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.2.4(c)</u> (Incremental Development Costs).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.101._IND_means_an_investigational_ne"></a><font style="font-weight: bold;">1.101.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">IND</font>&#8221; means an investigational new drug application filed with the FDA with respect to a Licensed Product, or an equivalent application filed with the Regulatory
                  Authority of a country in the Territory other than the U.S. (such as an application for a Clinical Trial authorization in the EU).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.102._Indemnitee_has_the_meaning_set_"></a><font style="font-weight: bold;">1.102.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Indemnitee</font>&#8221; has the meaning set forth in <u>Section 13.4</u> (Conditions to Indemnification).</div>
              </td>
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        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.103._Infringement_has_the_meaning_se"></a><font style="font-weight: bold;">1.103.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Infringement</font>&#8221; has the meaning set forth in <u>Section 10.3.1</u> (Notification).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.104._Initial_Interest_Notice_has_the"></a><font style="font-weight: bold;">1.104.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.2.4(c)</u> (Incremental Development Costs).</div>
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            </tr>

        </table>
        <div> <br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.105._Initiation_means_with_respect_"></a><font style="font-weight: bold;">1.105.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Initiation</font>&#8221; means, with respect to any Clinical Trial, the date on which the first subject in such trial receives his or her initial dose in such Clinical Trial.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.106._Insolvency_Event_has_the_meanin"></a><font style="font-weight: bold;">1.106.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Insolvency Event</font>&#8221; has the meaning set forth in <u>Section 14.2.3</u> (Termination for Insolvency).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.107._Intellectual_Property_Rights_me"></a><font style="font-weight: bold;">1.107.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Intellectual Property Rights</font>&#8221; means any Know-How, Patent Rights, Trademarks, copyrights, trade secrets, and any other intellectual property rights however
                  denominated throughout the world.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.108._Internal_Costs_means_for_any_p"></a><font style="font-weight: bold;">1.108.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Internal Costs</font>&#8221; means, for any period, the product obtained by multiplying (a) the actual total FTEs (or portion thereof) devoted to the performance of activity
                  under this Agreement during such period, by (b) the applicable FTE Rate.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z4df33ea5c6ee4df59fe7c08fd9aa86c0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.109._Ionis_has_the_meaning_set_forth"></a><font style="font-weight: bold;">1.109.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Ionis</font>&#8221; has the meaning set forth in the Preamble.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z4140618c1a2844d693fdab19c8705963" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.110._Ionis_Background_Technology_has"></a><font style="font-weight: bold;">1.110.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Background Technology</font>&#8221; has the meaning set forth in <u>Section 2.7.1</u> (Option Grant).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.111._Ionis_Collaboration_Know-How_ha"></a><font style="font-weight: bold;">1.111.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ionis Collaboration Technology).</div>
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            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z5e49c0cad7d64ca1a0d385c49a98f26b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.112._Ionis_Collaboration_Patent_Right"></a><font style="font-weight: bold;">1.112.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ionis Collaboration Technology).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z19521454c68840ca85586b5a3dea718b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.113._Ionis_Collaboration_Technology_"></a><font style="font-weight: bold;">1.113.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Collaboration Technology</font>&#8221; has the meaning set forth in <u>Section 10.1.2(b)</u> (Ionis Collaboration Technology).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf166015314784387afc140c815599970" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.114._Ionis_Competitors_means_the_T"></a><a name="z_bookmark161"></a><font style="font-weight: bold;">1.114.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Ionis [***]</font>&#8221; means [***].</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z1cbbcb62bfea44f188ca94cb47de8f89" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.115._Ionis_Field_means_all_therapeut"></a><font style="font-weight: bold;">1.115.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Field</font>&#8221; means all therapeutic, prophylactic, palliative, analgesic, and diagnostic uses in humans utilizing oligonucleotides that bind to RNA, which such
                  oligonucleotides are subject to a Valid Claim of a Patent Right Controlled by Ionis.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb0338ff73e254885ba93364772c75b27" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.116._Ionis_Indemnitees_has_the_meani"></a><font style="font-weight: bold;">1.116.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Indemnitees</font>&#8221; has the meaning set forth in <u>Section 13.2</u> (Indemnification of Ionis by Metagenomi).</div>
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            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z9f8964e9be0e4af3b4303c1788bbb64a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.117._Ionis_In-License_Agreement_mean"></a><font style="font-weight: bold;">1.117.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis In-License Agreement</font>&#8221; means (a) any Existing Potential Ionis In-License Agreement that becomes an Ionis In-License Agreement pursuant to <u>Section 9.7.2</u>
                  (Existing Potential Ionis In- License Agreements) and (b) any New Ionis In-License Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z1d1d276003fd4f2cae507dbd3df32bb2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.118._Ionis_IP_Option_has_the_meaning"></a><font style="font-weight: bold;">1.118.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis IP Option</font>&#8221; has the meaning set forth in <u>Section 2.7.1</u> (Option Grant).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z3ae79ff87b254e4cb29a3d668f20e15c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.119._Ionis_IP_Option_Effective_Date_"></a><font style="font-weight: bold;">1.119.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis IP Option Effective Date</font>&#8221; has the meaning set forth in <u>Section 2.7.3(b)</u> (Effects if a Proposed Metagenomi Target is not an Encumbered Proposed
                  Metagenomi Target).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z9d8fab17dbd742369530824742da2732" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.120._Ionis_Knowledge_means_the_know"></a><font style="font-weight: bold;">1.120.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis&#8217; Knowledge</font>&#8221; means the knowledge, after reasonable investigation (including consultation with Ionis&#8217; outside intellectual property counsel), of the following:
                  [***] as of the applicable date.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z47261d2baf2f49a69286ab9ee67e3dec" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.121._Ionis_Licensed_Know-How_means_a"></a><font style="font-weight: bold;">1.121.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Licensed Know-How</font>&#8221; means all Know-How that is Controlled by Ionis or any of its Affiliates as of the Effective Date or during the Term (other than Joint
                  Collaboration Know-How) that is necessary or reasonably useful to perform the Metagenomi Activities.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7a1cd0f91ecf4e2f9f54139da6c7d7d0" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.122._Ionis_Licensed_Patent_Rights_me"></a><font style="font-weight: bold;">1.122.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Licensed Patent Rights</font>&#8221; means any Patent Rights Controlled by Ionis or any of its Affiliates that Cover any Ionis Licensed Know-How.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z97ccc2cb956848358ecc99c4ed8b22ec" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.123._Ionis_Licensed_Technology_means"></a><font style="font-weight: bold;">1.123.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Licensed Technology</font>&#8221; means Ionis Licensed Know-How and Ionis Licensed Patent Rights.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
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          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.124._Ionis_Product_Development_Milest"></a><font style="font-weight: bold;">1.124.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Development Milestone Event</font>&#8221; has the meaning set forth in <u>Section 9.4.1</u> (Ionis Product Development Milestone Payments).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.125._Ionis_Product_Development_Milest"></a><font style="font-weight: bold;">1.125.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Development Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 9.4.1</u> (Ionis Product Development Milestone Payments).</div>
              </td>
            </tr>

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        <div><br>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.126._Ionis_Product_Regulatory_Milesto"></a><font style="font-weight: bold;">1.126.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Regulatory Milestone Event</font>&#8221; has the meaning set forth in <u>Section 9.4.2</u> (Ionis Product Regulatory Milestone Payments).</div>
              </td>
            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.127._Ionis_Product_Regulatory_Milesto"></a><font style="font-weight: bold;">1.127.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Regulatory Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 9.4.2</u> (Ionis Product Regulatory Milestone Payments).</div>
              </td>
            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.128._Ionis_Product_Sales_Milestone_Ev"></a><font style="font-weight: bold;">1.128.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Sales Milestone Event</font>&#8221; has the meaning set forth in <u>Section 9.4.3</u> (Ionis Product Sales Milestone Payment).</div>
              </td>
            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.129._Ionis_Product_Sales_Milestone_Pa"></a><font style="font-weight: bold;">1.129.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Product Sales Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 9.4.3</u> (Ionis Product Sales Milestone Payment).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.130._Ionis_Products_means_any_Licens"></a><font style="font-weight: bold;">1.130.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Products</font>&#8221; means any Licensed Products that are the subject of an Ionis Program.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.131._Ionis_Programs_means_each_Drug_"></a><font style="font-weight: bold;">1.131.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Ionis Programs</font>&#8221; means each Drug Discovery Program for which Metagenomi does not exercise its Co-Co Option prior to the expiration of the applicable Co-Co Option Period or which Metagenomi opts
                  out in accordance with <u>Section 5.4</u> (Metagenomi Opt-Out).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.132._Ionis_Proprietary_Toolbox_of_Che"></a><font style="font-weight: bold;">1.132.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Proprietary Toolbox of Chemical Modifications</font>&#8221; means [***] that is Covered by an Ionis Toolbox Patent.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.133._Ionis-Prosecuted_Patent_Rights_"></a><font style="font-weight: bold;">1.133.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis-Prosecuted Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.2.1(a)</u>.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.134._Ionis_Records_has_the_meaning_s"></a><font style="font-weight: bold;">1.134.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Records</font>&#8221; has the meaning set forth in <u>Section 9.13.1</u> (Books and Records).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.135._Ionis_Royalties_has_the_meaning"></a><font style="font-weight: bold;">1.135.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Royalties</font>&#8221; has the meaning set forth in <u>Section 9.6.1</u> (Ionis Royalty Rates).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.136._Ionis_Royalty_Rates_has_the_mea"></a><font style="font-weight: bold;">1.136.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Ionis Royalty Rates</font>&#8221; has the meaning set forth in <u>Section 9.6.1</u> (Ionis Royalty Rates).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.137._Ionis_Royalty_Report_has_the_me"></a><font style="font-weight: bold;">1.137.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Ionis Royalty Report</font>&#8221; has the meaning set forth in <u>Section 9.6.4</u> (Ionis Royalty Reports).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.138._Ionis_Toolbox_Patent_means_any_"></a><font style="font-weight: bold;">1.138.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Ionis Toolbox Patent</font>&#8221; means any Patent Right Controlled by Ionis as of the Effective Date or during the Collaboration Term that [***].</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.139._Joint_Collaboration_Know-How_ha"></a><font style="font-weight: bold;">1.139.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Joint Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(c)</u> (Joint Collaboration Technology).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.140._Joint_Collaboration_Patent_Right"></a><font style="font-weight: bold;">1.140.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Joint Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(c)</u> (Joint Collaboration Technology).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.141._Joint_Collaboration_Technology_"></a><font style="font-weight: bold;">1.141.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Joint Collaboration Technology</font>&#8221; has the meaning set forth in <u>Section 10.1.2(c)</u> (Joint Collaboration Technology).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zee2c4155541e40f5a53a2e1ae3be6485" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.142._Joint_Research_Committee_or_JR"></a><font style="font-weight: bold;">1.142.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Joint Research Committee</font>&#8221; or &#8220;<font style="font-weight: bold;">JRC</font>&#8221; has the meaning set forth in <u>Section 4.3.1</u> (Formation and Purpose of the JRC).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.143._Joint_Steering_Committee_or_JS"></a><font style="font-weight: bold;">1.143.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Joint Steering Committee</font>&#8221; or &#8220;<font style="font-weight: bold;">JSC</font>&#8221; has the meaning set forth in <u>Section 4.1.1</u> (Formation and Purpose of the JSC).</div>
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            </tr>

        </table>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.144._Know-How_means_any_information_"></a><font style="font-weight: bold;">1.144.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Know-How</font>&#8221; means any information and materials, including records, discoveries, improvements, modifications, processes, techniques, methods, assays, chemical or
                  biological materials, designs, protocols, formulas, data (including physical data, chemical data, toxicology data, animal data, raw data, clinical data, and analytical and quality control data), dosage regimens, control assays, product
                  specifications, marketing, pricing and distribution costs, inventions, algorithms, technology, forecasts, profiles, strategies, plans, results in any form whatsoever, know-how and trade secrets (in each case, patentable, copyrightable or
                  otherwise).</div>
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            </tr>

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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.145._Licensed_Know-How_means_any_Kno"></a><font style="font-weight: bold;">1.145.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensed Know-How</font>&#8221; means any Know-How that is Controlled by Metagenomi or any of its Affiliates as of the Effective Date or during the Term (including Metagenomi
                  Collaboration Know- How, but excluding Joint Collaboration Know-How) that is necessary or reasonably useful to (a) perform the activities under any Collaboration Program Plan or (b) Exploit any Licensed System or Licensed Product.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.146._Licensed_Patent_Right_means_any"></a><a name="z_bookmark162"></a><font style="font-weight: bold;">1.146.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensed Patent Right</font>&#8221; means any Patent Right Controlled by Metagenomi or any of its Affiliates as of the Effective Date or during the Term (including Metagenomi
                  Collaboration Patent Rights, but excluding Joint Collaboration Patent Rights) that are necessary or reasonably useful to (a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;perform any activities under any Collaboration Program Plan or (b) Exploit any Licensed System or
                  Licensed Product. The Licensed Patent Rights as of the Effective Date are set forth on <u>Schedule 1.146</u> (Licensed Patent Rights); <font style="font-style: italic;">provided </font>that any Patent Right that otherwise meets this
                  definition will be deemed a Licensed Patent Right even if such Patent Right is not included on <u>Schedule 1.146</u> (Licensed Patent Rights).</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.147._Licensed_Product_means_any_ther"></a><font style="font-weight: bold;">1.147.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensed Product</font>&#8221; means any therapeutic product, medical therapy, preparation or substance, comprising or employing a Licensed System, in any form or formulation,
                  and whether alone or together with one or more other therapeutically active ingredients, delivery devices, or other components. All Licensed Products comprising the same Licensed System will be considered the same Licensed Product under
                  this Agreement.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.148._Licensed_Systems_means_with_re"></a><font style="font-weight: bold;">1.148.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensed Systems</font>&#8221; means, with respect to a Drug Discovery Program, (a) a Gene Editing protein and a Guide RNA that (i) is designed to modulate the Collaboration
                  Target for such Drug Discovery Program and (ii) either (A) was discovered or Developed by Metagenomi prior to the designation of such Collaboration Target or (B) is discovered or Developed pursuant to the Drug Discovery Plan for such Drug
                  Discovery Program, including any Development Candidate for such Drug Discovery Program or (b) any modification or derivative of any Gene Editing protein or Guide RNA described in clause (a).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.149._Licensed_Technology_means_all_L"></a><font style="font-weight: bold;">1.149.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensed Technology</font>&#8221; means all Licensed Know-How and Licensed Patent Rights and Metagenomi&#8217;s interest in the Joint Collaboration Technology.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.150._Licensee_has_the_meaning_set_fo"></a><font style="font-weight: bold;">1.150.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensee</font>&#8221; has the meaning set forth in <u>Section 15.10.1</u>.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.151._Licensing_Party_has_the_meaning"></a><font style="font-weight: bold;">1.151.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Licensing Party</font>&#8221; has the meaning set forth in <u>Section 15.10.1</u>.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.152._Losses_has_the_meaning_set_fort"></a><font style="font-weight: bold;">1.152.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Losses</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification of Metagenomi by Ionis).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.153._MAA_means_any_new_drug_applicat"></a><font style="font-weight: bold;">1.153.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">MAA</font>&#8221; means any new drug application or other marketing authorization application, in each case, filed with the applicable Regulatory Authority in a country or other
                  regulatory jurisdiction (and all supplements and amendments thereto), which application is required to commercially market or sell a pharmaceutical or biologic product in such country or jurisdiction, including (a) all New Drug
                  Applications and BLAs submitted to the FDA in the United States in accordance with the FD&amp;C Act with respect to a pharmaceutical product, (b) all MAAs submitted to (i) the EMA under the centralized EMA filing procedure in the EU or
                  (ii) a Regulatory Authority in any EU country if the centralized EMA filing procedure is not used to gain Regulatory Approval in such country, (c) all New Drug Applications submitted to the National Medical Products Administration, or (d)
                  any analogous application or submission with any Regulatory Authority in any other country or regulatory jurisdiction.</div>
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            </tr>

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.154._Major_European_Markets_means_ea"></a><font style="font-weight: bold;">1.154.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Major European Markets</font>&#8221; means each of France, Germany, Spain, Italy, and the United Kingdom.</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.155._Major_Market_means_each_of_Japa"></a><font style="font-weight: bold;">1.155.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Major Market</font>&#8221; means each of Japan, the Major European Markets, and the US.</div>
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            </tr>

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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.156._Manufacture_or_Manufacturing_"></a><font style="font-weight: bold;">1.156.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Manufacture</font>&#8221; or &#8220;<font style="font-weight: bold;">Manufacturing</font>&#8221; means with respect to any product, any and all activities directed to manufacturing,
                  processing, packaging, labeling, filling, finishing, assembly, quality assurance, quality control, analyses, testing and release, shipping, supply, or storage of such product (or any raw materials, components or process steps involving
                  such product or any companion diagnostic), placebo, or comparator agent, as the case may be, including qualification, validation, and scale-up, pre-clinical, clinical, and commercial manufacture and analytic development, product
                  characterization, and stability testing, but excluding any activities directed to Development, Medical Affairs, or Commercialization. &#8220;<font style="font-weight: bold;">Manufacturing</font>&#8221; and &#8220;<font style="font-weight: bold;">Manufactured</font>&#8221;
                  will be construed accordingly.</div>
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            </tr>

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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.157._Manufacturing_Know-How_has_the_"></a><font style="font-weight: bold;">1.157.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Manufacturing Know-How</font>&#8221; has the meaning set forth in <u>Section 8.5</u> (Manufacturing After the Metagenomi Supply Term).</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.158._Manufacturing_Technology_Transfe"></a><font style="font-weight: bold;">1.158.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Manufacturing Technology Transfer</font>&#8221; has the meaning set forth in <u>Section 8.5</u> (Manufacturing After the Metagenomi Supply Term).</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.159._Medical_Affairs_means_any_and_a"></a><font style="font-weight: bold;">1.159.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Medical Affairs</font>&#8221; means any and all activities customarily conducted by the medical affairs department of a pharmaceutical or biotechnology company commercializing products similar to the
                  Licensed Products, including communications with key opinion leaders, medical education, symposia, advisory boards (to the extent related to medical affairs or clinical guidance), activities performed in connection with patient
                  registries, and other medical programs and communications, including educational grants, research grants (including conducting investigator-initiated studies), patient advocacy, and charitable donations to the extent related to medical
                  affairs and not related to activities that involve the promotion, marketing, sale, or other Commercialization of a product and that are not conducted by or on behalf of a Party&#8217;s or any of its Affiliates&#8217; medical affairs departments.</div>
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            </tr>

        </table>
        <div><br>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.160._Metagenomi_has_the_meaning_set_"></a><font style="font-weight: bold;">1.160.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi</font>&#8221; has the meaning set forth in the Preamble.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.161._Metagenomi_Activities_has_the_m"></a><font style="font-weight: bold;">1.161.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Activities</font>&#8221; has the meaning set forth in <u>Section 3.2.1(a)</u> (Metagenomi Activities License Grant).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.162._Metagenomi_Collaboration_Cost_Re"></a><font style="font-weight: bold;">1.162.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Cost Reports</font>&#8221; has the meaning set forth in <u>Section 2.5.1</u> (Reimbursement by Ionis).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.163._Metagenomi_Collaboration_Know-Ho"></a><font style="font-weight: bold;">1.163.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Know-How</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Metagenomi Collaboration Technology).</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.164._Metagenomi_Collaboration_Patent_"></a><font style="font-weight: bold;">1.164.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Metagenomi Collaboration Technology).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.165._Metagenomi_Collaboration_Technol"></a><font style="font-weight: bold;">1.165.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Metagenomi Collaboration Technology</font>&#8221; has the meaning set forth in <u>Section 10.1.2(a)</u> (Metagenomi Collaboration Technology).</div>
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            </tr>

        </table>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.166._Metagenomi_Competitors_means_"></a><a name="z_bookmark163"></a><font style="font-weight: bold;">1.166.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Metagenomi [***]</font>&#8221; means [***].</div>
              </td>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.167._Metagenomi_Drug_Discovery_Costs"></a><font style="font-weight: bold;">1.167.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Metagenomi Drug Discovery Costs</font>&#8221; has the meaning set forth in <u>Section 2.5.1</u> (Reimbursement by Ionis).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.168._Metagenomi_Exploratory_Research_"></a><font style="font-weight: bold;">1.168.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Exploratory Research Costs</font>&#8221; has the meaning set forth in <u>Section 2.5.1</u> (Reimbursement by Ionis).</div>
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            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zdcc596da729440599316cdb0fc335e3c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.169._Metagenomi_Field_means_all_ther"></a><font style="font-weight: bold;">1.169.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Field</font>&#8221; means all therapeutic, prophylactic, palliative, analgesic, and diagnostic uses in humans through the use of the Metagenomi Platform.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.170._Metagenomi_In-License_Agreements"></a><font style="font-weight: bold;">1.170.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi In-License Agreements</font>&#8221; means (a) any Existing Potential Metagenomi In-License Agreement that becomes a Metagenomi In-License Agreement pursuant to <u>Section


                    9.7.1</u> (Effective Date Licensed Technology; Existing Metagenomi In-License Agreements) and (b) any New Metagenomi In-License Agreement.</div>
              </td>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.171._Metagenomi_Indemnitees_has_the_"></a><font style="font-weight: bold;">1.171.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Indemnitees</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification of Metagenomi by Ionis).</div>
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        </table>
        <div><br>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.172._Metagenomis_Knowledge_means_th"></a><font style="font-weight: bold;">1.172.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi&#8217;s Knowledge</font>&#8221; means the knowledge, after reasonable investigation (including consultation with Metagenomi&#8217;s outside intellectual property counsel), of the
                  following: [***] or, in each case, their functional equivalent.</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.173._Metagenomi_Platform_means_Metag"></a><font style="font-weight: bold;">1.173.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Metagenomi Platform</font>&#8221; means [***].</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.174._Metagenomi_Platform_Know-How_me"></a><font style="font-weight: bold;">1.174.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Platform Know-How</font>&#8221; means any Know-How within Metagenomi Platform as of the Effective Date or during the Term.</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.175._Metagenomi_Platform_Patent_Right"></a><a name="z_bookmark164"></a><font style="font-weight: bold;">1.175.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Platform Patent Rights</font>&#8221; means any Patent Rights Controlled by Metagenomi or its Affiliates as of the Effective Date or during the Term that Cover any
                  Metagenomi Platform Know-How. The Metagenomi Platform Patent Rights Controlled by Metagenomi or any of its Affiliates as of the Effective Date are listed in <u>Schedule 1.175</u> (Metagenomi Platform Patent Rights); <font style="font-style: italic;">provided </font>that any Patent Right that otherwise meets this definition will be deemed a Metagenomi Platform Patent Right even if such Patent Right is not included on <u>Schedule 1.175</u> (Metagenomi
                  Platform Patent Rights).</div>
              </td>
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        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z090fa8144083452096c93700c1429f34" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.176._Metagenomi_Platform_Technology_"></a><font style="font-weight: bold;">1.176.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Platform Technology</font>&#8221; means the Metagenomi Platform Patent Rights and the Metagenomi Platform Know-How.</div>
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            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.177._Metagenomi_Product_means_any_th"></a><font style="font-weight: bold;">1.177.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Product</font>&#8221; means any therapeutic product, medical therapy, preparation or substance, comprising or employing a Metagenomi System and discovered by
                  Metagenomi, in any form or formulation, and whether alone or together with one or more other therapeutically active ingredients, delivery devices, or other components. All Metagenomi Products comprising the same Metagenomi System will be
                  considered the same Metagenomi Product under this Agreement.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.178._Metagenomi_Product_Milestone_Eve"></a><font style="font-weight: bold;">1.178.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Product Milestone Event</font>&#8221; has the meaning set forth in <u>Section 9.10.1</u> (Metagenomi Product Milestone Payments).</div>
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            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc1f3d00e5c234bf480fca603b8820a44" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.179._Metagenomi_Product_Milestone_Pay"></a><font style="font-weight: bold;">1.179.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Product Milestone Payment</font>&#8221; has the meaning set forth in <u>Section 9.10.1</u> (Metagenomi Product Milestone Payments).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z62dd4455f9bd435681e5b4e759f1b0ff" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.180._Metagenomi-Prosecuted_Patent_Rig"></a><font style="font-weight: bold;">1.180.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi-Prosecuted Patent Rights</font>&#8221; has the meaning set forth in <u>Section 10.2.2</u> (Metagenomi-Prosecuted Patent Rights).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="z4656958a71224d26bf36ee63c938211f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.181._Metagenomi_Records_has_the_mean"></a><font style="font-weight: bold;">1.181.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Records</font>&#8221; has the meaning set forth in <u>Section 9.13.1</u> (Books and Records).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc0a7c65230c94062935d2d421eb19056" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.182._Metagenomi_Royalties_has_the_me"></a><font style="font-weight: bold;">1.182.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Royalties</font>&#8221; has the meaning set forth in <u>Section 9.10.3(a)</u> (Metagenomi Royalty Rates)</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z3e38823fc14d4ca1a9e378224547dd98" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.183._Metagenomi_Royalty_Rate_has_the"></a><font style="font-weight: bold;">1.183.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Royalty Rate</font>&#8221; has the meaning set forth in <u>Section 9.10.3(a)</u> (Metagenomi Royalty Rates)</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zbae01282f49d4bcf8f1be036b24cc868" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.184._Metagenomi_Royalty_Report_has_t"></a><font style="font-weight: bold;">1.184.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Royalty Report</font>&#8221; has the meaning set forth in <u>Section 9.10.4</u> (Metagenomi Royalty Reports).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zdcb5c673ca004875a8e80242e779f351" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.185._Metagenomi_Royalty_Term_means_"></a><font style="font-weight: bold;">1.185.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Royalty Term</font>&#8221; means, on a Metagenomi Product-by-Metagenomi Product and country-by-country basis, the period during the Term ending on the latest of (a)
                  [***] following the First Commercial Sale (applied <font style="font-style: italic;">mutatis mutandis</font>) of a Metagenomi Product in a country, (b) the expiration of the last Valid Claim of a Patent Right within the Ionis Background
                  Technology Covering such Metagenomi Product in such country, or (c) the expiration of any applicable Regulatory Exclusivity obtained for such Metagenomi Product in such country.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z9dd9c8f9ecf84af4845eccaecc5e08da" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.186._Metagenomi_Supply_Term_has_the_"></a><font style="font-weight: bold;">1.186.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Supply Term</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Metagenomi Supply Term).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze4871478d7244244a7916f36f9b1804c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.187._Metagenomi_System_means_a_Gene_"></a><font style="font-weight: bold;">1.187.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi System</font>&#8221; means a Gene Editing protein and a Guide RNA that is designed to modulate a Metagenomi Target.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf208788b151843e89a8a9dd8748800f5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.188._Metagenomi_Target_means_each_ta"></a><font style="font-weight: bold;">1.188.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Metagenomi Target</font>&#8221; means each target for which Metagenomi exercises an Ionis IP Option pursuant to <u>Section 2.7</u> (Ionis Proprietary Toolbox of Chemical
                  Modifications).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z858ec510a5a542ac8fb143b44c55188d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.189._MG_Manufactured_Components_has_"></a><font style="font-weight: bold;">1.189.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">MG Manufactured Components</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Metagenomi Supply Term).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z10e2c49ce49b4b44aa5b3b8cdd7f2b9f" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.190._Net_Sales_means_the_gross_invoi"></a><a name="z_bookmark165"></a><font style="font-weight: bold;">1.190.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Net Sales</font>&#8221; means the gross invoiced amount for (a) Ionis Products sold by Ionis, its Affiliates, or Sublicensees or (b) Metagenomi Products sold by Metagenomi, its
                  Affiliates or Sublicensees, in each case ((a) and (b) (the &#8220;<font style="font-weight: bold;">Selling Party</font>&#8221;)), to the extent recognized in the ordinary course of business as revenue by the Selling Party on an accrual basis in
                  accordance with United States Generally Accepted Accounting Principles or, in the case of non-United States sales, other applicable accounting standards after deduction of the following amounts:</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zc797cad6685e43968d0f7524ea3319aa" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="za_normal_and_customary_trade_quantity"></a>(a)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">normal and customary trade, quantity or prompt settlement discounts (including initial launch stocking discounts, chargebacks, and allowances) actually allowed, <font style="font-style: italic;">provided </font>that


                  such discounts are not applied disproportionately to such Licensed Product or Metagenomi Product when compared to the other products of the Selling Party;</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc21f1f3b483842c0b7ff1e63d62bd051" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zb_amounts_repaid_or_credited_by_reason"></a>(b)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">amounts repaid or credited by reason of rejection, returns or recalls of goods, rebates or <font style="font-style: italic;">bona fide </font>price reductions determined by the Selling Party in good
                  faith;</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z7abd60af12ec439a91f21f996a7b1ba6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zc_rebates_and_similar_payments_made_wi"></a>(c)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">rebates and similar payments made with respect to sales paid for by any Governmental Authority such as, by way of illustration and not in limitation of the Parties&#8217; rights hereunder, Federal or state
                  Medicaid, Medicare or similar state program in the United States or equivalent governmental program in any other country;</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <table cellspacing="0" cellpadding="0" id="zfff7602ef0684b03ab806192992fdd4c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zd_refunds_or_clawbacks_of_a_portion_of"></a>(d)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">refunds or clawbacks of a portion of payments previously paid by the Selling Party for not achieving a predetermined metric or term in an outcome-based contracts;</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z8aa18df9e07b4e678afa7ed48aba3106" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="ze_any_invoiced_amounts_that_are_not_co"></a>(e)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">any invoiced amounts that are not collected by the Selling Party, including bad debts, (applied to Net Sales in the period in which such receivables are written off), provided that any such amounts
                  subsequently collected will be included in Net Sales for the period collected;</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z70b0baf602ef4ddabb6ab69f74cab910" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zf_excise_taxes_value_added_taxes_sal"></a>(f)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">excise taxes, value added taxes, sales taxes, consumption taxes and other similar taxes (excluding any income, franchise, or withholding taxes), customs duties, customs levies and import fees imposed on the
                  sale, importation, use or distribution of the Licensed Product, including fees paid pursuant to Section 9008 of the Patient Protection and Affordable Care Act that the Selling Party allocate to sales of the Licensed Product or Metagenomi
                  Product (as applicable) in accordance with such Selling Party&#8217;s standard policies and procedures consistently applied across its products, as applicable; and</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze213d86480c9448c823973c5afdb20e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 90pt;"><br>
              </td>
              <td style="width: 36pt; vertical-align: top;"><a name="zg_an_allowance_for_transportation_cost"></a>(g)</td>
              <td style="vertical-align: top;">
                <div style="text-align: justify;">an allowance for transportation costs, distribution expenses, special packaging, insurance charges, and storage and warehousing costs.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <div style="text-align: justify; margin-left: 54pt; text-indent: 36pt;"><a name="Net_Sales_including_any_deductions_wil"></a>Net Sales (including any deductions) will be calculated using the Selling Party&#8217;s internal audited systems used to report
          such sales as adjusted for any of the items above not taken into account in such systems, fairly applied and as employed on a consistent basis throughout such Selling Party&#8217;s operations. To the extent any accrued amounts used in the calculation
          of Net Sales are estimates, such estimates will be trued-up to actuals (including that, for any estimates of deductions that are later decreased, the difference will be added back to Net Sales). In no event will any particular amount identified
          above be deducted more than once in calculating Net Sales (<font style="font-style: italic;">i.e</font>., no &#8220;double counting&#8221; of deductions).</div>
        <div style="margin-left: 54pt; text-indent: 36pt;">&#160;</div>
        <div style="text-align: justify; margin-left: 54pt; text-indent: 36pt;">In the case of any sale or other disposal of a product between or among such Party or its Affiliates or Sublicensees for resale, Net Sales will be calculated only on the value
          charged or invoiced on the first arm&#8217;s-length sale thereafter to a Third Party (other than a Sublicensee). In the case of any sale that is not invoiced or is delivered before invoice, Net Sales will be calculated at the time all the revenue
          recognition criteria under such Party&#8217;s Accounting Standards are met. In the case of any sale or other disposal for value, such as barter or counter-trade, of any Licensed Product or Metagenomi Product (as applicable), or part thereof, other than
          in an arm&#8217;s-length transaction exclusively for money, Net Sales will be calculated on the value of the non-cash consideration received or the fair market price (if higher) of such Licensed Product(s) or Metagenomi Product(s) (as applicable) in
          the country of sale or disposal. Notwithstanding the foregoing, the following will not be included in Net Sales: (1) sales between or among a Party and its Affiliates or Sublicensees (but Net Sales will include sales to the first Third Party
          (other than a Sublicensee) by a Party or its Affiliates or Sublicensees); and (2) any named patient sales or any sale or other distribution at cost or less than cost for use in any Clinical Trial, for <font style="font-style: italic;">bona fide
          </font>charitable purposes, test marketing program, or for compassionate use.</div>
        <div style="margin-left: 54pt; text-indent: 36pt;">&#160;</div>
        <div style="text-align: justify; margin-left: 54pt; text-indent: 36pt;">Solely for purposes of calculating Net Sales, if the Selling Party sells a Licensed Product or Metagenomi Product (as applicable) in the form of a combination product
          containing a Licensed System or Metagenomi System (as applicable) and one or more other therapeutically or prophylactically active ingredients or delivery devices that is not a Licensed System or Metagenomi System (as applicable) (&#8220;<font style="font-weight: bold;">Other Product</font>&#8221;) (whether combined in a single formulation or package, as applicable, or formulated separately but packaged under a single label approved by a Regulatory Authority and sold together for a single
          price) (such combination product, a &#8220;<font style="font-weight: bold;">Combination Product</font>&#8221;), Net Sales of such Combination Product for the purpose of determining the payments due to the other Party pursuant to this Agreement will be
          calculated by [***]. If the gross selling price of a Licensed Product or Metagenomi Product (as applicable) containing such Licensed System or Metagenomi System (as applicable) in such country when sold separately in finished form (<font style="font-style: italic;">i.e.</font>, without the other active ingredients or delivery device) can be determined but the gross selling price of the Other Product in such country cannot be determined, then Net Sales in such country for
          purposes of determining royalty payments will be calculated by [***]. If such separate sales are not made in a country, then Net Sales will be calculated by [***].</div>
        <div style="text-align: justify; margin-left: 54pt; text-indent: 36pt;"> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-align: justify; margin-left: 54pt; text-indent: 36pt;">If a license agreement or collaboration agreement that is negotiated in an arm&#8217;s length transaction with an Sublicensee includes a definition of &#8220;Net Sales&#8221; that differs in any
          material respect from the definition contained in this <u>Section 1.190</u> (Net Sales), then the Parties will discuss such material differences and will use reasonable efforts to negotiate in good faith any reasonable modifications to this <u>Section



            1.190</u> (Net Sales) that are necessary to avoid any ambiguity in the calculation of the royalty payment due to a Party under this Agreement for sales of Licensed Products or Metagenomi Products by such Sublicensee.</div>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zacfac87d811d4ed58514f21a68f296cb" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.191._New_Base_Editing_Modality_means"></a><font style="font-weight: bold;">1.191.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">[***]</font>&#8221; means [***].</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb21dfdabfe0c48eb96a8cce61db57339" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.192._New_In-License_Agreement_has_th"></a><font style="font-weight: bold;">1.192.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">New In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.2 </u>(Acceptance of a Proposed New In-License Agreement).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb06bb8c738834b8f9ba87ebac4dbe7c1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.193._New_Ionis_In-License_Agreement_"></a><font style="font-weight: bold;">1.193.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">New Ionis In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.2 </u>(Acceptance of a Proposed New In-License Agreement).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z323d3b74d49b40848c22a2af91a42f6b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.194._New_Metagenomi_In-License_Agreem"></a><font style="font-weight: bold;">1.194.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">New Metagenomi In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.2</u> (Acceptance of a Proposed New In-License Agreement).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z6caf187afa4548d1a1f47009085b86e4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.195._Non-Withholding_Party_has_the_m"></a><font style="font-weight: bold;">1.195.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Non-Withholding Party</font>&#8221; has the meaning set forth in <u>Section 9.17</u> (Withholding Taxes).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z129b97bb1a554021bea20d33b7d0590a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.196._Opt-Down_Right_has_the_meaning_"></a><font style="font-weight: bold;">1.196.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Opt-Down Right</font>&#8221; has the meaning set forth in <u>Section 5.2</u> (Development and Commercialization of the Co-Co Products; Opt-Down Right).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z4fa1ae6580924e2ca8fe801e7b95b0ad" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.197._Opt-Out_Date_has_the_meaning_se"></a><font style="font-weight: bold;">1.197.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Opt-Out Date</font>&#8221; has the meaning set forth in <u>Section 5.4</u> (Metagenomi Opt-Out).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zd8dbb7ccc44c4a69af11752589c1df90" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.198._Opt-Out_Period_has_the_meaning_"></a><font style="font-weight: bold;">1.198.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Opt-Out Period</font>&#8221; has the meaning set forth in <u>Section 5.4</u> (Metagenomi Opt-Out).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zc61d617ab926427290a02d2a92bc6716" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.199._Opt-Out_Right_has_the_meaning_s"></a><font style="font-weight: bold;">1.199.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Opt-Out Right</font>&#8221; has the meaning set forth in <u>Section 5.4</u> (Metagenomi Opt-Out).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf60434b6b2954289b08cc2dd515a53e5" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.200._Option_Exercise_Fee_has_the_mea"></a><font style="font-weight: bold;">1.200.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Option Exercise Fee</font>&#8221; has the meaning set forth in <u>Section 9.3</u> (Option Exercise Fee).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf94ae3eee053477193e91bd2d2319fe1" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.201._Option_Exercise_Notice_has_the_"></a><font style="font-weight: bold;">1.201.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Option Exercise Notice</font>&#8221; has the meaning set forth in <u>Section 2.7.2</u> (Option Exercise).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z858e8aedc2be45b5bf5c3f459d473b72" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.202._Option_Package_has_the_meaning_"></a><font style="font-weight: bold;">1.202.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Option Package</font>&#8221; has the meaning set forth in <u>Section 5.1.2</u> (Option Period).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z2e389ae7b939462099539d3f87504d99" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.203._Option_Term_has_the_meaning_set"></a><font style="font-weight: bold;">1.203.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Option Term</font>&#8221; has the meaning set forth in <u>Section 2.7.2</u> (Option Exercise).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z908ae7d45f65437f9193d80234dc78ba" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.204._Other_Product_has_the_meaning_s"></a><font style="font-weight: bold;">1.204.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Other Product</font>&#8221; has the meaning set forth in <u>Section 1.190</u> (Net Sales).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.205._Out-of-Pocket_Costs_means_with"></a><font style="font-weight: bold;">1.205.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Out-of-Pocket Costs</font>&#8221; means, with respect to certain activities hereunder, direct expenses actually paid or payable by a Party or its Affiliates to Third Parties and
                  specifically identifiable and incurred to conduct such activities, but excluding any costs that are included in the FTE Rate.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z92a4e682935c4709b51fd51b0981c87b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.206._Party_has_the_meaning_set_forth"></a><font style="font-weight: bold;">1.206.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Party</font>&#8221; has the meaning set forth in the Preamble.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zb539614ab4b5457bad06833be79d5601" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.207._Party_Vote_has_the_meaning_set_"></a><font style="font-weight: bold;">1.207.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Party Vote</font>&#8221; has the meaning set forth in <u>Section 4.6.1</u> (Committee Decisions).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.208._Patent_Rights_means_all_rights"></a><font style="font-weight: bold;">1.208.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Patent Rights</font>&#8221; means all rights, title, and interests in and to (a) all national, regional, and international patents and patent applications filed in any country of
                  the world including provisional patent applications and all supplementary protection certificates, (b) all patent applications filed either from such patents, patent applications, or provisional applications or from an application
                  claiming priority to any of the foregoing, including any continuation, continuation-in part, divisional, provisional, converted provisionals and continued prosecution applications, or any substitute applications, (c) any patent issued
                  with respect to or in the future issued from any such patent applications, including utility models, petty patents, design patents and certificates of invention, and (d) any and all extensions or restorations by existing or future
                  extension or restoration mechanisms, including revalidations, reissues, reexaminations and extensions (including any supplementary protection certificates and the like) of the foregoing patents or patent applications.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf4ccf46790d346dca3a3dab3d3425b70" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.209._Payments_has_the_meaning_set_fo"></a><font style="font-weight: bold;">1.209.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Payments</font>&#8221; has the meaning set forth in <u>Section 9.17</u> (Withholding Taxes).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z84102e21047d41e28ee3ffdbad968aaf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.210._Person_means_an_individual_sol"></a><font style="font-weight: bold;">1.210.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Person</font>&#8221; means an individual, sole proprietorship, partnership, limited partnership, limited liability partnership, corporation, limited liability company, business
                  trust, joint stock company, trust, incorporated association, joint venture or similar entity or organization, including any Governmental Authority (or any department, agency, or political subdivision thereof).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="za7c140e4ed1d4fcda1a912dd1aa0e56a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.211._Phase_III_Clinical_Trial_means_"></a><font style="font-weight: bold;">1.211.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Phase III Clinical Trial</font>&#8221; means a Clinical Trial that the FDA permits to be conducted under an open IND and that is performed to gain evidence with statistical
                  significance of the efficacy of such product in a target population, and to obtain expanded evidence of safety for such product that is needed to evaluate the overall benefit-risk relationship of such product, to form the basis for
                  approval of an MAA by a Regulatory Authority and to provide an adequate basis for physician labeling, in a manner that meets the requirements of 21 C.F.R. &#167; 312.21(c), as amended (or its successor regulation), or, with respect to any
                  other country or region, the equivalent of such a Clinical Trial in such other country or region. Notwithstanding anything to the contrary set forth in this Agreement, treatment of patients as part of an expanded access program,
                  compassionate sales or use program (including named patient program or single patient program), or an indigent program, in each case, will not be included in determining whether or not a Clinical Trial is a Phase III Clinical Trial or
                  whether a patient has been dosed thereunder.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z747d5d82dbd34297b1dda7819f5c6c0d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.212._Pivotal_Clinical_Trial_means_an"></a><font style="font-weight: bold;">1.212.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Pivotal Clinical Trial</font>&#8221; means any (a) Phase III Clinical Trial, or (b) other Clinical Trial of a product on a sufficient number of patients, the results of which,
                  together with prior data and information concerning such product, are intended to be or otherwise are sufficient, without any additional Clinical Trial, to meet the evidentiary standard for demonstrating the safety, purity, efficacy, and
                  potency of such active substance of such product established by a Regulatory Authority in any particular jurisdiction, as evidenced by finalized meeting minutes or another written statement from such Regulatory Authority, and that is
                  intended to support, or otherwise supports, the filing of an MAA by a Regulatory Authority in such jurisdiction (including any bridging study). Notwithstanding any provision to the contrary set forth in this Agreement, treatment of
                  patients as part of an expanded access program, compassionate sales or use program (including named patient program or single patient program), or an indigent program, in each case, will not be included in determining whether or not a
                  Clinical Trial is a Pivotal Clinical Trial or whether a patient has been dosed thereunder.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z08aa73ddd5444123bb8b37f90c4cdade" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.213._Pre-Existing_Ionis_Restriction_"></a><font style="font-weight: bold;">1.213.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Pre-Existing Ionis Restriction</font>&#8221; has the meaning set forth in <u>Section 2.7.3(a)</u> (Encumbered Targets).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z0f372288f5e24731837508ba27666f15" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.214._Pre-Existing_Restriction_has_th"></a><font style="font-weight: bold;">1.214.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Pre-Existing Restriction</font>&#8221; has the meaning set forth in <u>Section 2.1.4(a)</u> (Encumbered Targets).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="ze909e02f56c841428ef298da70d463db" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.215._Pricing_Approval_means_in_any_"></a><font style="font-weight: bold;">1.215.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Pricing Approval</font>&#8221; means, in any country where a Governmental Authority authorizes reimbursement for, or approves or determines pricing for, pharmaceutical products,
                  receipt (or, if required to make such authorization, approval or determination effective, publication) of such reimbursement authorization or pricing approval or determination.</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.216._Proceeding_means_any_action_su"></a><font style="font-weight: bold;">1.216.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proceeding</font>&#8221; means any action, suit, litigation, arbitration, proceeding (including any civil, criminal, administrative, investigative or appellate proceeding),
                  prosecution, contest, hearing, inquiry, inquest, audit, examination or investigation that is, has been or may in the future be commenced, brought, conducted or heard at law or in equity or before any Governmental Authority.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z9fd153bfd9b846b0b22411802a0f1ad3" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.217._Product-Specific_Know-How_means"></a><font style="font-weight: bold;">1.217.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Product-Specific Know-How</font>&#8221; means any Licensed Know-How that specifically relates to (a) a Licensed System or Licensed Product, (b) any method of making a Licensed
                  System or Licensed Product, or (c) the use of a Licensed System or Licensed Product and no other products that are not Licensed Systems or Licensed Products.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z62b59cb4654143aa93c9e4d48616a33c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.218._Product-Specific_Patent_Right_m"></a><font style="font-weight: bold;">1.218.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Product-Specific Patent Right</font>&#8221; means any Licensed Patent Right that specifically claims (a) a Licensed System or Licensed Product, (b) any method of making a
                  Licensed System or Licensed Product, or (c) the use of a Licensed System or Licensed Product and no other products that are not Licensed Systems or Licensed Products.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z15bab9857f90416fb624b25179a4fdc6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.219._Proposed_Metagenomi_Target_has_"></a><font style="font-weight: bold;">1.219.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed Metagenomi Target</font>&#8221; has the meaning set forth in <u>Section 2.7.2</u> (Option Exercise).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z898f753d2d854647a2ba480cc47288ac" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.220._Proposed_Metagenomi_Target_Notic"></a><font style="font-weight: bold;">1.220.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed Metagenomi Target Notice</font>&#8221; has the meaning set forth in <u>Section 2.7.2</u> (Option Exercise).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z56bc1f67658543948ef17b76dae708d8" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.221._Proposed_New_Editing_Modality_h"></a><font style="font-weight: bold;">1.221.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.2.4(c)</u> (Incremental Development Costs).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zf10f8657427e49518bf9d186111392a4" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.222._Proposed_New_In-License_Agreemen"></a><font style="font-weight: bold;">1.222.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed New In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.1</u> (Proposed New In-License Agreements).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zc673ec8617c94400b863f2bae9af82cf" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.223._Proposed_New_Ionis_In-License_Ag"></a><font style="font-weight: bold;">1.223.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed New Ionis In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.1</u> (Proposed New In-License Agreements).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="zf2c6a689ea664a6f8ae16c75fdf7cd9e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.224._Proposed_New_Metagenomi_In-Licen"></a><font style="font-weight: bold;">1.224.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed New Metagenomi In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 9.8.1</u> (Proposed New In-License Agreements).</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="z1d547fcf366b401ca50a14bb5e36d872" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.225._Proposed_Replacement_Target_has"></a><font style="font-weight: bold;">1.225.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed Replacement Target</font>&#8221; has the meaning set forth in <u>Section 2.1.3(d)</u> (Substitution Procedure).</div>
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            </tr>

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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.226._Proposed_Target_means_any_a_A"></a><font style="font-weight: bold;">1.226.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Proposed Target</font>&#8221; means any (a) Additional Wave 1 Target, (b) Wave 2 Target, or (c) Proposed Replacement Target.</div>
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            </tr>

        </table>
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              <td style="width: 54.05pt; vertical-align: top; font-weight: bold;">1.227.</td>
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                <div style="text-align: justify;"><a name="z1.227.__Prosecuting_Party_means_with_"></a>&#8220;<font style="font-weight: bold;">Prosecuting Party</font>&#8221; means, with respect to any Patent Right, the Party that is responsible for the Prosecution
                  and Maintenance of such Patent Right pursuant to <u>Section 10.2.1</u> (Ionis-Prosecuting Patent Rights) or <u>Section 10.2.2</u> (Metagenomi-Prosecuted Patent Rights), as applicable.</div>
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            </tr>

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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.228._Prosecution_and_Maintenance_or_"></a><font style="font-weight: bold;">1.228.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Prosecution and Maintenance</font>&#8221; or &#8220;<font style="font-weight: bold;">Prosecute and Maintain</font>&#8221; means, with regard to a Patent Right, the preparing, filing,
                  prosecuting, and maintenance of such Patent Right, as well as handling re-examinations and reissues with respect to such Patent Right, together with the conduct of interferences, derivation proceedings, the defense of oppositions,
                  post-grant patent proceedings (such as <font style="font-style: italic;">inter partes </font>review and post grant review), and other similar proceedings with respect to the particular Patent Right. For clarity, &#8220;<font style="font-weight: bold;">Prosecution and Maintenance</font>&#8221; or &#8220;<font style="font-weight: bold;">Prosecute and Maintain</font>&#8221; will not include any other enforcement actions taken with respect to a Patent Right.</div>
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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.229._Quarterly_Reimbursement_Payments"></a><font style="font-weight: bold;">1.229.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Quarterly Reimbursement Payments</font>&#8221; has the meaning set forth in <u>Section 2.5.1</u> (Reimbursement by Ionis).</div>
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            </tr>

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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.230._Receiving_Party_has_the_meaning"></a><font style="font-weight: bold;">1.230.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Receiving Party</font>&#8221; has the meaning set forth in <u>Section 11.1.1</u> (General).</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.231._Regulatory_Approval_means_with"></a><font style="font-weight: bold;">1.231.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Regulatory Approval</font>&#8221; means, with respect to a particular country or other regulatory jurisdiction in the Territory, any approval of an MAA or other approval,
                  product, or establishment license, registration, or authorization of the applicable Regulatory Authority necessary for the commercial marketing or sale of a pharmaceutical or biologic product in such country or other regulatory
                  jurisdiction, including, where applicable, Pricing Approval.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.232._Regulatory_Authority_means_wit"></a><font style="font-weight: bold;">1.232.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Regulatory Authority</font>&#8221; means, with respect to a country in the Territory, any national (e.g., the FDA), supra-national (e.g., the European Commission, the Council of
                  the European Union, or the EMA), regional, state or local regulatory agency, department, bureau, commission, council or other Governmental Authority involved in the granting of Regulatory Approvals or Pricing Approvals for pharmaceutical
                  products in such country or countries.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.233._Regulatory_Exclusivity_means_w"></a><font style="font-weight: bold;">1.233.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Regulatory Exclusivity</font>&#8221; means, with respect to a Licensed Product or Metagenomi Product (as applicable) in a country, any data exclusivity rights or other exclusive
                  right, other than a Patent Right, granted, conferred, or afforded by any Regulatory Authority in such country or otherwise under Applicable Law with respect to such Licensed Product or Metagenomi Product (as applicable) in such country,
                  which either confers exclusive marketing rights with respect to a product or prevents another party from using or otherwise relying on the data supporting the approval of the Regulatory Approval for a product without the prior written
                  authorization of the Regulatory Approval holder, as applicable, such as new chemical entity exclusivity, exclusivity associated with new Clinical Trials necessary to approval of a change (e.g., new indication or use), orphan drug
                  exclusivity, non-patent-related pediatric exclusivity, or any other applicable marketing or data exclusivity, including any such periods under national implementations in the EU of Article 10 of Directive 2001/83/EC, Article 14(11) of
                  Parliament and Council Regulation (EC) No 726/2004, Parliament and Council Regulation (EC) No 141/2000 on orphan medicines, Parliament and Council Regulation (EC) No 1901/2006 on medicinal products for pediatric use and all international
                  equivalents.</div>
              </td>
            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.234._Regulatory_Strategy_has_the_mea"></a><font style="font-weight: bold;">1.234.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Regulatory Strategy</font>&#8221; has the meaning set forth in <u>Section 7.1</u> (Regulatory Responsibility).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.235._Regulatory_Submissions_means_an"></a><font style="font-weight: bold;">1.235.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Regulatory Submissions</font>&#8221; means any regulatory application, submission, notification, communication, correspondence, registration, Regulatory Approval, and other
                  filing, made to, received from or otherwise conducted with a Regulatory Authority related to Developing, Manufacturing, obtaining marketing authorization, or otherwise Commercializing a product in a particular country or jurisdiction,
                  including all INDs, CTAs, BLAs, MAAs, and all applications for Regulatory Approval together with all supplements or amendments to any of the foregoing.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.236._Reimbursement_Cap_has_the_meani"></a><font style="font-weight: bold;">1.236.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Reimbursement Cap</font>&#8221; has the meaning has the meaning set forth in <u>Section 2.5.1</u> (Reimbursement by Ionis).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.237._Replacement_Target_Notice_has_t"></a><font style="font-weight: bold;">1.237.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Replacement Target Notice</font>&#8221; has the meaning set forth in <u>Section 2.1.3(d)</u> (Substitution Procedure).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.238._Requested_CMO_has_the_meaning_s"></a><font style="font-weight: bold;">1.238.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Requested CMO</font>&#8221; has the meaning set forth in <u>Section 8.1.2</u> (Requested CMO).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.239._Requested_CMO_Contract_has_the_"></a><font style="font-weight: bold;">1.239.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Requested CMO Contract</font>&#8221; has the meaning set forth in <u>Section 8.1.2</u> (Requested CMO).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.240._Residual_Knowledge_has_the_mean"></a><font style="font-weight: bold;">1.240.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Residual Knowledge</font>&#8221; has the meaning set forth in <u>Section 11.3</u> (Residual Knowledge).</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.241._Reversion_IP_In-License_Agreemen"></a><font style="font-weight: bold;">1.241.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Reversion IP In-License Agreement</font>&#8221; has the meaning set forth in <u>Section 14.3.6(b)</u> (Third Party Reversion IP).</div>
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        </table>
        <div> <br>
        </div>
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          <div class="BRPFPageBreak" style="page-break-after: always;">
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.242._Reversion_License_has_the_meani"></a><font style="font-weight: bold;">1.242.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Reversion License</font>&#8221; has the meaning set forth in <u>Section 14.3.6(a)</u> (Reversion License Grant).</div>
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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.243._Royalty_Bearing_Patent_Rights_m"></a><font style="font-weight: bold;">1.243.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Royalty Bearing Patent Rights</font>&#8221; means, with respect to any Licensed Product, all Licensed Patent Rights that Cover such Licensed Product and that are listed in the
                  then-current edition of the FDA&#8217;s Purple Book in connection with the Regulatory Approval of such Licensed Product, or in equivalent patent listings in any other country within the Territory.</div>
              </td>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.244._Royalty_Term_means_on_a_Licens"></a><font style="font-weight: bold;">1.244.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Royalty Term</font>&#8221; means, on a Licensed Product-by-Licensed Product and country-by-country basis, the period during the Term ending on the latest of (a) [***] following
                  the First Commercial Sale of a Licensed Product in a country, (b) the expiration of the last Valid Claim of the Royalty Bearing Patent Rights Covering such Licensed Product in such country, or (c) the expiration of any applicable
                  Regulatory Exclusivity obtained for such Licensed Product in such country.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.245._Second_Wave_1_Target_has_the_me"></a><font style="font-weight: bold;">1.245.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Second Wave 1 Target</font>&#8221; has the meaning set forth in <u>Section 2.1.1(b)</u> (Second Wave 1 Target).</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.246._Selling_Party_has_the_meaning_s"></a><font style="font-weight: bold;">1.246.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Selling Party</font>&#8221; has the meaning set forth in <u>Section 1.190</u> (Net Sales).</div>
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            </tr>

        </table>
        <div><br>
        </div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.247._Subcommittee_has_the_meaning_se"></a><font style="font-weight: bold;">1.247.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Subcommittee</font>&#8221; has the meaning set forth in <u>Section 4.2</u> (Subcommittees).</div>
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        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.248._Subcontractor_means_a_Third_Par"></a><font style="font-weight: bold;">1.248.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Subcontractor</font>&#8221; means a Third Party contractor engaged by a Party to perform certain obligations or exercise certain rights of such Party under this Agreement on a
                  fee-for-service basis (including Third Party Distributors, contract research organizations, or contract manufacturing organizations).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.249._Sublicensee_means_a_Third_Party"></a><font style="font-weight: bold;">1.249.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Sublicensee</font>&#8221; means a Third Party to whom a Party or any of its Affiliates grants a sublicense under the licenses granted to such Party under this Agreement, as
                  permitted herein, excluding all Subcontractors.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.250._Supply_Price_has_the_meaning_se"></a><font style="font-weight: bold;">1.250.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Supply Price</font>&#8221; has the meaning set forth in <u>Section 8.1.1</u> (Metagenomi Supply Term).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.251._Target_Selection_and_Substitutio"></a><font style="font-weight: bold;">1.251.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Target Selection and Substitution Period</font>&#8221; has the meaning set forth in <u>Section 2.1.4(b)</u> (Expiration of Pre-Existing Restrictions).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z5271c1ed3f9d4f62873bb5b8f22ab0a2" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.252._Target_Substitution_Period_has_"></a><font style="font-weight: bold;">1.252.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Target Substitution Period</font>&#8221; has the meaning set forth in <u>Section 2.1.3(a)</u> (Discretionary Substitutions).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.253._Technological_Infeasibility_has"></a><font style="font-weight: bold;">1.253.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Technological Infeasibility</font>&#8221; has the meaning set forth in <u>Section 2.1.3(b)</u> (Substitutions for Technological Infeasibility).</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.254._Term_has_the_meaning_set_forth_"></a><font style="font-weight: bold;">1.254.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Term</font>&#8221; has the meaning set forth in <u>Section 14.1</u> (Term).</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.255._Terminated_Combination_Products"></a><font style="font-weight: bold;">1.255.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Terminated Combination Products</font>&#8221; has the meaning set forth in <u>Section 14.3.7</u> (Reversion for Certain Combination Products).</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.256._Terminated_Country_means_a_an"></a><font style="font-weight: bold;">1.256.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Terminated Country</font>&#8221; means (a) any country in the Territory with respect to which this Agreement is terminated or expires pursuant to <u>Article 14</u> (Term and
                  Termination), and (b) in the event of termination or expiration of this Agreement in its entirety, all countries in the Territory.</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.257._Terminated_Products_means_a_a"></a><font style="font-weight: bold;">1.257.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Terminated Products</font>&#8221; means (a) any Licensed Product with respect to which this Agreement is terminated or expires pursuant to <u>Article 14</u> (Term and
                  Termination), and (b) in the event of termination or expiration of this Agreement in its entirety, all Licensed Products.</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.258._Territory_means_all_countries_o"></a><font style="font-weight: bold;">1.258.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Territory</font>&#8221; means all countries of the world and all territories and possessions thereof.</div>
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            </tr>

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        <div> <br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.259._Third_Party_means_any_Person_ot"></a><font style="font-weight: bold;">1.259.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party</font>&#8221; means any Person other than a Party or an Affiliate of a Party.</div>
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            </tr>

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        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.260._Third_Party_Claims_has_the_mean"></a><font style="font-weight: bold;">1.260.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party Claims</font>&#8221; has the meaning set forth in <u>Section 13.1</u> (Indemnification of Metagenomi by Ionis).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.261._Third_Party_Distributor_means_a"></a><font style="font-weight: bold;">1.261.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party Distributor</font>&#8221; means any Third Party that distributes (but does not Develop or Manufacture) a Licensed Product directly to customers.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.262._Third_Party_Expert_has_the_mean"></a><font style="font-weight: bold;">1.262.</font></td>
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                <div>&#8220;<font style="font-weight: bold;">Third Party Expert</font>&#8221; has the meaning set forth in <u>Section 15.1.3(a)</u>.</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.263._Third_Party_Infringement_Claim_"></a><font style="font-weight: bold;">1.263.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party Infringement Claim</font>&#8221; has the meaning set forth in <u>Section 10.4</u> (Defense of Claims Brought by Third Parties).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.264._Third_Party_IP_has_the_meaning_"></a><font style="font-weight: bold;">1.264.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party IP</font>&#8221; has the meaning set forth in <u>Section 9.6.2(c)</u> (Third Party Payments).</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.265._Third_Party_Payment_has_the_mea"></a><font style="font-weight: bold;">1.265.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Third Party Payment</font>&#8221; has the meaning set forth in <u>Section 9.6.2(c)</u> (Third Party Payments).</div>
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            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z4b6fb7a05ec7403d82a90372c12816ed" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.266._Trademarks_means_all_registered"></a><font style="font-weight: bold;">1.266.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Trademarks</font>&#8221; means all registered and unregistered trademarks, service marks, trade dress, trade names, logos, insignias, symbols, designs, and all other indicia of
                  ownership, and combinations thereof.</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <table cellspacing="0" cellpadding="0" id="ze4298fe1a196499b8e11201c861ce19d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.267._TTR_has_the_meaning_set_forth_i"></a><font style="font-weight: bold;">1.267.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 2.1.1(a)</u> (Initial Wave 1 Target).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.268._Ultra-Rare_Target_Population_ha"></a><font style="font-weight: bold;">1.268.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***] Target Population</font>&#8221; has the meaning set forth in <u>Section 9.5</u> (Ionis Products for [***] Target Populations).</div>
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            </tr>

        </table>
        <div><br>
        </div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.269._Unblocking_Field_means_a_with"></a><font style="font-weight: bold;">1.269.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Unblocking Field</font>&#8221; means [***].</div>
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        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.270._United_States_or_U.S._means_t"></a><font style="font-weight: bold;">1.270.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">United States</font>&#8221; or &#8220;<font style="font-weight: bold;">U.S.</font>&#8221; means the United States of America and all of its districts, territories and possessions.</div>
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        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.271._Upfront_Payment_has_the_meaning"></a><font style="font-weight: bold;">1.271.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Upfront Payment</font>&#8221; has the meaning set forth in <u>Section 9.1</u> (Upfront Payment).</div>
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        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.272._Valid_Claim_means_with_respect"></a><font style="font-weight: bold;">1.272.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Valid Claim</font>&#8221; means, with respect to a particular country, (a) a claim of any issued and unexpired patent in such country whose validity, enforceability, or
                  patentability has not been terminated by any of the following: (i) irretrievable lapse, abandonment, revocation, dedication to the public, or disclaimer; or (ii) a holding, finding, or decision of invalidity, unenforceability, or non-
                  patentability, from which decision no appeal can be further taken, or (b) a claim within a patent application in such country that has not been pending for more than seven years from the earliest date to which such claim or the applicable
                  patent application is entitled to claim priority and which claim has not been revoked, cancelled, withdrawn, held invalid, or abandoned.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.273._Warranty_Technology_means_a_w"></a><font style="font-weight: bold;">1.273.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Warranty Technology</font>&#8221; means (a) with respect to any representation or warranty made as of the Effective Date, (i) the Metagenomi Platform Technology in the Field, and
                  (ii) the Licensed Technology that is necessary or reasonably useful to Exploit Licensed Systems and Licensed Products in the Field that are directed to [***], and (b) with respect to any representation or warranty made as of the date on
                  which each new target becomes a Collaboration Target pursuant to <u>Section</u>&#160;<u>2.1.1(b)</u> (Second Wave 1 Target) or <u>Section 2.1.4(c)</u> (Effects if a Proposed Target is Available), the Licensed Technology that is necessary or
                  reasonably useful to Exploit Licensed Systems and Licensed Products in the Field that are directed to such Collaboration Target.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.274._Wave_1_Target_means_each_a_TT"></a><font style="font-weight: bold;">1.274.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Wave 1 Target</font>&#8221; means each (a) [***], (b) the Second Wave 1 Target, and (c) any Additional Wave 1 Target that Ionis designates in accordance with <u>Section 2.1.4(c)</u>
                  (Effects if a Proposed Target is Available).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
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              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.275._Wave_2_Target_has_the_meaning_s"></a><font style="font-weight: bold;">1.275.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Wave 2 Target</font>&#8221; has the meaning set forth in <u>Section 2.1.2</u> (Wave 2 Target Options).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.276._Wave_2_Target_Notice_has_the_me"></a><font style="font-weight: bold;">1.276.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Wave 2 Target Notice</font>&#8221; has the meaning set forth in <u>Section 2.1.2</u> (Wave 2 Target Options).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.277._Wave_2_Target_Selection_Fee_has"></a><font style="font-weight: bold;">1.277.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">[***]</font>&#8221; has the meaning set forth in <u>Section 9.2</u> ([***]).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.278._Wave_2_Target_Selection_Period_"></a><font style="font-weight: bold;">1.278.</font></td>
              <td style="width: auto; vertical-align: top;">
                <div>&#8220;<font style="font-weight: bold;">Wave 2 Target Selection Period</font>&#8221; has the meaning set forth in <u>Section 2.1.2</u> (Wave 2 Target Options).</div>
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            </tr>

        </table>
        <div>&#160;</div>
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            <tr>
              <td style="width: 54.05pt; vertical-align: top;"><a name="z1.279._Withholding_Party_has_the_meani"></a><font style="font-weight: bold;">1.279.</font></td>
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                <div style="text-align: justify;">&#8220;<font style="font-weight: bold;">Withholding Party</font>&#8221; has the meaning set forth in <u>Section 9.17</u> (Withholding Taxes).</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div class="BRPFPageBreak" style="page-break-after: always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-align: center; font-weight: bold;"><u>Schedule 1.114</u></div>
        <div><br>
        </div>
        <div style="text-align: center;">[***]</div>
        <div><br>
        </div>
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            <tr>
              <td style="width: 33pt;"><br>
              </td>
              <td style="width: 17.95pt; vertical-align: top; font-size: 12pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top;">
                <div>[***]</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zb5ac91f346c44f2aa6ebd2e96d55120b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 33pt;"><br>
              </td>
              <td style="width: 17.95pt; vertical-align: top; font-size: 12pt;">&#8226;</td>
              <td style="width: auto; vertical-align: top;">
                <div>[***]</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z2262b4777bcd4702933cc1efd968718c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
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      <div>&#160;</div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <table cellspacing="0" cellpadding="0" id="zfe3e7783a8b54d65a13719fca6743af6" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="zfcbac29648124700abed5de17f418133" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z3ecac967ca9e4868a83668ad90011665" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z23e322758c094ae1a3346b6cb216dd5b" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="ze40ad458e1c544bb95ef3e8f79d5747c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z3dba507e1bec49ae92de25f4108198ea" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="zbcbd5711aa5f420da5185e02aca582e9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <table cellspacing="0" cellpadding="0" id="z5d2ad41cbf7d496e9ae8c31295f53007" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="ze55dd04ccc294e9bba8c050b9a9e8b9e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="zb8b48afab02f4cc1ad51712a989c0725" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z8bd7312f2c614e15af742c221c279f6e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="zfeee921d198c47ddac8b8e4bf2978555" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="za0daadab52ed4b589b16e93871d5bad9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="zc00ac42c906b44988c9dedb3cded390a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 33pt;"><br>
            </td>
            <td style="width: 17.95pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <table cellspacing="0" cellpadding="0" id="z3ed02a4ccb694b7f8b1337a6ee785b30" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 32.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z1ed77c0ad27444b4a00947f345ea084c" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 32.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 2.1.1(a)</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">[***]</div>
      <div> <br>
      </div>
      <div>&#8220;[***]&#8221; is the [***].</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 2.2</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">[***] Drug Discovery Plan</div>
      <div><br>
      </div>
      <div style="text-align: center;">Attached<font style="font-style: italic;">.</font></div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; color: rgb(128, 128, 128); font-style: italic;"><a name="Active_130522044_1_Hummingbird_-_TTR_Dru"></a><font style="color: rgb(0, 0, 0); background-color: rgb(255, 255, 255); font-weight: normal; font-style: italic; font-variant: normal; text-transform: none;">Confidential</font></div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Schedule 2.2</div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-size: 12pt;"><font style="font-size: 10pt;">[***]</font><font style="font-size: 10pt; font-weight: bold;"> Drug Discovery Plan</font></div>
      <div><br>
      </div>
      <div style="font-weight: bold;">[***]</div>
      <div style="font-size: 12pt; font-weight: bold;"> <font style="font-size: 10pt;"><br>
        </font></div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 2.3.1</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">Exploratory Research Plan</div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center;">Attached<font style="font-style: italic;">.</font></div>
      <div style="text-align: center; font-style: italic;"><a name="Active_130522052_1_Hummingbird_-_Explora"></a>Confidential</div>
      <div><br>
      </div>
      <div style="text-align: center; font-weight: bold;">Schedule 2.3.1</div>
      <div style="text-align: center; font-weight: bold;"> <br>
      </div>
      <div style="text-align: center; font-weight: bold;">Exploratory Research Plan</div>
      <div style="text-indent: 33.2pt; margin-right: 169.1pt; margin-left: 179.25pt; font-size: 12pt; font-weight: bold;"> <font style="font-size: 10pt;"><br>
        </font></div>
      <div style="text-align: justify;">[***]</div>
      <div>&#160;</div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 8.2</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">Development Supply Agreement Key Terms</div>
      <div>&#160;</div>
      <div style="text-align: justify; margin-left: 54pt;">[***]</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z00ec842977e54fd9ad599d55a029257e" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="width: 25.3%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="width: 25.3%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***] <br>
              </div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
        <div style="page-break-after: always;" class="BRPFPageBreak">
          <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
      </div>
      <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

          <tr>
            <td style="width: 25.3%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>
          <tr>
            <td style="width: 25.3%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: center;">[***]</div>
            </td>
            <td style="width: 74.7%; vertical-align: top; border-left: 2px solid rgb(0, 0, 0); border-right: 2px solid rgb(0, 0, 0); border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
              <div style="text-align: justify; margin-left: 72pt;">[***]</div>
            </td>
          </tr>

      </table>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><a name="Ionis_-_Metagenomi_Collaboration_Agreeme"></a><u>Schedule 11.4</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">Press Release(s)</div>
      <div><br>
      </div>
      <div style="text-align: center;">Attached<font style="font-style: italic;">.</font></div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
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      <div><br>
      </div>
      <div>
        <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; color: #000000; width: 100%;" id="zc09dabb2f84947119cb41f5e14ee3a2a">

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                <div style="text-align: center;">&#160;<img src="image07.jpg"></div>
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                <div style="text-align: center;">&#160;<img src="image11.jpg"></div>
              </td>
            </tr>

        </table>
      </div>
      <div><br>
      </div>
      <div style="font-weight: bold; text-align: justify;">Ionis partners with Metagenomi to add gene editing to its broad technology platform</div>
      <div><br>
      </div>
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          <tr>
            <td style="width: 32.95pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8722;</td>
            <td style="width: auto; vertical-align: top;">
              <div style="font-style: italic; text-align: justify;">Collaboration with a leader in gene editing systems is Ionis&#8217; latest move to expand and diversify its technology</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 32.95pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8722;</td>
            <td style="width: auto; vertical-align: top;">
              <div style="font-style: italic; text-align: justify;">CRISPR-Cas gene editing is a natural extension of Ionis&#8217; innovative approach to delivering potentially transformative therapies</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
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          <tr>
            <td style="width: 32.95pt;"><br>
            </td>
            <td style="width: 18pt; vertical-align: top;">&#8722;</td>
            <td style="width: auto; vertical-align: top;">
              <div style="font-style: italic;">Ionis to hold webcast Nov. 14 at 8 a.m. Eastern Time</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="font-size: 12pt; text-align: justify;"><font style="font-size: 10pt; font-weight: bold;">CARLSBAD, Calif. and EMERYVILLE, Calif. Nov. 14, 2022 </font><font style="font-size: 10pt;">&#8211; <u>Ionis Pharmaceuticals,</u>&#160;<u>Inc.</u>&#160;(Nasdaq:
          IONS) and <u>Metagenomi</u>&#160;today announced that the companies have entered a collaboration that will leverage Ionis&#8217; extensive expertise in RNA-targeted therapeutics and Metagenomi&#8217;s versatile next-generation gene editing systems to pursue a
          mix of validated and novel genetic targets that have potential to expand therapeutic options for patients. The companies will jointly conduct research aimed initially at delivering investigational medicines for up to four genetic targets. Ionis
          has the right to add four more targets upon achievement of pre-determined development milestones.</font></div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">&#8220;Ionis was founded over 30 years ago to discover and develop novel, highly personalized medicines using our powerful RNA-targeting technology platform. This partnership with Metagenomi supports Ionis&#8217; strategic
        objective to advance our technology and expand our capabilities to deliver precision genetic medicines.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">Together, we can broaden the application of gene editing by leveraging Ionis&#8217; vast experience in nucleic acid therapeutics to optimize and extend the reach of gene editing for liver targets and to new tissues,&#8221; said
        Ionis Chief Executive Officer Brett P. Monia, Ph.D. &#8220;This alliance brings our two companies closer to delivering next-generation therapies with the potential to revolutionize the treatment of diseases.&#8221;</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">&#8220;Gene editing has the potential to transform chronic therapies into potentially curative treatments for patients who currently have limited options,&#8221; said Brian C. Thomas,</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">1</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">EMBARGOED UNTIL MONDAY, NOVEMBER 14 AT 6:05 A.M. EASTERN TIME</div>
      <div>&#160;</div>
      <div style="text-align: justify;">Ph.D., chief executive officer and founder of Metagenomi. &#8220;This collaboration is a strategic step to combine Metagenomi&#8217;s leading gene editing toolbox of diverse, specific and highly efficient nucleases, with Ionis&#8217;
        pioneering expertise of RNA-targeted therapeutics, to catalyze the next wave of in vivo gene editing applications. We continue to follow our strategy of partnering with the most experienced teams in the genetic medicines field that will allow us to
        transform the lives of patients.&#8221;</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">Under the terms of the agreement, Ionis will pay $80 million upfront to Metagenomi plus the potential for future milestone payments and royalties. Wells Fargo Securities acted as financial advisor to Ionis on the
        transaction.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-weight: bold; text-align: justify;">Webcast</div>
      <div><br>
      </div>
      <div style="text-align: justify;">Ionis will conduct a webcast on Nov. 14 at 8 a.m. Eastern Time to discuss this announcement and related activities. Interested parties may access the webcast [<font style="color: rgb(0, 0, 0);">here]. A webcast
          replay will be available for a limited time at the same address.</font></div>
      <div><br>
      </div>
      <div style="font-weight: bold; text-align: justify;">CRISPR Gene Editing</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">&#8220;CRISPR (clustered regularly interspaced short palindromic repeats) gene editing is a technology that modifies the sequence of DNA in cells utilizing a specific RNA-guided nuclease (Cas enzyme). Gene editing enzymes
        act as molecular word processors to correct the genetic code at the precise spot where it is malfunctioning.&#8221;</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-weight: bold; text-align: justify;">About Ionis Pharmaceuticals, Inc.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a
        premier late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming a leading,
        fully integrated biotechnology company.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">To learn more about Ionis, visit www.ionispharma.com and follow us on Twitter @ionispharma.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-weight: bold; text-align: justify;">About Metagenomi</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">Metagenomi is a gene editing company committed to developing potentially curative therapeutics by leveraging a proprietary toolbox of next-generation gene editing systems to accurately edit DNA where current
        technologies cannot. Our metagenomics- powered discovery platform and analytical expertise reveal novel cellular machinery sourced from otherwise unknown organisms. We adapt and forge these naturally</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">2</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="color: rgb(255, 0, 0); font-weight: bold;">EMBARGOED UNTIL MONDAY, NOVEMBER 14 AT 6:05 A.M. EASTERN TIME</div>
      <div>&#160;</div>
      <div style="text-align: justify;">evolved systems into powerful gene editing systems that are ultra-small, extremely efficient, highly specific and have a decreased risk of immune response. These systems fuel our pipeline of novel medicines and can
        be leveraged by partners. Our goal is to revolutionize gene editing for the benefit of patients around the world. For more information, please visit https://metagenomi.co/.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-weight: bold; text-align: justify;">Ionis&#8217; Forward-looking Statements</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">This press release includes forward-looking statements regarding Ionis&#8217; business and the therapeutic and commercial potential of Ionis&#8217; technologies and products in development. Any statement describing Ionis&#8217; goals,
        expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including but not limited to, those
        related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the
        endeavor of building a business around such medicines. Ionis&#8217; forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such
        forward-looking statements.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">Although Ionis&#8217; forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely
        on these forward-looking statements.</div>
      <div style="text-align: justify;">These and other risks concerning Ionis&#8217; programs are described in additional detail in Ionis&#8217; annual report on Form 10-K for the year ended Dec. 31, 2021, and the most recent Form 10-Q quarterly filing, which are on
        file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">In this press release, unless the context requires otherwise, &#8220;Ionis,&#8221; &#8220;Company,&#8221; &#8220;we,&#8221; &#8220;our,&#8221; and &#8220;us&#8221; refers to Ionis Pharmaceuticals and its subsidiaries.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="text-align: justify;">Ionis Pharmaceuticals&#174; is a trademark of Ionis Pharmaceuticals, Inc.</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-size: 12pt; text-align: justify;"><font style="font-size: 10pt; font-weight: bold;">Ionis Investor Contact: </font><font style="font-size: 10pt;"><u>info@ionisph.com</u>, 760-603-2331</font></div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-size: 12pt; text-align: justify;"><font style="font-size: 10pt; font-weight: bold;">Ionis Media Contact: </font><font style="font-size: 10pt;"><u>corporatecommunications@ionisph.com</u>, 760-603-4679</font></div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-size: 12pt; text-align: justify;"><font style="font-size: 10pt; font-weight: bold;">Metagenomi Investor Contact: </font><font style="font-size: 10pt;">Simon Harnest, simon@metagenomi.co</font></div>
      <div style="text-align: justify;">+1 (917) 403-1051</div>
      <div style="text-align: justify;">&#160;</div>
      <div style="font-size: 12pt; text-align: justify;"><font style="font-size: 10pt; font-weight: bold;">Metagenomi Media Contact: </font><font style="font-size: 10pt;">Ashlye Hodge, ashlye@metagenomi.co</font></div>
      <div style="text-align: justify;">+1 (510) 734-4409</div>
      <div><br>
      </div>
      <div class="BRPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
        <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;">3</font></div>
        <div class="BRPFPageBreak" style="page-break-after: always;">
          <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 12.2</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">Metagenomi Disclosure Schedule</div>
      <div><br>
      </div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <div>&#160;</div>
      <div>[***]:</div>
      <div>&#160;</div>
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              <div>[***].</div>
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          <tr>
            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="zb6c4a142b11e4653a75bc01959aaf06d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
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          <tr>
            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <div>&#160;</div>
      <div style="font-weight: bold;"><u>[***]</u></div>
      <div>&#160;</div>
      <div>[***]:</div>
      <div>&#160;</div>
      <table cellspacing="0" cellpadding="0" id="z43c17ec2b3ab44abb51b8cad7543065d" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
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            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z4bb0be02911b4ac6b425e13b76a148c9" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

          <tr>
            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

      </table>
      <table cellspacing="0" cellpadding="0" id="z0ef0d8c0e6b045048c8dd52fc2e25558" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

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            <td style="width: 14.95pt;"><br>
            </td>
            <td style="width: 18.05pt; vertical-align: top;">&#8226;</td>
            <td style="width: auto; vertical-align: top;">
              <div>[***].</div>
            </td>
          </tr>

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      </div>
      <div style="text-align: center; font-weight: bold;"><u>Schedule 12.4</u></div>
      <div style="text-align: center;">&#160;</div>
      <div style="text-align: center; font-weight: bold;">Ionis Disclosure Schedule</div>
      <div><br>
      </div>
      <div>[***]</div>
    </div>
    <div> <br>
    </div>
    <div> <br>
    </div>
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<DOCUMENT>
<TYPE>EX-10.81
<SEQUENCE>14
<FILENAME>exhibit10-81.htm
<DESCRIPTION>EXHIBIT 10.81
<TEXT>
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  <div>
    <div style="text-align: right;">Exhibit 10.81</div>
    <div style="text-align: right;"> <br>
    </div>
    <div>
      <div style="text-align: right; font-style: italic;">Execution Version</div>
      <div style="text-align: right; font-style: italic;"> <br>
      </div>
    </div>
    <div>Certain portions of this exhibit, marked by [***], have been excluded because they are both not material and are the type that the registrant treats as private or confidential.</div>
    <div><br>
    </div>
    <div style="text-align: center; font-variant: small-caps;">Royalty Purchase Agreement</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">By and Between</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Ionis Pharmaceuticals, Inc.</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">and</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Akcea Therapeutics, Inc. (for the limited purposes set forth herein)</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">and</div>
    <div>&#160;</div>
    <div style="text-align: center; font-variant: small-caps;">Royalty Pharma Investments 2019 ICAV Dated as of January 9, 2023</div>
    <div>&#160;</div>
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    <!--PROfilePageNumberReset%LCR%1%-%-%-->
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      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;">Table of Contents</div>
      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;"> <br>
      </div>
      <div style="text-align: right; margin-right: 5.75pt; margin-left: 5.75pt;">Page</div>
    </div>
    <div> <br>
    </div>
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        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 1 DEFINED TERMS AND RULES OF CONSTRUCTION</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 1.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Definitions</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">1</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 1.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Certain Interpretations</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">13</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 1.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Headings</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 2 PURCHASE, SALE AND ASSIGNMENT OF THE ROYALTY</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 2.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Closing</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">14</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 2.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Assumed Obligations, Etc</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">16</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 2.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>True Sale</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">17</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 3 CLOSING</div>
          </td>
          <td style="width: 10%; vertical-align: top; text-align: right; background-color: rgb(204, 238, 255);" rowspan="1">17</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Closings; Payment of Purchase Price.</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">17</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Bill of Sale</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[Reserved]</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.4</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Escrow Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.5</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Form W-9</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.6</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Form W-8BEN</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.7</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Data Room</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 3.8</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Bilateral Common Interest Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 4 REPRESENTATIONS AND WARRANTIES</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 4.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Seller&#8217;s Representations and Warranties</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">18</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 4.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>The Buyer&#8217;s Representations and Warranties</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">29</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 4.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Implied Representations and Warranties</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">30</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 5 COVENANTS</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">30</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Disclosures</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">30</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Payments Received In Error</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">30</div>
          </td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Royalty Reduction</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">31</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.4</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Late Fee.</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">31</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.5</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Royalty Reports; Notices and Other Information from Licensee</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">31</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.6</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Notices and Other Information to Licensee</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">32</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.7</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Inspections and Audits of Licensee</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">33</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.8</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Amendment of License Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">33</td>
        </tr>

    </table>
    <div><br>
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      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;">Table of Contents</div>
      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;">(continued)</div>
      <div style="text-align: center;"> <br>
      </div>
      <div style="text-align: right; margin-right: 5.75pt; margin-left: 5.75pt;">Page</div>
      <div>&#160;</div>
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    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.9</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Maintenance of License Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">34</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.10</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Enforcement of License Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">36</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.11</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">37</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.12</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">38</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.13</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Preservation of Rights</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">38</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.14</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Enforcement; Defense; Prosecution and Maintenance</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">38</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.15</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Additional Monetizations</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">40</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.16</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Further Assurances</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">41</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.17</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Intercompany Relationship</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">41</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 5.18</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Tax Matters</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">42</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 6 CONFIDENTIALITY</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">42</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 6.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Confidentiality</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">42</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 6.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Authorized Disclosure</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">43</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 7 INDEMNIFICATION</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">44</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>General Indemnity</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">44</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Notice of Claims</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">45</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Limitations on Liability</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">45</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.4</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Third Party Claims</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">46</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.5</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exclusive Remedy</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 7.6</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Tax Treatment for Indemnification Payments</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 8 TERMINATION</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">47</div>
          </td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 8.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Mutual Termination</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 8.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Automatic Termination</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 8.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Survival</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">47</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1" colspan="3">
            <div>ARTICLE 9 MISCELLANEOUS</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">48</td>
        </tr>
        <tr>
          <td style="vertical-align: top;" rowspan="1" colspan="3">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.1</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Notices</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">48</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.2</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Expenses</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">49</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.3</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Assignment</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">49</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.4</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Amendment and Waiver</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">50</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.5</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Entire Agreement</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div style="text-align: right;">50</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">-ii-</font></div>
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    </div>
    <div>
      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;">Table of Contents</div>
      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;">(continued)</div>
      <div style="text-align: center; margin-right: 5.75pt; margin-left: 5.75pt;"> <br>
      </div>
      <div style="text-align: right; margin-right: 5.75pt; margin-left: 5.75pt;">Page</div>
      <div>&#160;</div>
    </div>
    <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.6</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>No Third Party Beneficiaries</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">50</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.7</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Governing Law</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">50</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.8</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>JURISDICTION; VENUE</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">51</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.9</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Severability</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">51</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.10</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Specific Performance</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">52</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.11</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Counterparts</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">52</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 12%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 72%; vertical-align: top;" rowspan="1">&#160;</td>
          <td style="width: 10%; vertical-align: top; text-align: right;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 6%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
          <td style="width: 12%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Section 9.12</div>
          </td>
          <td style="width: 72%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Relationships of the Parties.</div>
          </td>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255); text-align: right;">52</td>
        </tr>

    </table>
    <div>&#160;</div>
    <div style="font-weight: bold;"><u>Index of Exhibits</u></div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: rgb(0, 0, 0);" id="ze980922004054cc5ad43efe99f6c2b89">

        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">Exhibit A:</td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);" rowspan="1">Seller&#8217;s Wire Transfer Instructions</td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit B:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Form of Bill of Sale</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit C-1:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Form of Biogen Instruction Letter</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit C-2:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Form of Novartis Instruction Letter</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit D-1:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>2012 Biogen License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit D-2:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>2017 Biogen License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit D-3:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Novartis License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit D-4:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>UMass License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit D-5:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Cold Spring Harbor License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit D-6:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Intercompany License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit D-7:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Consent Letter</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit D-8:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Alnylam License</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit E:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Form of Escrow Agreement</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit F:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Form of Bilateral Common Interest Agreement</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit G:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Form of Biogen Trilateral Common Interest Agreement</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit H:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>Form of Novartis Trilateral Common Interest Agreement</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit I:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top;">
            <div>Exhibit J:</div>
          </td>
          <td style="width: 90%; vertical-align: top;">
            <div>[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Exhibit K:</div>
          </td>
          <td style="width: 90%; vertical-align: top; background-color: rgb(204, 238, 255);">
            <div>Revaluation Procedures</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div class="BRPFPageNumberArea" style="text-align: center;"><font class="BRPFPageNumber" style="font-size: 8pt; font-weight: normal; font-style: normal;">-iii-</font></div>
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    <!--PROfilePageNumberReset%Num%1%%%-->
    <div style="text-align: center;">ROYALTY PURCHASE AGREEMENT</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">This ROYALTY PURCHASE AGREEMENT, dated as of January 9, 2023 (this &#8220;<u>Agreement</u>&#8221;), is made and entered into by and between Ionis Pharmaceuticals, Inc., a Delaware corporation (the &#8220;<u>Seller</u>&#8221;) and, solely for
      the limited purposes set forth in Sections 2.1(a), 2.2, 2.3, 3.2, 3.4, 5.10(c) (the last sentence only), 5.14(b)(i), 5.14(b)(iii) and 9.3 hereunder,&#160; Akcea Therapeutics, Inc., a Delaware corporation (&#8220;<u>Akcea</u>&#8221;), on the one hand, and Royalty
      Pharma Investments 2019 ICAV, an Irish collective asset-management vehicle (the &#8220;<u>Buyer</u>&#8221;), on the other hand.&#160; Unless otherwise defined in this Agreement, capitalized terms have the meanings ascribed to them in Section 1 below.</div>
    <div>&#160;</div>
    <div style="text-align: center;"><u>W I T N E S S E T H</u>:</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">WHEREAS, pursuant to the 2012 Biogen License, the Seller has the right to receive, among other things, the Spinraza Royalty from Biogen based on 2012 Biogen License Net Sales of Spinraza;</div>
    <div>&#160;</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">WHEREAS, pursuant to the 2017 Biogen License, the Seller has the right to receive, among other things, the BIIB-115 Royalty from Biogen based on 2017 Biogen License Net Sales of BIIB-115;</div>
    <div>&#160;</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">WHEREAS, pursuant to the Novartis License, Akcea has the right to receive, among other things, the Pelacarsen Royalty from Novartis based on Novartis License Net Sales of Pelacarsen; and</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">WHEREAS, the Buyer desires to purchase the Purchased Royalty Payments from the Seller and Akcea, and the Seller and Akcea each desires to sell the Purchased Royalty Payments to the Buyer, in each case on the terms and
      conditions set forth herein.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">NOW THEREFORE, in consideration of the representations, warranties, covenants and agreements set forth herein and for good and valuable consideration, the receipt and adequacy of which are hereby acknowledged, the Seller
      and the Buyer hereby agree as follows:</div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 1</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">DEFINED TERMS AND RULES OF CONSTRUCTION</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 1.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Definitions</u>. As used in this Agreement, the following terms shall have the following meanings:</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2012 Biogen Historical License Correspondence</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2012 Biogen License</u>&#8221; means the Development, Option and License Agreement by and between Isis Pharmaceuticals, Inc. and Biogen Idec International Holding Ltd., dated January 3, 2012, as amended by that certain
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    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2012 Biogen Licensed Product</u>&#8221; has the meaning ascribed to the term &#8220;Product&#8221; in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">1</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
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    <div style="text-indent: 36pt;">&#8220;<u>2012 Biogen License Material Communications</u>&#8221; means copies of all written communications, other than 2012 Biogen Historical License Correspondence, between the Seller and Biogen involving the Spinraza Royalty or
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    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2012 Biogen License Net Sales</u>&#8221; has the meaning ascribed to the term &#8220;Net Sales&#8221; in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2017 Biogen Historical License Correspondence</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2017 Biogen License</u>&#8221; means the Research Collaboration, Option and License Agreement by and between Ionis Pharmaceuticals, Inc. and Biogen MA Inc., dated December 19, 2017.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2017 Biogen License Material Communications</u>&#8221; means copies of all written communications other than 2017 Biogen Historical License Correspondence, between Seller and Biogen involving the BIIB-115 Royalty or
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    <div>&#160;</div>
    <div style="text-indent: 36pt;"><font style="color: rgb(0, 0, 0);">&#8220;<u>2017 Biogen License Net Sales</u>&#8221; </font>has the meaning ascribed to the term &#8220;Net Sales&#8221; in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>2017 Biogen Licensed Product</u>&#8221; has the meaning ascribed to the term &#8220;Product&#8221; in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Additional Purchase Price Payment</u>&#8221; is defined in Section 2.1(b).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Adjusted Payment Period</u>&#8221; shall have the meaning ascribed to such term in Section 7.8.2(c) of the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Affiliate</u>&#8221; means, with respect to any particular Person, any other Person directly or indirectly, and whether by contract or otherwise, controlling, controlled by or under common control with such Person.&#160; For
      purposes of this definition, the word &#8220;control&#8221; (including, with correlative meaning, the terms &#8220;controlled by&#8221; or &#8220;under common control with&#8221;) means the actual power, either directly or indirectly through one or more intermediaries, to direct or
      cause the direction of the management and policies of such entity, whether by the ownership of at least fifty percent (50%) of the voting stock of such entity, or by contract or otherwise.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Agreed Amount</u>&#8221; is defined in Section 7.2(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Agreement</u>&#8221; is defined in the preamble. References to this Agreement include the Bill of Sale, the Disclosure Schedule, the Biogen Instruction Letter and the Novartis Instruction Letter.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Akcea</u>&#8221; is defined in the preamble.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Alnylam</u>&#8221; means Alnylam Pharmaceuticals, Inc.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
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    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Alnylam License</u>&#8221; means the Second Amended and Restated Strategic Collaboration and License Agreement between Alnylam and Seller, dated January 8, 2015, as amended by Amendment Number One on July 13, 2015 and as
      further amended, modified or otherwise supplemented from time to time in accordance with the terms hereof.</div>
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    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Bankruptcy Laws</u>&#8221; means, collectively, bankruptcy, insolvency, reorganization, moratorium, fraudulent conveyance, fraudulent transfer or other similar laws affecting the enforcement of
      creditors&#8217; rights generally.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115</u>&#8221; means the investigational antisense oligonucleotide in development as a medicine for spinal muscular atrophy known as BIIB-115 or previously known as ION306.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Know-How</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Know-How&#8221; under the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Licensed Patents</u>&#8221; is defined in Section 4.1(k)(i)(B).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Permitted Reduction</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Reversionary Rights</u>&#8221; is defined in Section 5.12(b)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Royalty</u>&#8221; means (A) any and all amounts owed, owing or otherwise payable to the Seller (i) under Section 6.6.1, 6.6.2(c) or 6.10 of the 2017 Biogen License with respect to 2017 Biogen License Net Sales of
      2017 Biogen Licensed Products, (ii) under Sections 7.5.5 or 7.6.1 of the 2017 Biogen License, and (iii) under Section 9.1 of the 2017 Biogen License, in the case of clauses (ii) and (iii) solely to the extent such payments relate to the amounts in
      clause (i) or 2017 Biogen License Net Sales of 2017 Biogen Licensed Products, (B) any and all Proceeds payable in lieu of such payments described in the foregoing clause (A), and (C) any and all interest payable to the Seller assessed on any payments
      described in the foregoing clauses (A) and (B), including under Section 6.12 of the 2017 Biogen License. For the avoidance of doubt, BIIB-115 Royalty shall not include any &#8220;Minimum Third Party Payments&#8221; (as defined in the 2017 Biogen License) after
      the expiration of the Reduced Royalty Period (as defined in the 2017 Biogen License).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>BIIB-115 Royalty Reports</u>&#8221; means the quarterly reports deliverable by Licensee pursuant to Section 6.9.1 of the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Bilateral Common Interest Agreement</u>&#8221; means a Common Interest Agreement among the Seller, Akcea, and the Buyer, in the form attached hereto as <u>Exhibit F</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Bill of Sale</u>&#8221; is defined in Section 3.2.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen</u>&#8221; means, collectively, Biogen Idec International Holding Ltd., Biogen MA Inc., and their respective Affiliates.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen BIIB-115 Patents</u>&#8221; means the patents owned or in-licensed by Biogen or its Affiliates that claim BIIB-115, including all patents the are listed at any time following the Closing Date in the Orange Book for
      BIIB-115.</div>
    <div>&#160;</div>
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      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen BIIB-115 Reversion Technology</u>&#8221; means all Biogen Technology (as defined in the 2017 Biogen License) Controlled by Biogen as of the date of reversion that covers or claims BIIB-115.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen Instruction Letter</u>&#8221; is defined in Section 5.5(g).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen Spinraza Patents</u>&#8221; means the patents owned or in-licensed by Biogen or its Affiliates that claim Spinraza, including all patents the are listed at any time following the Closing Date in the Orange Book for
      Spinraza.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen Spinraza Reversion Technology</u>&#8221; means all Biogen Idec Technology (as defined in the 2012 Biogen License) Controlled by Biogen as of the date of reversion that covers or claims Spinraza.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen Target</u>&#8221; means ribonucleic acid corresponding to the survival of motor neuron 2 (SMN2) gene.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Biogen Trilateral Common Interest Agreement</u>&#8221; means a Common Interest Agreement among the Seller, Biogen and the Buyer, in the form attached hereto as <u>Exhibit G</u>, or in such other form as may be mutually
      agreed by the Parties.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Business Day</u>&#8221; means any day other than (a) a Saturday or Sunday or (b) a day on which banking institutions located in New York are permitted or required by applicable law or regulation to remain closed.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Buyer</u>&#8221; is defined in the preamble.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Buyer Indemnified Parties</u>&#8221; is defined in Section 7.1(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Calendar Quarter</u>&#8221; means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Calendar Year</u>&#8221; means a period of twelve (12) consecutive months commencing on January 1 of the subject year.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Claim Amount</u>&#8221; is defined in Section 7.2(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Claim Notice</u>&#8221; is defined in Section 7.2(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Closing</u>&#8221; is defined in Section 3.1.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Closing Date</u>&#8221; means the date on which the Closing occurs.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Cold Spring Harbor</u>&#8221; means Cold Spring Harbor Laboratory.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Cold Spring Harbor License</u>&#8221; means the Amended and Restated Collaboration Agreement by and between Cold Spring Harbor and Seller, dated October 26, 2011, as amended and as further amended, modified or otherwise
      supplemented from time to time in accordance with the terms hereof.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">4</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Confidential Information</u>&#8221; is defined in Section 6.1.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Consensus Value</u>&#8221; means the net present value (applying an [***]% discount rate) of the projected net sales of the applicable Royalty Product using projections of Wall Street sell-side analysts then covering the
      Seller and the applicable Licensee, as determined in accordance with Exhibit K.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Consent Letter</u>&#8221; means that certain letter agreement by and between Seller and Akcea, dated as of January 16, 2017, as amended, modified or otherwise supplemented from time to time in accordance with the terms
      hereof.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Contract</u>&#8221; means any agreement, instrument, arrangement, modification, waiver or understanding, whether written or oral.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Controlled</u>&#8221; shall have the meaning ascribed to such term in the 2012 Biogen License, 2017 Biogen License, and Novartis License, as applicable to the applicable Licensee.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Data Room</u>&#8221; is defined in Section 3.7.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Disclosing Party</u>&#8221; is defined in Section 6.1.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Disclosure Schedule</u>&#8221; means the Disclosure Schedule, dated as of the date hereof, delivered to the Buyer by the Seller concurrently with the execution of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Enhanced Rights</u>&#8221; is defined in Section 5.15.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Escrow Account</u>&#8221; means the account controlled by the Escrow Agent pursuant to which each Licensee has been instructed to direct all amounts payable by it under the applicable License Agreement(s) in accordance
      with the Biogen Instruction Letter and Novartis Instruction Letter, as the case may be.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Escrow Agent</u>&#8221; means U.S. Bank National Association, or its permitted successor under the Escrow Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Escrow Agreement</u>&#8221; means the Escrow Agreement to be entered into among the Seller, the Buyer, and the Escrow Agent, substantially in the form attached hereto as <u>Exhibit E</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>FDA</u>&#8221; means the U.S. Food and Drug Administration, or a successor federal agency thereto in the United States.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>FDA Approval of Pelacarsen for [***]</u>&#8221; means receipt of NDA Approval of Pelacarsen to reduce the risk of [***] and elevated lipoprotein(a) (&#8220;<u>Lp(a)</u>&#8221;) (or any substantially similar indication for the
      reduction of cardiovascular event risk in adults with established cardiovascular disease and elevated Lp(a)).</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">5</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Governmental Entity</u>&#8221; means any: (a) nation, principality, republic, state, commonwealth, province, territory, county, municipality, district or other jurisdiction of any nature; (b) federal, state, local,
      municipal, foreign or other government; (c) governmental or quasi-governmental authority of any nature (including any governmental division, subdivision, department, agency, bureau, branch, office, commission, council, board, instrumentality,
      officer, official, representative, organization, unit, body or other entity and any court, arbitrator or other tribunal); (d) multi-national organization or body; or (e) individual, body or other entity exercising, or entitled to exercise, any
      executive, legislative, judicial, administrative, regulatory, police, military or taxing authority or power of any nature.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Indemnified Party</u>&#8221; is defined in Section 7.2(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Indemnifying Party</u>&#8221; is defined in Section 7.2(a).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Initial Payment Period</u>&#8221; shall have the meaning ascribed to such term in Section 7.8.2(a) of the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Initial Purchase Price</u>&#8221; means $500,000,000.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Intercompany License</u>&#8221; means that certain Development, Commercialization and License Agreement by and between Seller and Akcea, dated as of December 18, 2015, as amended, modified or otherwise supplemented from
      time to time in accordance with the terms hereof.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Ionis BIIB-115 Patents</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Patents&#8221; in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Ionis Core Technology Patents</u>&#8221; means Isis Core Technology Patents (as defined in the 2012 Biogen License), Isis Manufacturing and Analytical Patents (as defined in the 2012 Biogen License), Ionis Core Technology
      Patents (as defined in the 2017 Biogen License), Ionis Manufacturing and Analytical Patents (as defined in the 2017 Biogen License), and Akcea Core Technology Patents (as defined in the Novartis License) and Akcea Manufacturing and Analytical Patents
      (as defined in the Novartis License).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Ionis Pelacarsen Patents</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Patents&#8221; in the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Ionis Product-Specific Spinraza Patents</u>&#8221; has the meaning ascribed to the term &#8220;Isis Product-Specific Patents&#8221; in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Ionis Spinraza Patents</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Patents&#8221; in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Jointly-Owned BIIB-115 Program Patents</u>&#8221; has the meaning ascribed to the term &#8220;Jointly-Owned Program Patents&#8221; in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Jointly-Owned Pelacarsen Program Patents</u>&#8221; has the meaning ascribed to the term &#8220;Jointly-Owned Program Patents&#8221; in the Novartis License.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">6</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Jointly-Owned Spinraza Program Patents</u>&#8221; has the meaning ascribed to the term &#8220;Jointly-Owned Program Patents&#8221; in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Judgment</u>&#8221; means any judgment, order, writ, injunction, citation, award or decree of any nature.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Knowledge of the Seller</u>&#8221; means the actual knowledge of the Seller&#8217;s executive officers or other members of senior management with primary responsibility for the applicable subject matter.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>License Agreements</u>&#8221; means, collectively, the 2012 Biogen License, the 2017 Biogen License and the Novartis License (each, a &#8220;<u>License Agreement</u>&#8221;).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#160;&#8220;<u>License Correspondence</u>&#8221; means the 2012 Biogen Historical License Correspondence, the 2017 Biogen Historical License Correspondence, and the Novartis Historical License Correspondence.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Licensee</u>&#8221; or &#8220;<u>Licensees</u>&#8221; means, individually and collectively, Biogen and Novartis.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Lien</u>&#8221; means any mortgage, lien, pledge, assignment, license, sublicense, hypothec, charge, adverse claim, security interest, encumbrance or restriction of any kind, including any restriction on use, transfer or
      exercise of any other attribute of ownership of any kind (including, any agreement to give any of the foregoing, any conditional sale or other title retention agreement, and any lease in the nature thereof) and any option, trust or other preferential
      arrangement having the practical effect of any of the foregoing.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Loss</u>&#8221; means any and all Judgments, damages, losses, claims, costs, liabilities and expenses, including reasonable fees and out-of-pocket expenses of counsel.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Lp(a)</u>&#8221; is defined in the definition of &#8220;FDA Approval of Pelacarsen for [***]&#8221;.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Material Adverse Effect</u>&#8221; shall mean (i) a material adverse effect on the legality, validity or enforceability of any provision of this Agreement, (ii) a material adverse effect on the ability of the Seller to
      perform any of its obligations hereunder, (iii) a material adverse effect on the rights or remedies of the Buyer hereunder, (iv) a material adverse effect on the rights of the Seller under any of the License Agreements related to any Royalty or (v)
      an adverse effect in any material respect on the timing, amount or duration of any payments to be made to the Buyer in respect of the Royalty or the right of the Buyer to receive such payments (but excluding in each case any event, circumstance or
      change based on market conditions generally applicable to the industry in which the Seller operates or in any specific jurisdiction or geographical area, such as drug reimbursement rates or the commercial launch of a potentially competitive product).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Material Correspondence</u>&#8221; means any [***] that relates to a matter that would reasonably be expected to have a Material Adverse Effect.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>NDA</u>&#8221; means a New Drug Application submitted to the FDA in the United States in accordance with the Federal Food, Drug, and Cosmetic Act with respect to a pharmaceutical product.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">7</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>NDA Approval</u>&#8221; means, with respect to a product in the United States, FDA approval of an NDA sufficient for the manufacture, distribution, use, marketing and sale of such product in the United
      States.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>New BIIB-115 Arrangement</u>&#8221; is defined in Section 5.12(b)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>New Pelacarsen Arrangement</u>&#8221; is defined in Section 5.12(c)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>New SMA Compounds</u>&#8221; has the meaning ascribed to such term in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>New Spinraza Arrangement</u>&#8221; is defined in Section 5.12(a)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>NMA Compound</u>&#8221; has the meaning ascribed to such term in the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Non-Permitted Withholding Tax Reduction</u>&#8221; means any reduction to the Purchased Royalty Payments pursuant to Section 6.11.2 of the 2017 Biogen License [***], Section 6.11.2 of the 2012 Biogen License [***] or
      Section 7.13.3 of the Novartis License [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis</u>&#8221; means Novartis Pharma AG.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis Historical License Correspondence</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis Instruction Letter</u>&#8221; is defined in Section 5.5(g).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis License</u>&#8221; means the Strategic Collaboration, Option and License Agreement by and between Akcea, and Novartis, dated January 5, 2017, as amended by that certain Amendment No. 1 to the Strategic
      Collaboration, Option and License Agreement dated February 22, 2019.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis License Material Communications</u>&#8221; means copies of all written communications, other than Novartis Historical License Correspondence, between Akcea or Seller and Novartis involving the Pelacarsen Royalty
      or Pelacarsen and that would reasonably be expected to have a Material Adverse Effect related to the Pelacarsen Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis License Net Sales</u>&#8221; has the meaning ascribed to the term &#8220;Net Sales&#8221; in the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis Pelacarsen Patents</u>&#8221; means the patents owned or in-licensed by Novartis or its Affiliates that claim Pelacarsen, including all patents the are listed at any time following the Closing Date in the Orange
      Book for Pelacarsen.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis Pelacarsen Reversion Technology</u>&#8221; means all Novartis Background Technology (as defined in the Novartis License) Controlled by Novartis as of the date of such termination that covers or claims Pelacarsen
      as of such date.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Novartis Trilateral Common Interest Agreement</u>&#8221; means a Common Interest Agreement among Akcea, Novartis and the Buyer, in the form attached hereto as <u>Exhibit H</u>, or in such other form as may be mutually
      agreed by the Parties.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">8</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Patent Rights</u>&#8221; shall have the meaning ascribed to such term in the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Payment Triggering Event</u>&#8221; is defined in Section 2.1(b).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen</u>&#8221; has the meaning ascribed to the term &#8220;AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub>&#8221; in the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Commercial Launch</u>&#8221; means the first sale for use or consumption by an end-user of Pelacarsen in the United States after NDA Approval of Pelacarsen; provided however, that the following shall not trigger
      a Pelacarsen Commercial Launch: (a) any sale to an Affiliate of the Seller or any Licensee, (b) any use of Pelacarsen in clinical or non-clinical development activities, or (c) disposal or transfer of Pelacarsen for a <font style="font-style: italic;">bona fide</font> charitable purpose, compassionate use or samples.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Know-How</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Know-How&#8221; under the Novartis License.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Licensed Patents</u>&#8221; is defined in Section 4.1(k)(i)(C).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Permitted Reduction</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Reversionary Rights</u>&#8221; is defined in Section 5.12(c)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Royalty</u>&#8221; means (A) any and all amounts owed, owing or otherwise payable to Akcea (i) under Section 7.8.1, 7.8.2(c) and 7.12 of the Novartis License with respect to Novartis License Net Sales of
      Pelacarsen, (ii) under Section 8.6.4 of the Novartis License, and (iii) under Section 10.1 of the Novartis License, in the case of clauses (ii) and (iii) solely to the extent such payments relate to the amounts in the foregoing clause (i) or Novartis
      License Net Sales of Pelacarsen, (B) any and all Proceeds payable in lieu of such payments described in the foregoing clause (A), and (C) any and all interest payable to Akcea assessed on any payments described in the foregoing clauses (A) and (B),
      including under Section 7.14 of the Novartis License. For the avoidance of doubt, Pelacarsen Royalty shall not include any &#8220;Minimum Third Party Payments&#8221; (as defined in the Novartis License) after the expiration of the Adjusted Payment Period (as
      defined in the Novartis License).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Royalty Percentage</u>&#8221; means, as of any time of determination, with respect to (a) Buyer, (b) the Seller or (c) any other Person who has acquired an interest in or a Lien over any portion of the
      Pelacarsen Royalty as a result of a Seller Monetization Transaction, [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Royalty Reports</u>&#8221; means the quarterly reports deliverable by Licensee pursuant to Section 7.11.1 of the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen RP Control Shift</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">9</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Target</u>&#8221; means ribonucleic acid corresponding to the LPA (Lipoprotein(A)) gene.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Pelacarsen Upstream License</u>&#8221; means each of the Intercompany License, the Consent Letter, and the Alnylam License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Permitted Liens</u>&#8221; means any (a) mechanic&#8217;s, materialmen&#8217;s, and similar liens for amounts not yet due and payable, (b) statutory liens for taxes not yet due and payable or for taxes that the taxpayer is contesting
      in good faith, and (c) any liens created, permitted or required by this Agreement in favor of the Buyer or its Affiliates.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Permitted Reduction</u>&#8221; means a Spinraza Permitted Reduction (with respect to the Spinraza Royalty), BIIB-115 Permitted Reduction (with respect to the BIIB-115 Royalty), or Pelacarsen Permitted Reduction (with
      respect to the Pelacarsen Royalty); provided, however, a &#8220;Permitted Reduction&#8221; shall not include any amounts paid or payable by or on behalf of Seller to Cold Spring Harbor or UMass pursuant to the Upstream Licenses.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Person</u>&#8221; means any individual, firm, corporation, company, partnership, limited liability company, trust, joint venture, association, estate, trust, Governmental Entity or other entity, enterprise, association or
      organization.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Prime Rate</u>&#8221; means the prime rate published by the Wall Street Journal, from time to time, as the prime rate.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Proceeds</u>&#8221; means any amounts actually recovered by the Seller as a result of any settlement or resolution of any actions, suits, proceedings, claims or disputes.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Purchase Price</u>&#8221; means, collectively, the Initial Purchase Price and any Additional Purchase Price Payments.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Purchased Pelacarsen Royalty Payments</u>&#8221; means an amount equal to 25% of the Pelacarsen Royalty in respect of Novartis License Net Sales of Pelacarsen occurring from and after January 1, 2023.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Purchased Royalty Payments</u>&#8221; means, collectively, the Purchased SMA Royalty Payments and the Purchased Pelacarsen Royalty Payments.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Purchased SMA Royalty Payments</u>&#8221; means on a Calendar Year-by-Calendar Year basis, the applicable portion of the SMA Royalties with respect to SMA Combined Net Sales during such Calendar Year
      set forth in the table below, subject to the following limits: (i) during each Calendar Year, zero percent (0%) of the SMA Royalties related to SMA Combined Net Sales in excess of $1,500,000,000 during such Calendar Year; and (ii) zero percent (0%)
      of the SMA Royalties after the total amount of Purchased SMA Royalty Payments actually received by the Buyer hereunder equals the applicable SMA Royalty Cap.</div>
    <div><br>
    </div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z0fa364a5d18040118548c8287019e196">

        <tr>
          <td style="width: 50%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">Calendar Year</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center; color: rgb(0, 0, 0); font-weight: bold;">Applicable Portion of SMA Royalties</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2023</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">25%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2024</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">25%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2025</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">25%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2026</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">25%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2027</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center; color: rgb(0, 0, 0);">25%</div>
          </td>
        </tr>
        <tr>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">2028 and each Calendar Year thereafter</div>
          </td>
          <td style="width: 50%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; color: rgb(0, 0, 0);">45%</div>
          </td>
        </tr>

    </table>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">10</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="color: rgb(0, 0, 0);">In the event SMA Combined Net Sales exceed $1,500,000,000 during a subject Calendar Year, then the Purchased SMA Royalty Payments for the Calendar Quarter in which such $1,500,000,000 threshold is achieved shall be
      calculated on a pro rata basis based on the relative amounts of 2012 Biogen License Net Sales of Spinraza and 2017 Biogen License Net Sales of 2017 Biogen Licensed Products during such Calendar Quarter. By way of example only, if (a) SMA Combined Net
      Sales totaled $1,400,000,000 as of the nine-months ended September 30 of the subject Calendar Year and $1,650,000,000 as of the year-ended December 31 of the subject Calendar Year, and (b) of such $250,000,000 of SMA Combined Net Sales during the
      Calendar Quarter ended December 31, $200,000,000 was attributable to 2012 Biogen License Net Sales of Spinraza and $50,000,000 was attributable to 2017 Biogen License Net Sales of 2017 Biogen Licensed Products, then (x) of the $100,000,000 of SMA
      Combined Net Sales in the Calendar Quarter ending December 31 to be included in the calculation of the Purchased SMA Royalty Payments, $80,000,000 would be deemed attributable to 2012 Biogen License Net Sales of Spinraza and $20,000,000 would be
      deemed attributable to 2017 Biogen License Net Sales of 2017 Biogen Licensed Products and (y) $150,000,000 of SMA Combined Net Sales (comprised of $120,000,000 of 2012 Biogen License Net Sales of Spinraza and $30,000,000 of 2017 Biogen License Net
      Sales of 2017 Biogen Licensed Products) in the Calendar Quarter ending December 31 would be excluded from the calculation of Purchased SMA Royalty Payments.</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Receiving Party</u>&#8221; is defined in Section 6.1.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Representative</u>&#8221; means, with respect to any Person, (i) any direct or indirect stockholder, member or partner of such Person and (ii) any manager, director, officer, employee, agent, advisor or other
      representative (including attorneys, accountants, consultants, bankers, financial advisors and actual and potential lenders and investors) of such Person.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Royalty</u>&#8221; means, collectively, the Spinraza Royalty, the BIIB-115 Royalty, and the Pelacarsen Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Royalty Products</u>&#8221; means, collectively, Spinraza, BIIB-115, and Pelacarsen.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Royalty Reduction</u>&#8221; means any adjustment, counterclaim, reduction, credit, or deduction of, from or to any payment of a Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; color: rgb(0, 0, 0);">&#8220;<u>Royalty Reports</u>&#8221; means, collectively, the Spinraza Royalty Reports, BIIB-115 Royalty Reports, and Pelacarsen Royalty Reports.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Seller</u>&#8221; is defined in the preamble.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Seller Indemnified Parties</u>&#8221; is defined in Section 7.1(b).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Seller Monetization Transaction</u>&#8221; means, [***].</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">11</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Set-Off</u>&#8221; means any set-off or offset, by contract or under common law.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>SMA Combined Net Sales</u>&#8221; means the aggregate of 2012 Biogen License Net Sales of Spinraza and 2017 Biogen License Net Sales of 2017 Biogen Licensed Products.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>SMA Royalties</u>&#8221; means, collectively, the Spinraza Royalty and the BIIB-115 Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>SMA Royalty Cap</u>&#8221; means (i) if FDA Approval of Pelacarsen for [***] has occurred by the date that the total Purchased SMA Royalty Payments actually received by the Buyer hereunder equals $475,000,000, then
      $475,000,000 or (ii) otherwise, $550,000,000.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>SMA Royalty Percentage</u>&#8221; means, as of any time of determination, with respect to (a) Buyer, (b) the Seller or (c) any other Person who has acquired an interest in or a Lien over any portion of the Spinraza Royalty
      as a result of a Seller Monetization Transaction, [***].</div>
    <div><br>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>SMA RP Control Shift</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;s<u>NDA Approval</u>&#8221; means the FDA&#8217;s approval of a supplemental NDA, including all licenses and registrations,&#160; that are necessary for the sale and marketing of a pharmaceutical product in the United States.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza</u>&#8221; means nusinersen (or ISIS 396443).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Assigned Patents</u>&#8221; is defined in Section 4.1(k)(i)(A).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Know-How</u>&#8221; has the meaning ascribed to the term &#8220;Licensed Know-How&#8221; under the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Licensed Patents</u>&#8221; is defined in Section 4.1(k)(i)(A).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Permitted Reduction</u>&#8221; means [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Reversionary Rights</u>&#8221; is defined in Section 5.12(a)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Royalty</u>&#8221; means (A) any and all amounts owed, owing or otherwise payable to the Seller (i) under Section 6.6.1, 6.6.2(c) or 6.10 of the 2012 Biogen License with respect to 2012 Biogen License Net Sales of
      2012 Biogen Licensed Products, (ii) under Sections 7.5.5 or 7.6.1 of the 2012 Biogen License relating to a claim for infringement of the Spinraza Assigned Patents or Spinraza Licensed Patents, and (iii) under Section 9.1 of the 2012 Biogen License,
      in the case of clauses (ii) and (iii), solely to the extent such payments relate to the amounts in the foregoing clause (i) or 2012 Biogen License Net Sales of 2012 Biogen Licensed Products, (B) any and all Proceeds payable in lieu of such payments
      described in the foregoing clause (A), and (C) any and all interest payable to the Seller assessed on any payments described in the foregoing clauses (A) and (B), including under Section 6.12 of the 2012 Biogen License. For the avoidance of doubt,
      Spinraza Royalty shall not include &#8220;Minimum Third Party Payments&#8221; (as defined in the 2012 Biogen License) after the expiration of the Reduced Royalty Period (as defined in the 2012 Biogen License).</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">12</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza Royalty Reports</u>&#8221; means the quarterly reports deliverable by Licensee pursuant to Section 6.9.1 of the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Spinraza</u>&#160;<u>Upstream License</u>&#8221; means each of the UMass License and the Cold Spring Harbor License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Tax</u>&#8221; or &#8220;<u>Taxes</u>&#8221; means any federal, state, local or non-U.S. income, gross receipts, license, payroll, employment, excise, severance, occupation, premium, windfall profits, environmental, customs duties,
      capital stock, franchise, profits, withholding, social security, unemployment, disability, real property, personal property, abandoned property, value added, alternative or add-on minimum, estimated or other tax of any kind whatsoever, including any
      interest, penalty or addition thereto, whether disputed or not.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Third Party</u>&#8221; means any Person that is not the Buyer, an Affiliate of the Buyer, the Seller or an Affiliate of the Seller.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Triggering BIIB-115 Termination</u>&#8221; is defined in Section 5.12(b)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Triggering Pelacarsen Termination</u>&#8221; is defined in Section 5.12(c)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Triggering Spinraza Termination</u>&#8221; is defined in Section 5.12(a)(i).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>UCC</u>&#8221; means Article 9 of the New York Uniform Commercial Code, as in effect from time to time.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>UMass</u>&#8221; means University of Massachusetts.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>UMass License</u>&#8221; means the Exclusive License Agreement by and between UMass and Seller, dated January 14, 2010, as amended on November 28, 2011, and as further amended, modified or otherwise supplemented from time
      to time in accordance with the terms hereof.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">&#8220;<u>Upstream License</u>&#8221; means each Spinraza Upstream License and each Pelacarsen Upstream License.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 1.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Certain Interpretations</u>. Except where expressly stated otherwise in this Agreement, the following rules of interpretation apply to this Agreement: </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;either&#8221; and &#8220;or&#8221; are not exclusive and &#8220;include,&#8221; &#8220;includes&#8221; and &#8220;including&#8221; are not limiting and shall be deemed to be followed by the words &#8220;without limitation;&#8221;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;extent&#8221; in the phrase &#8220;to the extent&#8221; means the degree to which a subject or other thing extends, and such phrase does not mean simply &#8220;if;&#8221;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#8220;hereof,&#8221; &#8220;hereto,&#8221; &#8220;herein&#8221; and &#8220;hereunder&#8221; and words of similar import when used in this Agreement refer to this Agreement as a whole and not to any particular
      provision of this Agreement;</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">13</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;references to a Person are also to its permitted successors and assigns;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;definitions are applicable to the singular as well as the plural forms of such terms;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(f)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;unless otherwise indicated, references to an &#8220;Article&#8221;, &#8220;Section&#8221; or &#8220;Exhibit&#8221; refer to an Article or Section of, or an Exhibit to, this Agreement, and references to
      a &#8220;Schedule&#8221; refer to the corresponding part of the Disclosure Schedule;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(g)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;references to &#8220;$&#8221; or otherwise to dollar amounts refer to the lawful currency of the United States and all payments under this Agreement shall be made in immediately
      available funds;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(h)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;provisions referring to matters that would or could have, or would or could reasonably be expected to have, or similar phrases, shall be deemed to have such result
      or expectation with or without the giving of notice or the passage of time, or both;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;references to a law include any amendment or modification to such law and any rules and regulations issued thereunder, whether such amendment or modification is
      made, or issuance of such rules and regulations occurs, before or after the date of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(j)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;for covenants that are to be undertaken &#8220;reasonably,&#8221; such actions (or inactions) shall take into account Buyer&#8217;s economic interest in the Royalty and the impact of
      the applicable action (or inaction) on such interest.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 1.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Headings</u>. The table of contents and the descriptive headings of the several Articles and Sections of this Agreement and the Exhibits and Schedules are
      for convenience only, do not constitute a part of this Agreement and shall not control or affect, in any way, the meaning or interpretation of this Agreement. </div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 2<br>
      <br>
    </div>
    <div style="text-align: center;">PURCHASE, SALE AND ASSIGNMENT OF THE ROYALTY</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 2.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Closing</u><u>; Purchase Price</u>. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Upon the terms and subject to the conditions of this Agreement, at the Closing, the Seller shall, and shall cause Akcea to, and Akcea shall, sell, transfer, assign
      and convey to the Buyer, and the Buyer shall purchase, acquire and accept from the Seller, free and clear of all Liens, all of the Seller&#8217;s, or Akcea&#8217;s, as applicable, right, title and interest in and to the Purchased Royalty Payments. The purchase
      price to be paid at the Closing to the Seller for such sale, transfer, assignment and conveyance is the Initial Purchase Price. At the Closing, the Buyer shall pay the Seller the Initial Purchase Price by wire transfer to one or more accounts
      specified by the Seller on <u>Exhibit A</u>.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">14</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 76.5pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; Following the Closing, upon the occurrence of each of the following events (each a &#8220;<u>Payment Triggering Event</u>&#8221;), the Buyer shall make a cash payment (each an &#8220;<u>Additional



        Purchase Price Payment</u>&#8221;) to the Seller in the amount corresponding to such Payment Triggering Event:</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="2" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z2e31c16fd44b476a97a1dd0b52e8441f">

        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;"><u>#</u></div>
          </td>
          <td style="width: 75%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="font-weight: bold;"><u>PAYMENT TRIGGERING EVENT</u></div>
          </td>
          <td style="width: 20.04%; vertical-align: middle; border-left: #000000 2px solid; border-right: #000000 2px solid; border-top: #000000 2px solid; border-bottom: #000000 2px solid;">
            <div style="text-align: center; font-weight: bold;"><u>ADDITIONAL</u></div>
            <div style="text-align: center; font-weight: bold;"><u> PURCHASE </u></div>
            <div style="text-align: center; font-weight: bold;"><u>PRICE </u></div>
            <div style="text-align: center; font-weight: bold;"><u>PAYMENT</u></div>
            <div style="text-align: center; font-weight: bold;"><u> AMOUNT</u></div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">1.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">2.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">3.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">4.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">5.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">6.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: middle; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-indent: -18pt; margin-left: 22.5pt;">7.</div>
          </td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div>[***]</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0); background-color: rgb(204, 238, 255);">
            <div style="text-align: center;">[***]</div>
          </td>
        </tr>
        <tr>
          <td style="width: 5%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">&#160;</td>
          <td style="width: 75%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="font-weight: bold; text-align: right;">TOTAL</div>
          </td>
          <td style="width: 20.04%; vertical-align: top; border-width: 2px; border-style: solid; border-color: rgb(0, 0, 0);">
            <div style="text-align: center; font-weight: bold;">$625,000,000</div>
          </td>
        </tr>

    </table>
    <div> <br>
    </div>
    <div>Notwithstanding the foregoing, if each of Payment Triggering Events #2 through #7 above are achieved, then the Payment Triggering Event in #1 above, if not previously triggered, will be deemed to be achieved as well and the Buyer shall make the
      Additional Purchase Price Payment to the Seller in the amount corresponding to such Payment Triggering Event in accordance with Section 2.1(d) below.</div>
    <div>&#160;</div>
    <div>For clarity, (i) only one Additional Purchase Price Payment shall be due hereunder with respect to each Payment Triggering Event and no Additional Purchase Price Payment shall be payable for repeated achievements of any such Payment Triggering
      Events; provided that for the avoidance of doubt, more than one Payment Triggering Event may be achieved for any particular Calendar Year, and (ii) [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Each party hereto hereby agrees and acknowledges that: (i) the Additional Purchase Price Payments are contingent payment obligations of the Buyer and there can be no
      assurance regarding the occurrence of any of the Payment Triggering Events and (ii) the Buyer shall have no obligation or liability with respect to any Additional Purchase Price Payment unless and until the corresponding Payment Triggering Event has
      occurred.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Seller shall notify the Buyer promptly following the achievement of any Payment Triggering Event, and the Buyer shall pay the corresponding Additional Purchase
      Price Payment to the Seller within [***] Business Days following such notice (except in the case of Payment Triggering Event #5, which shall be paid within [***] Business Days of the date of [***].</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">15</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Each party hereto further agrees and acknowledges that the other party shall have the right to offset any Agreed Amounts or Losses resolved pursuant to a final and
      unappealable ruling in accordance with the provisions of Section 9.8 owed by such party to the other party hereunder. In addition, in the event that a court of competent jurisdiction makes a final and unappealable ruling in accordance with the
      provisions of Section 9.8 that the Buyer has breached this Agreement by failing to pay any Additional Purchase Price Payment when due, the Seller shall have a right to recoup such Additional Purchase Price Payment not paid by Buyer, together with any
      late fee in respect thereof in accordance with Section 5.4, from the Purchased Royalty Payments. For the avoidance of doubt, this Agreement (including all agreements, schedules and exhibits hereto and the documents and instruments referred to herein
      that are to be delivered at the Closing Date) shall constitute a &#8220;single integrated agreement&#8221; and the transactions contemplated thereby shall constitute a &#8220;single integrated transaction&#8221; in each case for purposes of recoupment.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(f)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Subject to Section 2.1(e), any Additional Purchase Price Payment owed to the Seller by the Buyer in accordance with Section 2.1(b) shall be paid to the Seller by
      wire transfer to the account(s) specified by the Seller on <u>Exhibit A</u> (or such other account(s) as specified by the Seller in a writing delivered to the Buyer in accordance with Section 9.1). The parties hereto further agree that: (i) the
      aggregate Additional Purchase Price Payments payable by the Buyer hereunder shall not exceed $625,000,000 and (ii) the total Purchase Price payable to the Seller by the Buyer hereunder (inclusive of the Initial Purchase Price and, if required to be
      paid under this Agreement, all of the Additional Purchase Price Payments) shall in no event exceed $1,125,000,000 in the aggregate.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 2.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Assumed Obligations, Etc</u><u>.</u> Notwithstanding any provision in this Agreement to the contrary, the Buyer is purchasing, acquiring and accepting
      only the Purchased Royalty Payments, and is not assuming any liability or obligation of the Seller or Akcea of whatever nature, whether presently in existence or arising or asserted hereafter, under the License Agreements or otherwise. Except as
      specifically set forth herein in respect of the Purchased Royalty Payments purchased, acquired and accepted hereunder, the Buyer does not, by such purchase, acquisition and acceptance, acquire any other contract rights of the Seller or Akcea under
      the License Agreements or otherwise or any other assets of the Seller or Akcea. </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">16</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 2.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>True Sale</u>. It is the intention of the parties hereto that the sale, transfer, assignment and conveyance contemplated by this Agreement be, and is, a
      true, complete, absolute and irrevocable sale, transfer, assignment and conveyance by the Seller and Akcea to the Buyer of all of the Seller&#8217;s, and Akcea&#8217;s (as applicable) rights, title and interests in and to the Purchased Royalty Payments and the
      Seller relinquishes all title and control over the Purchased Royalty Payments upon such sale, transfer, assignment and conveyance. None of the Seller, Akcea or the Buyer intends the transactions contemplated by this Agreement to be, or for any
      purpose characterized as, a loan from the Buyer to the Seller or Akcea (as applicable) or to any of the Seller&#8217;s or Akcea&#8217;s Affiliates, or a pledge, a security interest, a financing transaction or a borrowing. It is the intention of the parties
      hereto that the beneficial interest in and title to the Purchased Royalty Payments and any &#8220;proceeds&#8221; (as defined in the UCC) thereof shall not be part of the Seller&#8217;s or Akcea&#8217;s estates in the event of the filing of a petition by or against the
      Seller under any Bankruptcy Laws.&#160; Each of the Seller, Akcea and the Buyer hereby waives, to the maximum extent permitted by applicable law, any right to contest or otherwise assert that the sale contemplated by this Agreement does not constitute a
      true, complete, absolute and irrevocable sale, transfer, assignment and conveyance by the Seller and Akcea to the Buyer of all of the Seller&#8217;s and Akcea&#8217;s right, title and interest in and to the Purchased Royalty Payments under applicable law, which
      waiver shall, to the maximum extent permitted by applicable law, be enforceable against the Seller or Akcea (as applicable) in any bankruptcy or insolvency proceeding relating to the Seller or Akcea or either of their subsidiaries. Accordingly, the
      Seller and Akcea shall treat the sale, transfer, assignment and conveyance of the Purchased Royalty Payments as a sale of an &#8220;account&#8221; or a &#8220;payment intangible&#8221; (as appropriate) in accordance with the UCC, and the Seller and Akcea each hereby
      authorizes the Buyer to file financing statements (and continuation statements with respect to such financing statements when applicable) naming the Seller and Akcea (as applicable) as the debtor and the Buyer as the secured party in respect of the
      Purchased Royalty Payments. Not in derogation of the foregoing statement of the intent of the parties hereto in this regard, and for the purposes of providing additional assurance to the Buyer in the event that, despite the intent of the parties
      hereto, the sale, transfer, assignment and conveyance contemplated hereby is hereafter held not to be a sale, each of the Seller and Akcea does hereby grant to the Buyer a security interest in and to all right, title and interest of the Seller or
      Akcea (as applicable), in, to and under the Purchased Royalty Payments and any &#8220;proceeds&#8221; (as defined in the UCC) thereof as security for all of the Seller&#8217;s and Akcea&#8217;s obligations hereunder, including the payment of the Purchased Royalty Payments,
      and each of the Seller and Akcea does hereby authorize the Buyer, from and after the Closing, to file such financing statements (and continuation statements with respect to such financing statements when applicable) in such manner and such
      jurisdictions as are necessary or appropriate to perfect such security interest.&#160; At such time as the Buyer receives zero percent (0%) of the SMA Royalties after the total amount of Purchased SMA Royalty Payments actually received by the Buyer
      hereunder equals the applicable SMA Royalty Cap, the security interest granted pursuant to the immediately preceding sentence as it relates to the Purchased SMA Royalty Payments shall be released and the Buyer shall, at the request and sole expense
      of the Seller, execute and deliver to the Seller all releases and other documents reasonably necessary or advisable for the release of the Liens against the Purchased SMA Royalty Payments, including the filing of amendments to any UCC financing
      statements against the Seller to evidence such termination. </div>
    <div><br>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 3</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">CLOSING</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Closings; Payment of Purchase Price</u>.The purchase and sale of the Purchased Royalty Payments shall take place remotely via the exchange of documents
      and signatures on the date hereof or such other place, time and date as the parties hereto may mutually agree (the &#8220;<u>Closing</u>&#8221;). At the Closing, the Buyer shall deliver (or cause to be delivered) payment of the Initial Purchase Price to the
      Seller by wire transfer to one or more accounts specified by the Seller on <u>Exhibit A</u>. </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">17</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Bill of Sale</u>. At the Closing, upon confirmation of the receipt of the Initial Purchase Price, the Seller and Akcea shall deliver to the Buyer a duly
        executed bill of sale evidencing the sale, transfer, assignment and conveyance of the Purchased Royalty Payments, substantially in the form attached hereto as <u>Exhibit B</u> (the &#8220;<u>Bill of Sale</u>&#8221;). </div>
    </div>
  </div>
  <div><font style="color: rgb(1, 0, 0);"> <br>
    </font>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>[Reserved]</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.4</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Escrow Agreement</u>. Within [***] Business Days following the Closing, the Buyer, the Seller and Akcea shall execute and deliver the Escrow Agreement to
      the Escrow Agent. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.5</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Form W-9</u>. At the Closing, the Seller shall deliver to the Buyer a valid, properly executed IRS Form W-9 certifying that the Seller is exempt from U.S.
      federal withholding tax and &#8220;backup&#8221; withholding tax. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.6</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Form W-8BEN</u><u>-E</u>. At the Closing, the Buyer shall deliver to the Seller a valid, properly executed IRS Form W-8BEN-E certifying that the Buyer is
      exempt from U.S. federal withholding tax with respect to any and all Purchased Royalty Payments. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.7</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Data Room</u>. The Seller shall have delivered to the Buyer an electronic copy of all of the information and documents posted to the virtual data room
      established by the Seller as of the date hereof and made available to the Buyer via Firmex (the &#8220;<u>Data Room</u>&#8221;) for archival purposes only. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 3.8</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Bilateral Common Interest Agreement</u>. At the Closing each of the Seller and the Buyer shall execute and deliver to the other party hereto the Bilateral
      Common Interest Agreement. </div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 4<br>
      <br>
    </div>
    <div style="text-align: center;">REPRESENTATIONS AND WARRANTIES</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 4.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Seller&#8217;s Representations and Warranties</u>. Except as set forth in the Disclosure Schedule, the Seller represents and warrants to the Buyer that as of
      the Closing Date: </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Existence; Good Standing</u>. Each of Akcea and the Seller is a corporation duly incorporated, validly existing and in good standing under the laws of Delaware.
      Each of Akcea and the Seller is duly licensed or qualified to do business and is in corporate good standing in each jurisdiction in which the nature of the business conducted by it or the character or location of the properties and assets owned,
      leased or operated by it makes such licensing or qualification necessary, except where the failure to be so licensed or qualified and in corporate good standing has not and would not reasonably be expected to have, either individually or in the
      aggregate, a Material Adverse Effect. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Authorization</u>. Each of the Seller and Akcea has all requisite corporate power and authority to execute, deliver and perform its obligations under this
      Agreement. The execution, delivery and performance of this Agreement, and the consummation of the transactions contemplated hereby, have been duly authorized by all necessary corporate action on the part of each of the Seller and Akcea. </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">18</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Enforceability</u>. The Agreement has been duly executed and delivered and constitutes a valid and binding obligation of each of the Seller and Akcea enforceable
      against the Seller and Akcea in accordance with its terms, except as such enforceability may be limited by applicable Bankruptcy Laws or general principles of equity (whether considered in a proceeding in equity or at law). </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Conflicts</u>. The execution, delivery and performance by the Seller or Akcea of this Agreement and the consummation of the transactions contemplated hereby do
      not and shall not (i) contravene or conflict with the organizational documents of the Seller or Akcea, (ii) contravene or conflict with or constitute a material default under any law or Judgment binding upon or applicable to the Seller or Akcea,
      (iii) contravene or conflict with or constitute a default under any of the License Agreements or under any of the Upstream Licenses or (iv) contravene or conflict with or constitute a default under any other material contract or material agreement
      binding upon or applicable to the Seller or Akcea. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Consents</u>. Except for filings required by the federal securities laws or stock exchange rules, no consent, approval, license, order, authorization,
      registration, declaration or filing with or of any Governmental Entity or other Person is required to be done or obtained by the Seller in connection with (i) the execution and delivery by the Seller of this Agreement, (ii) the performance by the
      Seller of its obligations under this Agreement or (iii) the consummation by the Seller of any of the transactions contemplated by this Agreement. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(f)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Litigation</u>. There is no action, suit, claim, investigation or proceeding pending or, to the Knowledge of the Seller, threatened, including before any
      Governmental Entity, against or involving the Seller or any of its Affiliates, or any of their respective properties or assets that, individually or in the aggregate, would be reasonably be expected to result in a Material Adverse Effect or which
      questions the validity of this Agreement or the transactions contemplated hereby or any action taken or to be taken pursuant hereto. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(g)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Compliance with Laws</u>. Neither the Seller nor any of its Affiliates is in violation of, and to the Knowledge of the Seller, neither the Seller nor any of its
      Affiliates is under investigation with respect to nor has the Seller or any of its Affiliates been threatened in writing to be charged with or given written notice of any violation of, any law or Judgment applicable to the Seller or any of its
      Affiliates, which violation would reasonably be expected to have, either individually or in the aggregate, a Material Adverse Effect. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(h)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[<u>Reserved</u>.]</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>License Agreement</u>s. Attached hereto as <u>Exhibit D-1</u>, <u>D-2</u>, <u>D-3</u>, <u>D-4</u>, <u>D-5</u>, <u>D-6</u>&#160;<u>D-7</u>, and<u> D-8</u> is a
      true, correct and complete copy of the 2012 Biogen License, 2017 Biogen License, Novartis License, the UMass License, the Cold Spring Harbor License, the Intercompany License, the Consent Letter, and the Alnylam License respectively. The Seller has
      delivered to the Buyer via the Data Room true, correct and complete copies of all License Correspondence. </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">19</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Other Agreements</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(A)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except for the 2017 Biogen License, and except as set forth on <u>Schedule 4.1(i)(i)(A)</u> of the Disclosure Schedule, the 2012 Biogen License
      is the only Contract between the Seller (or any predecessor or Affiliate thereof), on the one hand, and Biogen (or any predecessor or Affiliate thereof), on the other hand, relating to Spinraza or the Biogen Target, and there are no other Contracts
      (other than the 2017 Biogen Agreement) between the Seller (or any predecessor or any Affiliate thereof), on the one hand, and any other Person, including Biogen (or any predecessor or Affiliate thereof), on the other hand, that relate to the 2012
      Biogen License, any Spinraza Licensed Patent (other than an Ionis Core Technology Patent), the 2012 Biogen Licensed Product (including the development or commercialization thereof), Spinraza or the Spinraza Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(B)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except for the 2012 Biogen License, and except as set forth on <u>Schedule 4.1(i)(i)(B)</u> of the Disclosure Schedule, the 2017 Biogen License
      is the only Contract between the Seller (or any predecessor or Affiliate thereof), on the one hand, and Biogen (or any predecessor or Affiliate thereof), on the other hand, relating to BIIB-115 or the Biogen Target, and there are no other Contracts
      between the Seller (or any predecessor or any Affiliate thereof), on the one hand, and any other Person, including Biogen (or any predecessor or Affiliate thereof), on the other hand, that relate to the 2017 Biogen License, any BIIB-115 Licensed
      Patent&#160; (other than an Ionis Core Technology Patent), the 2017 Biogen Licensed Product (including the development or commercialization thereof), BIIB-115 or the BIIB-115 Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(C)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth on <u>Schedule 4.1(i)(i)(C)</u> of the Disclosure Schedule, the Novartis License is the only Contract between the Seller (or
      any predecessor or Affiliate thereof), on the one hand, and Novartis (or any predecessor or Affiliate thereof), on the other hand, relating to Pelacarsen or the Pelacarsen Target, and there are no other Contracts between the Seller (or any
      predecessor or any Affiliate thereof), on the one hand, and any other Person, including Novartis (or any predecessor or Affiliate thereof), on the other hand, that relate to the Novartis License, any Pelacarsen Licensed Patent (other than any Ionis
      Core Technology Patent), Pelacarsen (including the development or commercialization thereof), or the Pelacarsen Royalty.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(D)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth on <u>Schedule 4.1(i)(i)(D)</u> of the Disclosure Schedule, UMass License is the only Contract between the Seller (or any
      predecessor or Affiliate thereof), on the one hand, and UMass (or any predecessor or Affiliate thereof), on the other hand, relating to the subject matter thereof, and there are no other Contracts between the Seller (or any predecessor or any
      Affiliate thereof), on the one hand, and any other Person, including UMass (or any predecessor or Affiliate thereof), on the other hand, that relate to the Spinraza Licensed Patents owned by UMass.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">20</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(E)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth on <u>Schedule 4.1(i)(i)(E)</u> of the Disclosure Schedule, the Cold Spring Harbor License is the only Contract between the
      Seller (or any predecessor or Affiliate thereof), on the one hand, and Cold Spring Harbor (or any predecessor or Affiliate thereof), on the other hand, relating to the subject matter thereof, and there are no other Contracts between the Seller (or
      any predecessor or any Affiliate thereof), on the one hand, and any other Person, including Cold Spring Harbor (or any predecessor or Affiliate thereof), on the other hand, that relate to the Spinraza Licensed Patents owned by Cold Spring Harbor.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(F)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth on <u>Schedule 4.1(i)(i)(F)</u> of the Disclosure Schedule, the Intercompany License and Consent Letter are the only
      Contracts between the Seller (or any predecessor or Affiliate thereof), on the one hand, and Akcea (or any predecessor or Affiliate thereof), on the other hand, relating to the subject matter thereof, and there are no other Contracts between the
      Seller (or any predecessor or any Affiliate thereof), on the one hand, and any other Person, including Akcea (or any predecessor or Affiliate thereof), on the other hand, that relate to the Pelacarsen Licensed Patents owned by Seller.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(G)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth on <u>Schedule 4.1(i)(i)(G)</u> of the Disclosure Schedule, the Alnylam License is the only Contract between the Seller (or
      any predecessor or Affiliate thereof), on the one hand, and Alnylam (or any predecessor or Affiliate thereof), on the other hand, relating to the subject matter thereof, and there are no other Contracts between the Seller (or any predecessor or any
      Affiliate thereof), on the one hand, and any other Person, including Alnylam (or any predecessor or Affiliate thereof), on the other hand, that relate to the Pelacarsen Licensed Patents owned by Alnylam.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(H)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; There is no proposal to amend, modify or waive any provision of any License Agreement or any Upstream License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Licenses/Sublicenses</u>. Except as set forth on <u>Schedule 4.1(i)(ii)</u> of the Disclosure Schedule, to the Knowledge of the Seller, there
      are no licenses or sublicenses entered into by Biogen or Novartis in respect of such Licensee&#8217;s rights and obligations under any License Agreement. The Seller has not received any notice from Biogen pursuant to Section 4.1.2 of the 2012 Biogen
      License or Section 4.1.2 of the 2017 Biogen License.&#160; Akcea has not received any updates at JDCC (as defined in the Novartis License) meetings regarding licenses or sublicenses in respect of Novartis&#8217; rights and obligations under any License
      Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Validity and Enforceability of License Agreements and Upstream Licenses; No Breaches or Defaults; No Repudiation</u>. Each License Agreement
      and each Upstream License is legal, valid, binding, enforceable, and in full force and effect, except as such enforceability may be limited by applicable Bankruptcy Laws or general principles of equity (whether considered in a proceeding in equity or
      at law). Neither the Seller, Akcea nor, to the Knowledge of the Seller, no other party to any License Agreement or any Upstream License is, or has at any time been in material breach thereof or default thereunder, and to the Knowledge of the Seller,
      no event has occurred that with notice or lapse of time would constitute such a material breach, or permit termination, modification, or acceleration, under the License Agreement. Neither the Seller nor Akcea has received any written notice in
      connection with any License Agreement or any Upstream License challenging the validity or enforceability of any provision of such agreement, including the obligation to pay any portion of the Royalty without Set-Off or any Royalty Reduction, and
      neither the Seller nor Akcea has received any written notice in connection with any License Agreement or Upstream License challenging the interpretation of any provision of such agreement, except in respect of any Upstream License as would not
      reasonably be expected to have a Material Adverse Effect.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">21</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Products</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(A)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Spinraza is a 2012 Biogen Licensed Product under the 2012 Biogen License and, to the Knowledge of the Seller, there are no other 2012 Biogen
      Licensed Products being researched, developed or commercialized by or on behalf of Biogen under the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(B)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; BIIB-115 is a 2017 Biogen Licensed Product and an NMA Compound under the 2017 Biogen License and, to the Knowledge of the Seller, there are no
      other 2017 Biogen Licensed Products being researched, developed or commercialized by or on behalf of Biogen under the 2017 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(C)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx</sub> (as defined in the Novartis License), includes the
      investigational antisense oligonucleotide medicine known as Pelacarsen, which is designed to reduce apolipoprotein(a) in the liver. To the Knowledge of the Seller, other than such investigational antisense oligonucleotide medicine, there are no other
      AKCEA-APO(a)-L<sub style="vertical-align: bottom; line-height: 1; font-size: smaller;">Rx </sub> products (as defined in the Novartis License) being researched, developed or commercialized by or on behalf of Novartis under the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(v)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Liens or Assignments by the Seller</u>. Neither Seller nor Akcea has, except for Permitted Liens and as contemplated hereby, conveyed,
      assigned or in any other way transferred or granted any Liens (other than sublicenses under any License Agreement or any Upstream License) upon or with respect to all or any portion of its right, title and interest in and to any Royalty, any License
      Agreement, or any Upstream License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(vi)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Waivers or Releases</u>. Neither the Seller nor Akcea has granted any material waiver under any License Agreement or any Upstream License
      and has not released Biogen, Novartis, UMass, Cold Spring Harbor, Alnylam, Akcea, or Seller, in whole or in part, from any of its material obligations under any License Agreement or any Upstream License.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">22</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(vii)</font>&#160;&#160;&#160;&#160;&#160;&#160; <u>No Termination</u>. The Seller has not (A) (1) given Biogen any notice of termination of the 2012 Biogen License or the 2017 Biogen License
      (whether in whole or in part) or any notice expressing any intention to terminate the 2012 Biogen License or 2017 Biogen License, (2) given Novartis any notice of termination of the Novartis License (whether in whole or in part) or any notice
      expressing any intention to terminate the Novartis License, (3) given UMass any notice of termination of the UMass License (whether in whole or in part) or any notice expressing any intention to terminate the UMass License, (4) given Cold Spring
      Harbor any notice of termination of the Cold Spring Harbor License (whether in whole or in part) or any notice expressing any intention to terminate the Cold Spring Harbor License, (5) given Akcea any notice of termination of any Intercompany License
      or Consent Letter (whether in whole or in part) or any notice expressing any intention to terminate the Intercompany License or Consent Letter, (6) given Alnylam any notice of termination of the Alnylam License (whether in whole or in part) or any
      notice expressing any intention to terminate the Alnylam License, or (B) received any notice of termination of any License Agreement or Upstream License (whether in whole or in part) or any notice expressing any intention to terminate any License
      Agreement or Upstream License. To the Knowledge of the Seller, no event has occurred that would give rise to the expiration or termination of, or any party having the right to terminate for breach, any License Agreement or Upstream License except in
      respect of any Upstream License as would not reasonably be expected to have a Material Adverse Effect.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(viii)</font>&#160;&#160;&#160;&#160;&#160; <u>Payments Made</u>. The Seller has timely received from Biogen the full amount of the payments due and payable under the 2012 Biogen License and
      2017 Biogen License. The Seller has timely received from Novartis the full amount of the payments due and payable under the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ix)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Assignments by Licensee</u>. The Seller has not consented to any assignment, delegation or other transfer by Biogen or any of its
      predecessors of any of their rights or obligations under the 2012 Biogen License or 2017 Biogen License, and, to the Knowledge of the Seller, Biogen has not assigned or otherwise transferred any of its rights or obligations under the 2012 Biogen
      License or 2017 Biogen License. The Seller has not consented to any assignment, delegation or other transfer by Novartis or any of its predecessors of any of their rights or obligations under the Novartis License, and, to the Knowledge of the Seller,
      Novartis has not assigned or otherwise transferred any of its rights or obligations under the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(x)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Indemnification Claims</u>. The Seller has not (A) notified Biogen or any other Person of any claims for indemnification under the 2012
      Biogen License or 2017 Biogen License, (B) notified Novartis or any other Person of any claims for indemnification under the Novartis License, or (C) received any claims for indemnification under any License Agreement.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">23</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(xi)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>No Royalty Reductions</u>.</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt; text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(A)</font>&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, the amount of the Spinraza Royalty due and payable under Section 6.6.1 of the 2012 Biogen License is not currently
      subject to any Royalty Reduction (including any Spinraza Permitted Reduction). To<font style="font-weight: bold;">&#160;</font>the Knowledge of the Seller, no event or condition exists that, upon notice or passage of time or both, would reasonably be
      expected to permit Biogen to claim, or have the right to claim, a Royalty Reduction (including any Spinraza Permitted Reduction) against the Spinraza Royalty (other than as contemplated by Section 6.6.2(c) of the 2012 Biogen License).</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt; text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(B)</font>&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, the amount of the BIIB-115 Royalty due and payable under Section 6.6.1 of the 2017 Biogen License is not currently
      subject to any Royalty Reduction (including any BIIB-115 Permitted Reduction). To<font style="font-weight: bold;">&#160;</font>the Knowledge of the Seller, no event or condition exists that, upon notice or passage of time or both, would reasonably be
      expected to permit Biogen to claim, or have the right to claim, a Royalty Reduction (including any BIIB-115 Permitted Reduction) against the BIIB-115 Royalty (other than as contemplated by Section 6.6.2(c) of the 2017 Biogen License).</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt; text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(C)</font>&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, the amount of the Pelacarsen Royalty due and payable under Section 7.8.1 of the Novartis License is not currently
      subject to any Royalty Reduction (including any Pelacarsen Permitted Reduction). To<font style="font-weight: bold;">&#160;</font>the Knowledge of the Seller, no event or condition exists that, upon notice or passage of time or both, would reasonably be
      expected to permit Novartis to claim, or have the right to claim, a Royalty Reduction (including any Pelacarsen Permitted Reduction) against the Pelacarsen Royalty (other than as contemplated by Section 7.6.2(c) of the Novartis License).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(xii)</font>&#160;&#160;&#160;&#160;&#160;&#160; <u>No Notice of Infringement</u>. The Seller has not received any written notice from, or given any written notice to, (A) Biogen pursuant to
      Section 7.5.1 of the 2012 Biogen License or Section 7.5.1 of the 2017 Biogen License, (B) Novartis pursuant to Section 8.6.1 of the Novartis License, (C) UMass pursuant to Section 6.4(a) of the UMass License, (D) Cold Spring Harbor pursuant to
      Section&#160; 5.4 of the Cold Spring Harbor License, (E) Akcea pursuant to Section 9.3.1 of the Intercompany License, or (F) Alnylam pursuant to Section 11.5 of the Alnylam License.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(xiii)</font>&#160;&#160;&#160;&#160;&#160; <u>Audits</u>.<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">&#160;</sup> Except as set forth on <u>Schedule 4.1(i)(xiii)</u>
      of the Disclosure Schedule, the Seller has not initiated, pursuant to Section 6.10 of the 2012 Biogen License, Section 6.10 of the 2017 Biogen License, or Section 7.12 of the Novartis License or otherwise any inspection or audit of books of accounts
      or other records of Biogen or Novartis, or the calculation of royalties or other amounts payable to the Seller under any License Agreement.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">24</font></div>
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    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(xiv)</font>&#160;&#160;&#160;&#160;&#160; <u>Additional Rights</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 67.5pt; margin-left: 76.5pt;"><font style="color: rgb(1, 0, 0);">(A)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Biogen has not exercised the Diagnostic Option (as defined in the 2012 Biogen License) pursuant to Section 3.2.1 of the 2012 Biogen License.&#160;
      Biogen has exercised its Option (as defined in the 2012 Biogen License) with respect to Spinraza in accordance with Section 3.1.3 of the 2012 Biogen License and in accordance with the timeline set forth therein.&#160; The Seller has not developed any
      Follow-On Compound (as defined in the 2012 Biogen License) and Biogen has not exercised its right of first negotiation to develop and commercialize any Follow-On Compound pursuant to Section 2.1.2 of the 2012 Biogen License, except for BIIB-115. The
      Seller has not received or provided any notice pursuant to Section 6.6.1 of the 2012 Biogen License.</div>
    <div>&#160;</div>
    <div style="text-indent: 67.5pt; margin-left: 76.5pt;"><font style="color: rgb(1, 0, 0);">(B)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Biogen has exercised its Option (as defined in the 2017 Biogen License) with respect to BIIB-115 in accordance with Section 3.2 of the 2017
      Biogen License and in accordance with the timeline set forth therein.</div>
    <div>&#160;</div>
    <div style="text-indent: 67.5pt; margin-left: 76.5pt;"><font style="color: rgb(1, 0, 0);">(C)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Novartis has exercised its Option (as defined in the Novartis License) with respect to Pelacarsen in accordance with Section 3.3.2 of the
      Novartis License and in accordance with the timeline set forth therein.&#160; Neither Akcea nor the Seller has exercised, or delivered any notice or otherwise expressed an intent to Novartis to exercise, its right to co-commercialize Pelacarsen pursuant
      to Section 6.5 of the Novartis License.</div>
    <div>&#160;</div>
    <div style="text-indent: 31.5pt; margin-left: 76.5pt;"><font style="color: rgb(1, 0, 0);">(xv)</font>&#160;&#160;&#160;&#160;&#160;&#160; <u>Regulatory</u>. Since January 1, 2021 in the case of the 2012 Biogen License and since December 21, 2021 in the case of the 2017 Biogen
      License, the Seller has not received (A) any material regulatory reports (or feedback related thereto) pursuant to Section 5.15 of the 2012 Biogen License or Section 5.2.2 of the 2017 Biogen License, or (B) any other material update from Biogen&#8217;s
      Alliance Managers (designated in accordance with Section 1.2.6 of the 2012 Biogen License or Section 1.3.5 of the 2017 Biogen License), the substance of which, regarding clauses (A) and (B), has not been disclosed in the Data Room.&#160; Since January 1,
      2021, the Seller has not received (1) any material regulatory reports (or feedback related thereto) pursuant to Section 6.6 of the Novartis License, or (2) any other material update from Novartis&#8217; Alliance Manager (designated in accordance with
      Section 2.2 of the Novartis License) relating to Pelacarsen, the substance of which, regarding clauses (1) and (2), has not been disclosed in the Data Room.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(j)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Title to Royalty</u>. The Seller has good and marketable title to each of the BIIB-115 Royalty, Spinraza Royalty and Pelacarsen Royalty, free and clear of all
      Liens except for Permitted Liens. Upon payment of the Initial Purchase Price by the Buyer, the Buyer will acquire, subject to the terms and conditions set forth in this Agreement and the License Agreements, good and marketable title to the Purchased
      Royalty Payments, free and clear of all Liens (other than Liens created, permitted or required by this Agreement in favor of the Buyer or its Affiliates). </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">25</font></div>
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    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(k)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Intellectual Property</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt; color: rgb(1, 0, 0);">(i)</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(A)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Schedule 4.1(k)(i)(A)(1)</u> of the Disclosure Schedule lists all Ionis Product-Specific Spinraza Patents that were owned by Seller at the
      time Biogen obtained its license under Section 4.1.1 of the 2012 Biogen License, and all Jointly-Owned Spinraza Program Patents covering Spinraza (collectively, the &#8220;<u>Spinraza Assigned Patents</u>&#8221;).&#160; The Spinraza Assigned Patents were assigned to
      Biogen in accordance with Section 4.2 of the 2012 Biogen License.&#160;&#160; <u>[***]</u> (collectively, the &#8220;<u>Spinraza Licensed Patents</u>&#8221;). <u>Schedules 4.1(k)(i)(A)(1) and (2)</u> of the Disclosure Schedule specifies as to each of the Spinraza
      Assigned Patents and Spinraza Licensed Patents, (x) the jurisdictions by or in which each such patent has issued as a patent or such patent application has been filed, including the respective patent numbers and application numbers and issue and
      filing dates, and (y) the owner of such Patent Right, and (z) the expiration date of such Patent Right.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(B)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>[***]</u> (collectively, the &#8220;<u>BIIB-115 Licensed Patents</u>&#8221;).&#160; The Seller and Biogen collectively are the sole owners of each
      Jointly-Owned BIIB-115 Program Patent.&#160; The Seller is the sole owner of all of the BIIB-115 Licensed Patents (excluding Jointly-Owned BIIB-115 Program Patents), and its undivided half interest in each of the Jointly-Owned BIIB-115 Program Patents.&#160; <u>Schedule




        4.1(k)(i)(B)</u> of the Disclosure Schedule specifies as to each of the BIIB-115 Licensed Patents, (x) the jurisdictions by or in which each such patent has issued as a patent or such patent application has been filed, including the respective
      patent numbers and application numbers and issue and filing dates, and (y) the owner of such Patent Right, and (z) the expiration date of such Patent Right.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 108pt;"><font style="color: rgb(1, 0, 0);">(C)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>[***]</u> (collectively, the &#8220;<u>Pelacarsen Licensed Patents</u>&#8221;) and, to the Seller&#8217;s Knowledge, all Novartis Pelacarsen Program Patents.&#160;
      The Seller and Novartis collectively are the sole owners of each Jointly-Owned Pelacarsen Program Patent.&#160; The Seller is the sole owner of all of the Pelacarsen Licensed Patents, and its undivided half interest in each of the Jointly-Owned Pelacarsen
      Program Patents.&#160; <u>Schedule 4.1(k)(i)(C)</u> of the Disclosure Schedule specifies as to each of the Pelacarsen Licensed Patents: (x) the jurisdictions by or in which each such patent has issued as a patent or such patent application has been
      filed, including the respective patent numbers and application numbers and issue and filing dates, and (y) the owner of such Patent Right, and (z) the expiration date of such Patent Right.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">26</font></div>
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Except as set forth in <u>Schedule 4.1(k)(ii)</u> of the Disclosure Schedule, to the Knowledge of the Seller, there are no pending or threatened
      litigations, interferences, reexamination, reissues, <font style="font-style: italic;">inter partes </font>reviews, post-grant reviews, oppositions or like procedures involving any Spinraza Licensed Patents, Biogen Spinraza Patents, BIIB-115
      Licensed Patents, Biogen BIIB-115 Patents, Pelacarsen Licensed Patents or Novartis Pelacarsen Patents.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, all of the issued Spinraza Licensed Patents, BIIB-115 Licensed Patents, and Pelacarsen Licensed Patents are in
      full force and effect and none have lapsed, expired or otherwise terminated except in the ordinary course of business or naturally upon expiration of patent term, and, to the Knowledge of the Seller, all of the issued Spinraza Licensed Patents,
      Biogen Spinraza Patents, BIIB-115 Licensed Patents, Biogen BIIB-115 Patents, Pelacarsen Licensed Patents and Novartis Pelacarsen Patents are valid and enforceable. The Seller has not received any written notice relating to the lapse, expiration or
      other termination of any of the Spinraza Licensed Patents, Biogen Spinraza Patents, BIIB-115 Licensed Patents, Biogen BIIB-115 Patents, Pelacarsen Licensed Patents, or Novartis Pelacarsen Patents, or any written legal opinion that alleges that any of
      the issued Spinraza Licensed Patents, Biogen Spinraza Patents, BIIB-115 Licensed Patents, Biogen BIIB-115 Patents, Pelacarsen Licensed Patents, or Novartis Pelacarsen Patents are invalid or unenforceable.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, there is no Person who is or claims to be an inventor under any of the Spinraza Licensed Patents, BIIB-115 Licensed
      Patents, or Pelacarsen Licensed Patents who is not a named inventor thereof.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(v)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Seller has not, and, to the Knowledge of the Seller, no Licensee has, received any written notice of any claim by any Person (A) challenging
      the inventorship or ownership of, the rights of the Seller, Biogen, Novartis, UMass, Cold Spring Harbor or Akcea, as applicable, in and to, or the patentability, validity or enforceability of, any Spinraza Licensed Patent, Biogen Spinraza Patent,
      BIIB-115 Licensed Patent, Biogen BIIB-115 Patent, Pelacarsen Licensed Patent or Novartis Pelacarsen Patent, or (B) asserting that the development, manufacture, importation, sale, offer for sale or use of any Royalty Product infringes any patent or
      other intellectual property rights of such Person. The Seller has not received any written notice from any Licensee indicating that such Licensee has received any such written notice.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(vi)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, the discovery, development, manufacture, use, marketing, sale, offer for sale, importation or distribution of the
      Royalty Products did not and will not infringe or misappropriate any currently existing and published Patent Rights or other intellectual property rights owned by any Third Party that are not included in the Biogen Spinraza Patents, Biogen BIIB-115
      Patents, or Novartis Pelacarsen Patents. Neither the Seller nor, to the Knowledge of the Seller, Biogen or Novartis, has (except, with respect to Spinraza only, pursuant to the UMass License and the Cold Spring Harbor License) in-licensed any patents
      or other intellectual property rights covering the manufacture, use, sale, offer for sale or import of the Royalty Products.&#160; Akcea has not (except pursuant to the Pelacarsen Upstream Licenses) in-licensed any patents or other intellectual property
      rights covering the manufacture, use, sale, offer for sale or import of the Royalty Products. For purposes of Section 4.1(k)(vi), Patent Rights refers to a claim of an issued patent or a publicly available patent application.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">27</font></div>
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(vii)</font>&#160;&#160;&#160;&#160;&#160;&#160; To the Knowledge of the Seller, no Third Party has infringed, misappropriated or otherwise violated, or is infringing, misappropriating or
      otherwise violating, any Spinraza Licensed Patent, Biogen Spinraza Patent, BIIB-115 Licensed Patent, Biogen BIIB-115 Patent, Pelacarsen Licensed Patent or Novartis Pelacarsen Patent. All required maintenance fees, annuities and like payments with
      respect to the Spinraza Licensed Patents for which the Seller controls the prosecution and maintenance in accordance with Section 7.3 of the 2012 Biogen License, and to the Knowledge of the Seller, with respect to all other Spinraza Licensed Patents
      and Biogen Spinraza Patents, have been paid timely.&#160; All required maintenance fees, annuities and like payments with respect to the BIIB-115 Licensed Patents for which the Seller controls the prosecution and maintenance in accordance with Section 7.3
      of the 2017 Biogen License, and to the Knowledge of the Seller, with respect to all other BIIB-115 Licensed Patents and Biogen BIIB-115 Patents, have been paid timely. All required maintenance fees, annuities and like payments with respect to the
      Pelacarsen Licensed Patents for which the Seller controls the prosecution and maintenance in accordance with Section 8.4 of the Novartis License, and to the Knowledge of the Seller, with respect to all other Pelacarsen Licensed Patents and Novartis
      Pelacarsen Patents, have been paid timely. For purposes of this Section 4.1(k)(vii), Patent Rights refers to a claim of an issued patent.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(l)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>UCC Representation and Warranties</u>. (i) The Seller&#8217;s exact legal name is, and, since December 18, 2015, has been, &#8220;Ionis Pharmaceuticals, Inc.&#8221;, and, since its
      incorporation until and including December 17, 2015, the Seller&#8217;s exact legal name was, &#8220;Isis Pharmaceuticals, Inc.&#8221; and (ii) Akcea&#8217;s exact legal name is, and, since October 12, 2020, has been, &#8220;Akcea Therapeutics, Inc.&#8221; The Seller is, and for the
      prior ten (10) years has been, and Akcea is, and for the prior two (2) years has been incorporated in Delaware. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(m)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Brokers&#8217; Fees</u>. Except for Cowen Inc., there is no investment banker, broker, finder, financial advisor or other intermediary who has been retained by or is
      authorized to act on behalf of the Seller who might be entitled to any fee or commission in connection with the transactions contemplated by this Agreement. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(n)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Taxes</u>. The Seller has not received written notice from any Licensee, and is not otherwise aware, of any intention to withhold or deduct any tax from future
      payments to the Seller or Akcea. There are no audits or investigations (and the Seller has not been informed or notified of any pending audits or investigations by any tax authority) with respect to any payment made to the Seller or Akcea under any
      of the License Agreements that would reasonably be expected to have a Material Adverse Effect. To the knowledge of the Seller, none of the License Agreements are treated as a partnership for U.S. tax purposes and the Seller has never taken the
      position for U.S. federal income or other tax purposes that any of the License Agreements are treated as such. The Seller has never received a K-1 or other U.S. tax form furnished to a partner in a partnership as a result of being a party to any of
      the License Agreements.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">28</font></div>
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 4.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>The Buyer&#8217;s Representations and Warranties</u>. The Buyer represents and warrants to the Seller that as of the Closing Date: </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Existence; Good Standing</u>. The Buyer is an Irish collective asset-management vehicle that is duly organized, validly existing and in good standing under the
      laws of the Republic of Ireland.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Authorization</u>. The Buyer has the requisite right, power and authority to execute, deliver and perform its obligations under this Agreement. The execution,
      delivery and performance of this Agreement, and the consummation of the transactions contemplated hereby, have been duly authorized by all necessary action on the part of the Buyer.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Enforceability</u>. This Agreement has been duly executed and delivered by an authorized person of the owner trustee of the Buyer and constitutes the valid and
      binding obligation of the Buyer, enforceable against the Buyer in accordance with its terms, except as may be limited by applicable Bankruptcy Laws or by general principles of equity (whether considered in a proceeding in equity or at law).</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Conflicts</u>. The execution, delivery and performance by the Buyer of this Agreement do not and shall not (i) contravene or conflict with the organizational
      documents of the Buyer, (ii) contravene or conflict with or constitute a default under any material provision of any law binding upon or applicable to the Buyer or (iii) contravene or conflict with or constitute a default under any material contract
      or other material agreement or Judgment binding upon or applicable to the Buyer.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Consents</u>. Other than the filing of financing statement(s) in accordance with Section 2.3 or filings required by federal securities laws or stock exchange
      rules, no consent, approval, license, order, authorization, registration, declaration or filing with or of any Governmental Entity or other Person is required to be done or obtained by the Buyer in connection with (i) the execution and delivery by
      the Buyer of this Agreement, (ii) the performance by the Buyer of its obligations under this Agreement, or (iii) the consummation by the Buyer of any of the transactions contemplated by this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(f)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Litigation</u>. There is no action, suit, investigation or proceeding pending or, to the knowledge of the Buyer, threatened before any Governmental Entity to
      which the Buyer is a party that would, if determined adversely, reasonably be expected to prevent or materially and adversely affect the ability of the Buyer to perform its obligations under this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(g)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Financing</u>. The Buyer has sufficient cash on hand to pay the Purchase Price. The Buyer acknowledges that its obligations under this Agreement are not
      contingent on obtaining financing.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">29</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(h)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Brokers&#8217; Fees</u>. There is no investment banker, broker, finder, financial advisor or other intermediary who has been retained by or is authorized to act on
      behalf of the Buyer who might be entitled to any fee or commission in connection with the transactions contemplated by this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 4.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Implied Representations and Warranties</u>. EXCEPT AS EXPRESSLY SET FORTH IN SECTION 4.1, THE SELLER MAKES NO REPRESENTATION OR WARRANTY, EXPRESSED OR
      IMPLIED, AT LAW OR IN EQUITY, INCLUDING WITH RESPECT TO MERCHANTABILITY OR FITNESS FOR ANY PARTICULAR PURPOSE, AND ANY SUCH REPRESENTATIONS OR WARRANTIES ARE HEREBY EXPRESSLY DISCLAIMED. THE BUYER ACKNOWLEDGES THAT, EXCEPT AS SPECIFICALLY PROVIDED IN
      THIS ARTICLE 4 AND THE DISCLOSURE SCHEDULES, THE SELLER HAS ASSUMED NO RESPONSIBILITIES OF ANY KIND WITH RESPECT TO ANY ACT OR OMISSION OF ANY LICENSEE WITH RESPECT TO THE DESIGN, DEVELOPMENT, MANUFACTURE, USE, SALE, DISTRIBUTION, MARKETING OR OTHER
      ACTIVITIES OF SUCH LICENSEE WITH RESPECT TO ANY OF THE ROYALTY PRODUCTS. </div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 5</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">COVENANTS</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Disclosures</u>. Except for a press release previously approved in form and substance by the Seller and the Buyer or any other public announcement using
      substantially the same text as such press release or any other public disclosure permitted under this Agreement following the Closing, neither the Buyer nor the Seller shall, and each party hereto shall cause its respective Representatives,
      Affiliates and Affiliates&#8217; Representatives not to, issue a press release or other public announcement or otherwise make any public disclosure with respect to this Agreement or the subject matter hereof without the prior written consent of the other
      party hereto (which consent shall not be unreasonably withheld, conditioned or delayed), except as may be required by applicable law or stock exchange rule (in which case the party hereto required to make the press release or other public
      announcement or disclosure shall allow the other party hereto reasonable time to comment on such press release or other public announcement or disclosure in advance of such issuance and consider in good faith any comments provided by the other party
      on such proposed disclosure); provided that neither the Seller nor the Buyer shall be required to provide the other party the opportunity to review and comment on any disclosure required by applicable law or stock exchange rule relating to the
      accounting or tax treatment of the transactions contemplated hereby, so long as such disclosure is not inconsistent with Section 5.18. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Payments Received In Error</u>.</div>
    <div style="text-indent: 72pt;"><br>
    </div>
    <div style="text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Without limiting Section 2.1(e), commencing on the Closing Date and at all times thereafter, if any payment of any portion of the Purchased Royalty Payments is made to the Seller (or to any of the Seller&#8217;s
      Affiliates or designees), the Seller shall pay such amount to the Buyer or the Escrow Agent, promptly (and in any event within [***] Business Days) after the receipt thereof, by wire transfer to the Escrow Account or an account designated in writing
      by the Buyer. The Seller shall notify the Buyer of such wire transfer and provide reasonable details regarding the Purchased Royalty Payments so received by the Seller. Without limiting Section 2.1(e), the Seller agrees that, in the event any
      Purchased Royalty Payments is paid to the Seller, the Seller shall (i) until paid to the Buyer or Escrow Agent, hold such payment received in trust for the benefit of the Buyer and (ii) have no right, title or interest in such payment and that it
      shall not pledge or otherwise grant any security interest therein.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">30</font></div>
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    </div>
    <div style="text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Without limiting Section 2.1(e), commencing on the Closing Date and at all times thereafter, if any payment due under the License Agreements that does not constitute any Purchased Royalty Payments is made to
      the Buyer, the Buyer shall pay such amount to the Seller or the Escrow Agent, promptly (and in any event within [***] Business Days) after the receipt thereof, by wire transfer to the Escrow Account or an account designated in writing by the Seller.
      The Buyer shall notify the Seller of such wire transfer and provide reasonable details regarding the erroneous payment so received by the Buyer.&#160; Without limiting Section 2.1(e), the Buyer agrees that, in the event any payment due under the License
      Agreements that does not constitute Purchased Royalty Payments is paid to the Buyer, the Buyer shall (i) until paid to the Seller or Escrow Agent, hold such payment received in trust for the benefit of the Seller and (ii) have no right, title or
      interest in such payment and that it shall not pledge or otherwise grant any security interest therein.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Royalty Reduction</u>. If any Licensee exercises a Royalty Reduction (other than a Permitted Reduction) or Set-Off against any portion of the Purchased
      Royalty Payments, then the Seller shall promptly (and in any event within[***] Business Days following the payment of the Royalty affected by such Royalty Reduction or Set-Off) make a true-up payment to the Buyer such that the Buyer receives the full
      amount of such Purchased Royalty Payments that would have been payable to the Buyer had such Royalty Reduction or Set-Off not occurred. Notwithstanding anything to the contrary herein, to the extent Seller shall have made a true-up payment to the
      Buyer pursuant to this Section 5.3 in respect of any such Royalty Reduction or Set-Off, any subsequent payments received from a Licensee in respect, and to the extent, of such Royalty Reduction or Set-Off, whether pursuant to Section 10.4.4 of the
      2012 Biogen License, Section 10.4.5 of the 2017 Biogen License or otherwise, shall not be considered a Purchased Royalty Payment. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.4</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Late Fee</u>.A late fee of [***]% over the Prime Rate shall accrue on all unpaid amounts on an annualized basis with respect to any sum that is otherwise
      payable by the Buyer or by the Seller to the other party under this Agreement. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.5</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Royalty Reports; Notices and Other Information from Licensee</u><u>s</u>. </div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Promptly (and in any event within [***] Business Days) following the receipt by the Seller of any Royalty Report or other 2012 Biogen License Material Communications, 2017 Biogen License Material
      Communications, or Novartis License Material Communications, the Seller shall furnish a true, correct and complete copy of the same to the Buyer, to the extent such Royalty Reports are not already provided directly to the Buyer by Biogen or Novartis,
      and the Seller shall use commercially reasonable efforts to provide copies of all written communications that would reasonably be expected to be material to an owner of any of the Royalties.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">31</font></div>
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    </div>
    <div style="text-indent: 36pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Following the Closing, the Seller shall use commercially reasonable efforts to cause each of Biogen and Novartis to deliver copies of the applicable Royalty Reports to the Buyer.&#160; For purposes of Sections
      5.5(b)-(d) only, &#8220;commercially reasonably efforts&#8221; shall [***].</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Following the Closing, the Seller shall use commercially reasonable efforts to obtain Biogen&#8217;s signature to the Biogen Trilateral Common Interest Agreement (with such reasonable changes thereto as may be
      requested by Biogen, including to use an alternative, customary form of agreement if so requested by Biogen). Upon obtaining such signature from Biogen, the Seller shall execute and deliver the Biogen Trilateral Common Interest Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Following the Closing, the Seller shall use commercially reasonable efforts to obtain Novartis&#8217;s signature to the Novartis Trilateral Common Interest Agreement (with such reasonable changes therein as may be
      requested by Novartis, including to use an alternative, customary form of agreement if so requested by Novartis).&#160; Upon obtaining such signature from Novartis, the Seller shall execute and deliver the Novartis Trilateral Common Interest Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(e)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;At the request of the Buyer, no more than once per Calendar Year, the Buyer may provide [***]) days&#8217; prior written notice to the Seller, notifying the Seller of its request for a meeting and the parties
      shall meet (such meetings to be conducted via teleconference or videoconference unless the parties mutually agree otherwise) to discuss material developments in the development and commercialization of the Royalty Products.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(f)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;At the request of the Buyer, no more than once per Calendar Year, within [***] days of such request, the Seller shall deliver to Buyer an updated version of Schedule 4.1(k)(i)(A), 4.1(k)(i)(B), and
      4.1(k)(i)(C).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(g)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Within [***] Business Days of Closing, the Seller shall deliver to the Buyer the Biogen Instruction Letter and the Novartis Instruction Letter, in the forms attached hereto as <u>Exhibit C-1</u> (the &#8220;<u>Biogen




        Instruction Letter</u>&#8221;) and <u>Exhibit C-2</u> (the &#8220;<u>Novartis Instruction Letter</u>&#8221;), respectively, each duly executed by the Seller or Akcea, as applicable, instructing each of Biogen and Novartis to pay the SMA Royalties and the Pelacarsen
      Royalty, respectively, to the Escrow Agent, which the Seller shall deliver to each of Biogen and Novartis promptly (and in any event within [***] Business Days) following the delivery thereof to the Buyer.</div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.6</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Notices and Other Information to Licensee</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;So long as no SMA RP Control Shift has occurred and is continuing, the Seller shall (i) send to the Buyer a copy of any Material Correspondence that the Seller
      proposes to deliver to Biogen or any of its Affiliates, at least [***] Business Days prior to the proposed date for providing such Material Correspondence, (ii) consult with and consider in good faith any comments or requests from the Buyer regarding
      such proposed Material Correspondence,&#160; (iii) thereafter act reasonably regarding such Material Correspondence and matters related thereto and (iv) in no event, except as required to comply with the terms of this Agreement or the 2012 Biogen License
      or the 2017 Biogen License, as the case may be, send any Material Correspondence to Biogen that would reasonably be expected to result in a Material Adverse Effect (it being understood that the occurrence of a Material Adverse Effect may be the
      subject of, or trigger the Seller&#8217;s sending of, such correspondence).&#160; [***]</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">32</font></div>
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;So long as no Pelacarsen RP Control Shift has occurred and is continuing, the Seller shall (and shall cause Akcea to) (i) send to the Buyer a copy of any Material
      Correspondence that the Seller or Akcea proposes to deliver to Novartis or any of its Affiliates, at least [***] Business Days prior to the proposed date for providing such Material Correspondence, (ii) consult with and consider in good faith any
      comments or requests from the Buyer regarding such proposed Material Correspondence, (iii) thereafter act reasonably regarding such Material Correspondence matters related thereto and (iv) in no event, except as required to comply with the terms of
      this Agreement or the Novartis License, send any Material Correspondence to Novartis that would reasonably be expected to result in a Material Adverse Effect (it being understood that the occurrence of a Material Adverse Effect may be the subject of,
      or trigger the Seller&#8217;s (or Akcea&#8217;s) sending of, such correspondence). [***]</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.7</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Inspections and Audits of Licensee</u>.&#160; If either party desires to cause an inspection as provided under Section 6.10 of the 2012 Biogen License, Section
      6.10 of the 2017 Biogen License, or Section 7.12 of the Novartis License, for the Purchased Royalty Payments due and payable after the Closing Date then the Seller and the Buyer agree to consult in good faith with each other in connection therewith.&#160;
      Following such consultation, the Seller may, or if requested by the Buyer, shall (and shall cause Akcea to, as applicable), promptly provide written notice to Biogen or Novartis, as applicable, to cause such an inspection.&#160; With respect to any such
      inspection or audit required by the Buyer, the Seller shall (and shall cause Akcea to, as applicable), for purposes of Section 6.10 of the 2012 Biogen License, Section 6.10 of the 2017 Biogen License, or Section 7.12 of the Novartis License, as
      applicable, select Deloitte &amp; Touche LLP or such other independent public accounting firm as reasonably designated by the Buyer for such purpose (as long as, in the case of an audit pursuant to Section 7.12 of the Novartis License, such
      independent certified public accountant is reasonably acceptable to Novartis).&#160; The Buyer shall be responsible for the expense of any inspection or audit that would otherwise be borne by (and that were actually incurred by) the Seller pursuant to the
      2012 Biogen License or 2017 Biogen License only if such inspection or audit is undertaken at the Buyer&#8217;s request, and the Seller shall otherwise be responsible for all such expenses.&#160; The Buyer shall be responsible for the expense of any inspection
      or audit that would otherwise be borne by (and that were actually incurred by) the Seller or Akcea pursuant to the Novartis License only if such inspection or audit is undertaken at the Buyer&#8217;s request, and the Seller or Akcea shall otherwise be
      responsible for all such expenses. For the avoidance of doubt, nothing in this section shall obligate the Seller to exercise any inspection or audit that is not otherwise permitted under Section 6.10 of the 2012 Biogen License, Section 6.10 of the
      2017 Biogen License, or Section 7.12 of the Novartis License. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.8</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Amendment of License Agreement</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;">(a)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Seller proposes to amend, modify, provide a consent or waiver, or otherwise to take any action under the 2012 Biogen License or the 2017 Biogen License, so long as no SMA RP Control Shift has occurred
      and is continuing, the Seller shall (i) send to the Buyer a copy of any such proposed amendment, modification, consent, or waiver, or a description of such any other action that the Seller intends to take under the 2012 Biogen License or the 2017
      Biogen License, at least [***] Business Days prior to the proposed date for providing such document to Biogen or taking such action, (ii) consult with the Buyer regarding such document or action and consider any comments and requests from the Buyer
      regarding such document or action in good faith, (iii) thereafter act reasonably regarding such document or action and matters related thereto and (iv) in no event take any such action that would reasonably be expected to result in a Material Adverse
      Effect; provided that for any informal or ordinary course consent or other action that the Seller intends to take under the 2012 Biogen License or the 2017 Biogen License, clauses (i) and (ii) above shall apply solely to such consent or other action
      relates to the SMA Royalties or would reasonably be expected to have a Material Adverse Effect.&#160; [***]</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">33</font></div>
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    </div>
    <div style="text-indent: 72pt;">(b)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If the Seller proposes to amend, modify, provide a consent or waiver, or otherwise to take any action under the Novartis License, so long as no Pelacarsen RP Control Shift has occurred and is continuing, the
      Seller shall (and shall cause Akcea to) (i) send to the Buyer a copy of any such proposed amendment, modification, consent, notice or waiver, or a description of such any other action that the Seller or Akcea intends to take under the Novartis
      License, at least [***] Business Days prior to the proposed date for providing such document to Novartis or taking such action, (ii) consult with the Buyer regarding such document or action, and consider any comments and requests from the Buyer
      regarding such document or action in good faith, (iii) thereafter act reasonably regarding such document or action and matters related thereto and (iv) in no event take any such action (or fail to take any action) that would reasonably be expected to
      result in a Material Adverse Effect; provided that for any informal or ordinary course consent or other action that the Seller intends to take under the Novartis License, clauses (i) and (ii) above shall apply solely to such consent or other action
      relates to the Pelacarsen Royalty or would reasonably be expected to have a Material Adverse Effect.&#160; [***]</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Subject to the foregoing, promptly, and in any event within [***] Business Days, following receipt by the Seller (or Akcea) of any final amendment, modification, supplement or restatement of any License
      Agreement, the Seller shall furnish a copy of the same to the Buyer.</div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.9</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Maintenance of License Agreement</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 76.5pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Seller shall comply with its obligations under the Spinraza Upstream Licenses, including compliance with all payment obligations to UMass and Cold Spring Harbor
      pursuant to the Spinraza Upstream Licenses, and shall not take any action or forego any action that would reasonably be expected to constitute a breach thereof or default thereunder, except in each case as would not reasonably be expected (with or
      without the giving of notice or the passage of time) to have a Material Adverse Effect. Promptly, and in any event within [***] Business Days, after receipt of any written&#160; notice from UMass or Cold Spring Harbor, as the case may be, of an alleged
      breach or default under the UMass License or Cold Spring Harbor License that would reasonably be expected (with or without the giving of notice or passage of time, or both) to have a Material Adverse Effect, the Seller shall give notice thereof to
      the Buyer, including delivering the Buyer a copy of any such written notice.&#160; The Seller shall (i) consult with the Buyer regarding any such alleged breach or default under the UMass License or Cold Spring Harbor License and consider in good faith
      Buyer&#8217;s comments and requests regarding Seller&#8217;s response to such breach or default, including any dispute thereof, (ii) thereafter act reasonably regarding such alleged breach or default, including in connection with any dispute thereof, and matters
      related thereto, and (iii) not take any action (or fail to take any action) regarding any alleged breach or default that would reasonably be expected to result in a Material Adverse Effect.&#160; The Seller shall give written notice within [***] Business
      Days to the Buyer upon curing or otherwise settling any such breach or default.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">34</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 76.5pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Seller shall (and shall cause Akcea to) comply with its obligations under the Pelacarsen Upstream Licenses, including compliance with all payment obligations to
      Seller pursuant to the Pelacarsen Upstream Licenses, and shall not take any action or forego any action that would reasonably be expected to constitute a breach thereof or default thereunder, except in each case as would not reasonably be expected to
      have a Material Adverse Effect. Promptly, and in any event within [***] Business Days, after receipt by Seller or Akcea of any written notice from Alnylam, Akcea or Seller, respectively, of an alleged breach or default under any Pelacarsen Upstream
      License that would reasonably be expected (with or without the giving of notice or passage of time, or both) to have a Material Adverse Effect, the Seller shall give notice thereof to the Buyer, including delivering the Buyer a copy of any such
      written notice. The Seller shall (and shall cause Akcea to), (i) consult with the Buyer regarding such alleged breach or default and consider in good faith Buyer&#8217;s comments and requests regarding Seller&#8217;s or Akcea&#8217;s response to such breach or
      default, including any dispute thereof, (ii) thereafter act reasonably regarding such alleged breach or default, including in connection with any dispute thereof, and (iii) not (and shall cause Akcea not to) take any action (or fail to take any
      action) regarding any alleged breach or default that would reasonably be expected to result in a Material Adverse Effect.&#160; The Seller shall give written notice within [***] Business Days to the Buyer upon curing or settlement of any such breach or
      default.</div>
    <div>&#160;</div>
    <div style="text-indent: 18pt; margin-left: 58.5pt; color: rgb(1, 0, 0);">(c)</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Seller shall (and shall cause Akcea to) comply in all material respects with its obligations under the License Agreements and shall not take
      any action or forego any action that would reasonably be expected to constitute a material breach thereof or default thereunder. Promptly, and in any event within [***] Business Days, after receipt of any written notice from Biogen or Novartis, as
      the case may be, of any such alleged breach or default under any License Agreement, the Seller shall give notice thereof to the Buyer, including delivering the Buyer a copy of any such written notice. The Seller shall, subject to and in compliance
      with the provisions of this Section 5.9, consult with the Buyer regarding such alleged breach or default.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;After consultation with and after considering in good faith the Buyer&#8217;s comments, the Seller shall (and, if applicable, shall cause Akcea to) (i)
      act reasonably, including to use commercially reasonable efforts, to cure any such breach or default by the Seller or Akcea under the 2012 Biogen License, 2017 Biogen License, or Novartis License, as applicable, (ii) in connection therewith, not take
      any action (or fail to take any action) that would reasonably be expected to result in a Material Adverse Effect and (iii) give written notice to the Buyer upon curing any such breach or default.&#160; The Seller shall pay all of its costs and expenses
      (including of counsel), and shall cause Akcea to pay all of its costs and expenses (including of counsel), in connection with any such breach or default.</div>
    <div>&#160;</div>
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      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">35</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; [<u>Reserved.</u>]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; [***]</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;">(d)&#160; [***]</div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;">(e)&#160; [***]</div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.10</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Enforcement of License Agreement</u>s. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Notice of Breaches by Licensee</u>. Promptly (and in any event within [***] Business Days) after the Seller or Akcea becomes aware of, or comes to believe in good
      faith that there has been a material breach of any License Agreement by Biogen or Novartis, as the case may be, the Seller shall provide notice of such breach to the Buyer.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Enforcement of License Agreement</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Seller shall consult with the Buyer regarding the timing, manner and conduct of any enforcement of Biogen&#8217;s obligations or Novartis&#8217;
      obligations, as the case may be, under any License Agreement or regarding (a) any breach, default, disagreement or other dispute under any License Agreement that relates to the Royalty or that would reasonably be expected (with or without the giving
      of notice or passage of time) to have a Material Adverse Effect and (b) any other material breach, default, disagreement or other dispute under any License Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; Following such consultation set forth in clause (i) and so long as no SMA RP Control Shift has occurred and is continuing, the Seller shall
      consider in good faith all of Buyer&#8217;s timely comments and suggestions regarding any enforcement of Biogen&#8217;s obligations under the 2012 Biogen License or the 2017 Biogen License and, after such consideration, shall act reasonably regarding such
      enforcement.&#160; Following such consultation set forth in clause (i) and so long as no Pelacarsen RP Control Shift has occurred and is continuing, the Seller shall (and shall cause Akcea to) consider in good faith all of Buyer&#8217;s timely comments and
      suggestions regarding any enforcement of Novartis&#8217; obligations under the Novartis License and after such consultation shall act (or cause Akcea to act) reasonably regarding such enforcement.&#160;&#160; In connection with any such enforcement, the Seller shall
      not (and shall cause Akcea not to) take any action (or fail to take any action) regarding any breach, default, disagreement or other dispute under any License Agreement that would reasonably be expected to result in a Material Adverse Effect.</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; Following such consultation set forth in clause (i), during the occurrence and continuance of an SMA RP Control Shift, the Seller shall exercise
      such rights and remedies relating to any such breach, default, disagreement or other dispute related to the SMA Royalties only as reasonably instructed by the Buyer, whether under 2012 Biogen License or 2017 Biogen License or otherwise.&#160; Following
      such consultation set forth in clause (i), and during the occurrence and continuance of a Pelacarsen RP Control Shift, the Seller shall, and shall cause Akcea to, exercise such rights and remedies relating to any such breach, default, disagreement or
      other dispute related to the Pelacarsen Royalty only as reasonably instructed by the Buyer, whether under the Novartis License or otherwise. During the occurrence and continuance of an SMA RP Control Shift, the Seller shall employ such counsel,
      reasonably acceptable to the Seller, as the Buyer may select, and shall provide the Buyer with access to such counsel in connection with any breach, default, disagreement or other dispute under 2012 Biogen License or 2017 Biogen License or otherwise
      related to the SMA Royalty.&#160; During the occurrence and continuance of a Pelacarsen RP Control Shift, the Seller shall, and shall cause Akcea to, employ such counsel, reasonably acceptable to the Seller, as the Buyer may select, and shall provide the
      Buyer with access to such counsel in connection with any breach, default, disagreement or other dispute under the Novartis License or otherwise related to the Pelacarsen Royalty.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">36</font></div>
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; The Seller agrees to keep the Buyer reasonably informed of any actual or alleged breach, default, disagreement or other dispute set forth in clause
      (i) and to provide copies as soon as practicable, but in any event within [***] Business Days following the Seller&#8217;s or Akcea&#8217;s receipt or delivery of (A) any written notice of any such actual or alleged breach, default, disagreement or other dispute
      and (B) any and all material filings, notices and written communications relating thereto.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;">(c)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Allocation of Proceeds and Costs of Enforcement</u>. The Buyer shall reimburse the Seller (and if applicable, Akcea) for (i) as it relates to enforcement of Biogen&#8217;s obligations, for the period prior to
      January 1, 2028, 25%, and commencing January 1, 2028, 45%, and (ii) as it relates to enforcement of Novartis&#8217; obligations, 25%, of all fees and expenses incurred in enforcing Biogen&#8217;s obligations or Novartis&#8217; obligations, as the case may be, under
      any License Agreement pursuant to this Section 5.10, as such costs and expenses are incurred, in connection with any actions taken or exercise of rights and remedies by the Seller. The Proceeds resulting from any enforcement of Biogen&#8217;s obligations
      or Novartis&#8217; obligations, as the case may be, under any License Agreement shall be applied first to reimburse the Seller and the Buyer for any reasonable and documented expenses incurred by them in connection with such enforcement, with the remainder
      of the Proceeds distributed (i) to the Buyer (A) as it relates to a breach by Biogen, for the period prior to January 1, 2028, 25%, and commencing January 1, 2028, 45%, and (ii) as it relates to a breach by Novartis, 25%, and (ii) to the Seller for
      all remaining Proceeds. Each of the Seller and Akcea hereby assigns and, if not presently assignable, agrees to assign to the Buyer, the amount of Proceeds due to the Buyer in accordance with this Section 5.10(c).</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt;">(d)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.11</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>[***]</u></div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">37</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.12</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>[***]</u></div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.13</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Preservation of Rights</u><u>; No Material Adverse Effect</u>. Notwithstanding anything in this Agreement to the contrary but except as permitted under
      Section 9.3, the Seller shall not (i) impose or grant a Lien upon, or otherwise sell, transfer, hypothecate, assign, convey title (in whole or in part), grant any right to, or otherwise dispose of any portion of any Purchased Royalty Payments or any
      &#8220;proceeds&#8221; (as defined in the UCC) thereof, or (ii) enter into or deliver any Contracts (or make or propose any amendments, modifications waivers or notices in connection with any contracts or arrangements) related to the Royalty, solely with respect
      to this clause (ii) that would, individually or in the aggregate reasonably be expected to result in a Material Adverse Effect or otherwise take any action or fail to act with the specific intention to undermine the Royalty. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.14</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Enforcement; Defense; Prosecution and Maintenance</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Buyer and the Seller shall promptly inform each other of any suspected infringement by a Third Party they become aware of with respect to any of the Spinraza
      Licensed Patents, BIIB-115 Licensed Patents or Pelacarsen Licensed Patents in each case where such infringement would reasonably be expected to have a Material Adverse Effect. Seller shall (i) provide to the Buyer a copy of any written notice of any
      suspected infringement of any of the Spinraza Licensed Patents, BIIB-115 Licensed Patents, or Pelacarsen Licensed Patents where such infringement would reasonably be expected to have a Material Adverse Effect and all pleadings filed in such action
      and (ii) notify the Buyer of any material developments in any claim, suit or proceeding resulting from such infringement that are communicated by Biogen or Novartis, as the case may be, to the Seller under Sections 7.4 and 7.5 of the 2012 Biogen
      License, Sections 7.4 and 7.5 of the 2017 Biogen License, or Section 8.6.1 of the Novartis License or otherwise as soon as practicable and in any event not less than [***] Business Days following such delivery.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt; color: rgb(1, 0, 0);">(b)</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;So long as no SMA RP Control Shift has occurred and is continuing, to the extent the Seller has the right to, and exercises such right to, join or
      assume the defense or pursue an enforcement action pursuant to Sections 7.4 and 7.5 of the 2012 Biogen License or Sections 7.4 and 7.5 of the 2017 Biogen License, as applicable, the Seller shall use commercially reasonable efforts to (i) diligently
      defend or enforce any applicable Spinraza Licensed Patents or BIIB-115 Licensed Patents (including by bringing and defending any counterclaim of invalidity or unenforceability, defending against any action of a Third Party for declaratory judgment of
      non-infringement or non-interference or bringing any legal action for infringement) to the extent the failure to so defend or enforce would reasonably be expected to have a Material Adverse Effect and (ii) not disclaim or abandon, or fail to take any
      action necessary to prevent the disclaimer, abandonment or dismissal (including through lack of enforcement against Third Party infringers) of any defense of invalidity or unenforceability or any legal action for infringement of any Spinraza Licensed
      Patents or BIIB-115 Licensed Patents for which it has the right to, and has elected to, join or assume the defense or pursue an enforcement action pursuant to this Section 5.14(b), except as would not reasonably be expected to have a Material Adverse
      Effect.&#160; The Seller shall, if requested in writing by the Buyer, promptly, and in any event within [***] Business Days after receipt of such request, provide all reasonably requested documentation and information relating to such enforcement action
      to the Buyer. So long as no Pelacarsen RP Control Shift has occurred and is continuing, to the extent the Seller (or Akcea) has the right to, and exercises its right to, join or assume the defense or pursue an enforcement action pursuant to Section
      8.6.1 of the Novartis License, the Seller (or Akcea) shall use commercially reasonable efforts (i) diligently defend or enforce any applicable Pelacarsen Licensed Patents (including by bringing and defending any counterclaim of invalidity or
      unenforceability, defending against any action of a Third Party for declaratory judgment of non-infringement or non-interference or bringing any legal action for infringement) to the extent the failure to so defend or enforce would reasonably be
      expected to have a Material Adverse Effect and (ii) not disclaim or abandon, or fail to take any action necessary to prevent the disclaimer, abandonment or dismissal (including through lack of enforcement against Third Party infringers) of any
      defense of invalidity or unenforceability or any legal action for infringement of any Pelacarsen Licensed Patents for which it has the right to, and has elected to, join or assume the defense or pursue an enforcement action pursuant to this Section
      5.14(b), except as would not reasonably be expected to have a Material Adverse Effect.&#160; The Seller (or Akcea) shall, if requested in writing by the Buyer, promptly, and in any event within [***] Business Days after receipt of such request, provide
      all reasonably requested documentation and information relating to such enforcement action to the Buyer.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">38</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;[***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; [***]</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; To the extent Biogen or Novartis enforces any of the Ionis Spinraza Patents, Ionis BIIB-115 Patents, or Ionis Pelacarsen Patents together with any
      other patents owned or controlled by Biogen or Novartis, as applicable, the Seller agrees to negotiate in good faith with Biogen or Novartis, as applicable, and agree to a reasonable allocation of Proceeds as between the Ionis Spinraza Patents, Ionis
      BIIB-115 Patents, or Ionis Pelacarsen Patents and any other patents that were subject to such suit. In each such case, the Seller shall obtain and deliver to the Buyer an accounting detailing the Proceeds allocated to the Ionis Spinraza Patents,
      Ionis BIIB-115 Patents, or Ionis Pelacarsen Patents.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Seller shall (i) take any and all actions, and prepare, execute, deliver and file any and all agreements, documents and instruments, that it deems to be
      reasonably necessary to diligently prosecute, preserve and maintain any Spinraza Assigned Patents, Spinraza Licensed Patents, BIIB-115 Licensed Patents, Jointly-Owned Pelacarsen Program Patents, and Pelacarsen Licensed Patents for which it controls
      the prosecution and maintenance in accordance with Sections 7.2.2(a), 7.2.3, and 7.2.4 of the 2012 Biogen License, Section 7.2.2(a), 7.2.3 and 7.2.4 of the 2017 Biogen License, and Section 8.3.1 and 8.3.2 of the Novartis License, and including
      payment of maintenance fees or annuities on any such Patent Rights where the failure to so prosecute would reasonably be expected to have a Material Adverse Effect, (ii) prosecute any reasonably necessary corrections, substitutions, reissues, reviews
      and reexaminations, and any other forms of patent term restoration in any applicable jurisdiction, of any Spinraza Assigned Patents, Spinraza Licensed Patents, BIIB-115 Licensed Patents, Jointly-Owned Pelacarsen Program Patents, or Pelacarsen
      Licensed Patents for which it controls the prosecution and maintenance in accordance with Sections 7.2.2(a), 7.2.3 and 7.2.4 of the 2012 Biogen License, Sections 7.2.2(a), 7.2.3, and 7.2.4 of the 2017 Biogen License, and Sections 8.3.1 and 8.3.2 of
      the Novartis License where the failure to so prosecute would reasonably be expected to have a Material Adverse Effect, (iii) diligently enforce and defend any Spinraza Assigned Patents, Spinraza Licensed Patents, BIIB-115 Licensed Patents,
      Jointly-Owned Pelacarsen Program Patents, and Pelacarsen Licensed Patents for which it controls the defense and enforcement, including by bringing any legal action for infringement or defending any counterclaim of invalidity or unenforceability or
      action of a Third Party for declaratory judgment of non-infringement or non-interference, in accordance with Section 5.14(b) of this Agreement where the failure to so enforce or defend would reasonably be expected to have a Material Adverse Effect,
      and (iv) not disclaim or abandon, or fail to take any action necessary or desirable to prevent the disclaimer or abandonment (including through lack of enforcement against Third Party infringers) of any Spinraza Assigned Patents, Spinraza Licensed
      Patents, BIIB-115 Licensed Patents, Jointly-Owned Pelacarsen Program Patents, and Pelacarsen Licensed Patents for which it controls the prosecution and maintenance in accordance with Sections 7.2.2(a), 7.2.3, and 7.2.4 of the 2012 Biogen License,
      Sections 7.2.2(a), 7.2.3, and 7.2.4 of the 2017 Biogen License, and Sections 8.3.1 and 8.3.2 of the Novartis License, except as would not reasonably be expected to have a Material Adverse Effect.&#160; During the occurrence and continuance of an SMA RP
      Control Shift, any of the foregoing actions with respect to any Spinraza Assigned Patents, Spinraza Licensed Patents or BIIB-115 Licensed Patents shall be taken and during the occurrence and continuance of a Pelacarsen RP Control Shift, any of the
      foregoing actions with respect to any Jointly-Owned Pelacarsen Program Patents or Pelacarsen Licensed Patents shall be taken as reasonably instructed by the Buyer; provided that nothing herein shall require the Seller (or Akcea) to take any action in
      violation of the applicable License Agreement.&#160; The Seller agrees to keep the Buyer reasonably informed of the status of the prosecution and maintenance under the License Agreements.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">39</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Buyer shall reimburse the Seller for its reasonable and documented out-of-pocket legal costs and expenses incurred in connection with any enforcement actions
      taken by the Seller or Akcea pursuant to&#160; Sections 5.14(b)(i)(i), 5.14(b)(ii), 5.14(b)(iii), and 5.14(c)(iii) for which the Seller or Akcea is not entitled to reimbursement by a Licensee as follows: (A) as it relates to the Spinraza Assigned Patents,
      Spinraza Licensed Patents and BIIB-115 Licensed Patents, (i) for the period prior to January 1, 2028, 25%, (ii) for the period commencing January 1, 2028 and ending when the SMA Royalty Cap is achieved, 45%, and (iii) after the SMA Royalty Cap is
      achieved, 0%; and (B) as it relates to Jointly-Owned Pelacarsen Program Patents, and Pelacarsen Licensed Patents, 25%, of such costs and expenses.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.15</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Additional Monetizations</u>.&#160; The Seller agrees to notify the Buyer in writing at least [***] days prior to entering into a definitive agreement with a
      Third Party relating to a Seller Monetization Transaction. In the event the Seller provides a Third Party to a Seller Monetization Transaction with any more extensive, favorable, robust, or otherwise broader informational, inspection, consent,
      enforcement or other rights than any of those similar rights provided to the Buyer under any of Sections 5.5 (solely with respect to reporting related to the Royalty Products) through 5.12 (the &#8220;<u>Enhanced Rights</u>&#8221;), the Seller shall, subject to
      this Section 5.15, upon written request from the Buyer, provide the Buyer within [***] Business Days with a copy of the definitive agreement with a Third Party relating to such Seller Monetization Transaction, subject to redactions of sections not
      related to the Enhanced Rights, and the Buyer shall elect, by written notice to the Seller provided within [***] Business Days of receipt of such definitive agreement, whether it would like to (i) retain its existing rights under Sections 5.5 through
      5.12 hereunder, or (ii) replace its existing rights under Sections 5.5 through 5.12 hereunder with the Enhanced Rights, [***], <font style="font-style: italic;">mutadis mutandis</font>, effective upon the Seller&#8217;s receipt of such written notice. If
      the Buyer does not make an election by written notice within [***] Business Days of receipt of such definitive agreement, the Buyer shall be deemed to have elected to retain its existing rights under Sections 5.5 through 5.12 hereunder.
      Notwithstanding the foregoing, upon the Buyer&#8217;s written request for a copy of the definitive agreement, instead of providing a copy of the definitive agreement, the Seller may elect to deliver to the Buyer (a) a certificate signed by the Chief
      Executive Officer or Chief Financial Officer of the Seller in which the Seller certifies that the Seller did not provide Enhanced Rights in connection with such Seller Monetization Transaction or (b) a summary of any such Enhanced Rights that the
      Seller did provide in connection with such Seller Monetization together with a draft amendment to this Agreement memorializing the grant of such Enhanced Rights to the Buyer.&#160; If the Buyer elects to replace its existing rights with the Enhanced
      Rights, the Seller and the Buyer shall, acting reasonably, enter into an amendment to this Agreement within [***] Business Days of the consummation (or material amendment) of the Seller Monetization Transaction memorializing the replacement of the
      Buyer&#8217;s rights under Sections 5.5 through 5.12 hereunder with such Enhanced Rights, in whole and not in part, <font style="font-style: italic;">mutatis mutandis</font>.&#160; Within [***] Business Days of the consummation (or material amendment) of any
      Seller Monetization Transaction (or the earlier request of Seller pursuant to Exhibit K), the Seller and the Buyer, each acting reasonably and in good faith, shall also agree upon all then current SMA Royalty Percentages or Pelacarsen Royalty
      Percentages, as applicable, as determined in accordance with Exhibit K. </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">40</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.16</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Further Assurances</u>. After the Closing, the Seller and the Buyer agree to execute and deliver such other documents, certificates, agreements and other
      writings and to take such other actions as may be reasonably necessary in order to give effect to the transactions contemplated by this Agreement.&#160; Without limiting the foregoing, the Buyer shall ensure that it has sufficient capital to pay the
      Additional Purchase Price Payments as and when due. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.17</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Intercompany Relationship</u>. The Seller shall cause Akcea (a) to continue to operate the Akcea business in the ordinary course of its business, and to
      continue to be duly licensed and qualified to do business, and be in corporate good standing, in all material respects, in each jurisdiction necessary to continue to operation in the ordinary course of its business, and (b) to comply in all material
      respects with its obligations under the Pelacarsen Upstream Licenses and the Novartis License.&#160; [***]. Notwithstanding the foregoing, Akcea may consolidate with, merge with or into, liquidate into, or sell, convey, transfer or lease all or
      substantially all of its properties and assets to the Seller or any wholly-owned subsidiary of the Seller. </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">41</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 5.18</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Tax Matters</u>.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"></div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notwithstanding anything to the contrary in this Agreement, the Seller and the Buyer shall treat the transactions contemplated by this Agreement as a sale of the
      Purchased Royalty Payments for United States federal, state, local and non-U.S. Tax purposes. Accordingly, any and all Purchased Royalty Payments made pursuant to the License Agreements after the Closing Date shall be treated as sold to the Buyer for
      United States federal, state, local and non-U.S. Tax purposes. The parties shall cooperate to effect the foregoing treatment for United States federal, state, local and non-U.S. Tax purposes in the event that, notwithstanding the Biogen Instruction
      Letters and the Novartis Instruction Letter, any Licensee, any sublicensee or any other Person makes any future remittance of Purchased Royalty Payments to the Seller which the Seller must remit to the Buyer or the Escrow Agent pursuant to Section
      5.2(a) of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;All payments to the Seller under this Agreement shall be made without any deduction or withholding for or on account of any Tax unless required by applicable law.
      Provided that Seller provides the IRS Form W-9 called for by Section 3.5, each of the Buyer and the Seller agree that as of the date hereof there are no United States Federal and State withholding obligations under current law in respect of any
      payment to the Seller under this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The parties hereto agree not to take any position that is inconsistent with the provisions of this Section 5.18 on any Tax return or in any audit or other
      administrative or judicial proceeding unless (i) the other party hereto has consented in writing to such actions or (ii) the party hereto that contemplates taking such an inconsistent position has been advised by nationally recognized tax counsel in
      writing that there is no &#8220;reasonable basis&#8221; (within the meaning of Treasury Regulation Section 1.6662-3(b)(3)) for the position specified in this Section 5.18. If there is an inquiry by any Governmental Entity of the Seller or the Buyer related to
      this Section 5.18, the parties hereto shall cooperate with each other in responding to such inquiry in a reasonable manner consistent with this Section 5.18.</div>
    <div><br>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 6</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">CONFIDENTIALITY</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 6.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Confidentiality</u>. Except as provided in this Article 6 or otherwise agreed in writing by the parties, the parties hereto agree that, for the term of
      this Agreement and for [***] thereafter, each party (the &#8220;<u>Receiving Party</u>&#8221;) shall keep confidential and shall not publish or otherwise disclose and shall not use for any purpose other than as provided for in this Agreement (which includes the
      exercise of any rights or the performance of any obligations hereunder) any information furnished to it by or on behalf of the other party (the &#8220;<u>Disclosing Party</u>&#8221;) pursuant to this Agreement (such information, &#8220;<u>Confidential Information</u>&#8221;
      of the Disclosing Party), except for that portion of such information that: </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;was already known to the Receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the Disclosing Party;</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">42</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the Receiving
      Party in breach of this Agreement;</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(d)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;is independently developed by the Receiving Party or any of its Affiliates, as evidenced by written records, without the use of or reference of the Confidential
      Information of the Disclosing Party; or</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(e)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;is subsequently disclosed to the Receiving Party on a non-confidential basis by a Third Party without obligations of confidentiality with respect thereto.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 6.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Authorized Disclosure</u>. </div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Either party may disclose Confidential Information with the prior written consent, such consent not to be unreasonably withheld or delayed, of the Disclosing Party
      or to the extent such disclosure is reasonably necessary in the following situations:</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(i)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;complying with applicable laws, rules and regulations, including regulations promulgated by securities exchanges;</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(ii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; complying with a valid order of a court of competent jurisdiction or other Governmental Entity;</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iii)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; disclosure to its Affiliates and Representatives on a need-to-know basis, provided that each recipient of Confidential Information must be bound
      by obligations of confidentiality and non-use no less restrictive than the obligations set forth herein prior to any such disclosure; or</div>
    <div>&#160;</div>
    <div style="text-indent: 36pt; margin-left: 72pt;"><font style="color: rgb(1, 0, 0);">(iv)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; disclosure to its actual or potential lenders, potential acquirers, investors, merger partners, consultants, auditors or professional advisors,
      provided, that such disclosure shall be made only to the extent customarily required to consummate such investment, financing transaction partnership, collaboration or acquisition and that each recipient of Confidential Information must be bound by
      obligations of confidentiality and non-use no less restrictive than those in this Agreement prior to any such disclosure.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;Notwithstanding the foregoing, in the event the Receiving Party is required to make a disclosure of the Disclosing Party&#8217;s Confidential Information pursuant to
      Section 6.2(a)(i) or&#160; Section 6.2(a)(ii), it will, except where impracticable, give reasonable advance notice to the Disclosing Party of such disclosure and use reasonable efforts to secure confidential treatment of such information. In any event,
      the Buyer shall not file any patent application based upon or using the Confidential Information of Seller provided hereunder.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">43</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="color: rgb(1, 0, 0);">
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Buyer agrees that it shall (i) protect and safeguard the Confidential Information of the Seller or Akcea with at least the same degree of care as the Buyer
        would protect its own similar Confidential Information, but in no event with less than a commercially reasonable degree of care, (ii) not use the Seller&#8217;s Confidential Information, or permit it to be accessed or used, in violation of or
        inconsistent with this Article 6, and (iii) implement procedures to ensure no such Confidential Information is disclosed to any person or entity that are pharmaceutical companies that are developing or commercializing any product that is directly
        competitive with any 2012 Biogen Licensed Product, including Spinraza, 2017 Biogen Licensed Product, including BIIB-115, or Pelacarsen. Buyer acknowledges and agrees that any breach of this Article 6 will cause injury to the Seller for which money
        damages would be an inadequate remedy and that, in addition to remedies at law, the Seller is entitled to seek equitable relief as a remedy for any such breach.</div>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 7</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">INDEMNIFICATION</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>General Indemnity</u>. Subject to Section 7.3, from and after the Closing: </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the Seller hereby agrees to indemnify, defend and hold harmless the Buyer and its Affiliates and its and their directors, managers, trustees, officers, agents and
      employees (the &#8220;<u>Buyer Indemnified Parties</u>&#8221;) from, against and in respect of all Losses suffered or incurred by the Buyer Indemnified Parties to the extent arising out of or resulting from (i) any breach of any of the representations or
      warranties (in each case, when made) of the Seller in this Agreement or (ii) any breach of any of the covenants or agreements of the Seller or Akcea in this Agreement; provided, however, that the foregoing shall exclude any indemnification to any
      Buyer Indemnified Party to the extent resulting from (x) the gross negligence, willful misconduct, or fraud of any Buyer Indemnified Party or (y) acts or omissions of Seller or any of its Affiliates taken (or not taken) upon written instructions from
      any Buyer Indemnified Party (unless Seller is otherwise liable for such Losses pursuant to the terms of this Agreement); and</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;the Buyer hereby agrees to indemnify, defend and hold harmless the Seller and its Affiliates and its and their directors, officers, agents and employees (&#8220;<u>Seller
        Indemnified Parties</u>&#8221;) from, against and in respect of all Losses suffered or incurred by the Seller Indemnified Parties to the extent arising out of or resulting from (i) any breach of any of the representations or warranties (in each case,
      when made) of the Buyer in this Agreement or (ii) any breach of any of the covenants or agreements of the Buyer in this Agreement; provided, however, that the foregoing shall exclude any indemnification to any Seller Indemnified Party to the extent
      resulting from (x) the gross negligence, willful misconduct, or fraud of any Seller Indemnified Party or (y) acts or omissions of Buyer or any of its Affiliates taken (or not taken) upon written instructions from any Seller Indemnified Party (unless
      Buyer is otherwise liable for such Losses pursuant to the terms of this Agreement).</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">44</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Notice of Claims</u>. </div>
      <div>&#160;</div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If either a Buyer Indemnified Party, on the one hand, or a Seller Indemnified Party, on the other hand (such Buyer Indemnified Party on the one hand and such
        Seller Indemnified Party on the other hand being hereinafter referred to as an &#8221;<u>Indemnified Party</u>&#8221;), has suffered or incurred any Losses for which indemnification may be sought under this Article 7, the Indemnified Party shall so notify the
        other party from whom indemnification is sought under this Article 7 (the &#8220;<u>Indemnifying Party</u>&#8221;) promptly in writing (a &#8220;<u>Claim Notice</u>&#8221;) describing such Loss, the amount or estimated amount thereof (in each case, the &#8220;<u>Claim Amount</u>&#8221;),

        if known or reasonably capable of estimation, and the method of computation of such Loss, all with reasonable particularity and containing a reference to the provisions of this Agreement in respect of which such Loss shall have occurred. Within
        [***] days after delivery of a Claim Notice, the Indemnifying Party shall deliver to the Indemnified Party a written response in which the Indemnifying Party shall (i) agree that the Indemnified Party is entitled to receive the Claim Amount (in
        which case such response shall be accompanied by a payment to the Indemnified Party of the Claim Amount by the Indemnifying Party by wire transfer of immediately available funds), (ii) agree that the Indemnified Party is entitled to receive part,
        but not all, of the Claim Amount (the amount so agreed in (i) or (ii), the &#8220;<u>Agreed Amount</u>&#8221;) (in which case such response shall be accompanied by a payment to the Indemnified Party of the Agreed Amount by the Indemnifying Party by wire
        transfer of immediately available funds) or (iii) contest that the Indemnified Party is entitled to receive any of the Claim Amount. If such dispute is not resolved within [***] days following the delivery of the Indemnifying Party of such
        response, the Indemnifying Party and the Indemnified Party shall each have the right to submit such dispute to a court of competent jurisdiction in accordance with the provisions of Section 9.8.&#160; Failure of the Indemnifying Party to timely deliver
        a response as provided in this Section 7.2(a) shall not waive the Indemnifying Party&#8217;s ability to submit such dispute to a court of competent jurisdiction in accordance with the provisions of Section 9.8.</div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);"> <br>
      </font></div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;If any claim, action, suit or proceeding is asserted or instituted by or against a Third Party with respect to which an Indemnified Party intends to claim any Loss
      under this Article 7, such Indemnified Party shall promptly notify the Indemnifying Party of such claim, action, suit or proceeding and tender to the Indemnifying Party the defense of such claim, action, suit or proceeding.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;A failure by an Indemnified Party to give notice, including a Claim Notice, and to tender the defense of such claim, action, suit or proceeding in a timely manner
      pursuant to this Section 7.2 shall not limit the obligation of the Indemnifying Party under this Article 7, except to the extent such Indemnifying Party is actually prejudiced thereby.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Limitations on Liability</u>. </div>
    <div>&#160;</div>
    <div style="margin-left: 72pt; text-indent: 36pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Seller shall have liability under Section 7.1(a) with respect to any breach of any representation or warranty made by the Seller in this
      Agreement only if, on or prior to the date that is [***] after the Closing Date, the Buyer notifies the Seller of a claim in respect of such breach, specifying the factual basis of such claim and amount in reasonable detail (other than (x) [***] and
      (y) [***] as to which a claim may be made at any time until the date that is [***] after the termination of this Agreement).</div>
    <div>&#160;</div>
    <div style="margin-left: 72pt; text-indent: 36pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Buyer shall have liability under Section 7.1(b) with respect to any breach of any representation or warranty made by the Buyer in this
      Agreement, only if, on or prior to the date that is [***] after the Closing Date, the Seller notifies the Buyer of a claim in respect of such breach, specifying the factual basis of such claim and amount in reasonable detail (other than [***], as to
      which a claim may be made at any time until the date that is [***] after the termination of this Agreement.</div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">45</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="margin-left: 72pt; text-indent: 36pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;No party hereto shall be liable for any indirect, consequential, punitive, special or incidental damages (and no claim for indemnification
      hereunder shall be asserted) as a result of any breach or violation of any covenant or agreement of such party (including under this Article 7, but excluding Article 6) in or pursuant to this Agreement. Notwithstanding the foregoing, the Buyer shall
      be entitled to make indemnification claims, in accordance with the procedures set forth in this Article 7, for Losses that include any portion of the Purchased Royalty Payments that the Buyer was entitled to receive but did not receive timely or at
      all due to any indemnifiable events under this Agreement, and such portion of the Purchased Royalty Payments shall not be deemed indirect, consequential, punitive, special or incidental damages for any purpose of this Agreement. Notwithstanding the
      foregoing, other than with respect to any fraud, willful misconduct, or intentional misrepresentation, (i) in no event shall an Indemnifying Party&#8217;s aggregate liability for Losses under Section 7.1 exceed the [***] of the date hereof and (ii) no
      Indemnifying Party shall have any liability for Losses under Section 7.1(a)(i) or Section 7.1(b)(i), as the case may be, except to the extent the aggregate amount of all Losses incurred by the Indemnified Party equals or exceeds $[***], at which
      point the full amount of the Losses shall be recoverable; provided that the foregoing limitations shall not apply to any Losses arising from a failure by Buyer to pay any portion of the Purchase Price in accordance with Section 2.1.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.4</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Third Party Claims</u>. Following the receipt of notice provided by an Indemnified Party pursuant to Section 7.2 of the commencement of any action, suit
      or proceeding against such Indemnified Party by a Third Party with respect to which such Indemnified Party intends to claim any Loss under this Article 7, an Indemnifying Party shall have the right to defend such claim, at such Indemnifying Party&#8217;s
      expense and with counsel of its choice reasonably satisfactory to the Indemnified Party.&#160; If the Indemnifying Party assumes the defense of such claim, the Indemnified Party shall, at the request of the Indemnifying Party, use commercially reasonable
      efforts to cooperate in such defense; provided, that the Indemnifying Party shall bear the Indemnified Party&#8217;s reasonable out-of-pocket costs and expenses incurred in connection with such cooperation.&#160; So long as the Indemnifying Party is conducting
      the defense of such claim as provided in this Section 7.4, the Indemnified Party may retain separate co-counsel at its expense and may participate in the defense of such claim, and the Indemnifying Party may consent to the entry of any reasonable
      Judgment or enter into any reasonable settlement with respect to such claim [***].&#160; In the event the Indemnifying Party does not or ceases to conduct the defense of such claim as so provided, the Indemnified Party may defend against such claim and
      the Indemnified Party may consent to the entry of any reasonable Judgment or enter into any reasonable settlement with respect to such claim [***].&#160; Further, in the event the Indemnifying Party does not or ceases to conduct the defense of such claim
      as so provided, (A)&#160; subject to the limitations set forth in Section 7.3, the Indemnifying Party shall reimburse the Indemnified Party promptly and periodically for the reasonable out-of-pocket costs of defending against such claim, including
      reasonable attorneys&#8217; fees and expenses against reasonably detailed invoices, and (B) the Indemnifying Party shall remain responsible for any Losses the Indemnified Party may suffer as a result of such claim to the full extent provided in this
      Article 7. </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">46</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
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    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.5</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Exclusive Remedy</u>. Except as set forth in Section 9.10, from and after Closing, the rights of the parties hereto pursuant to (and subject to the
      conditions of) this Article 7 shall be the sole and exclusive remedy of the parties hereto and their respective Affiliates with respect to any claims (whether based in contract, tort or otherwise) resulting from or relating to any breach of the
      representations, warranties covenants and agreements made under this Agreement or any certificate, document or instrument delivered hereunder, and each party hereto hereby waives, to the fullest extent permitted under applicable law, and agrees not
      to assert after Closing, any other claim or action in respect of any such breach.&#160; Notwithstanding the foregoing, claims for common law fraud shall not be waived or limited in any way by this Article 7. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 7.6</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Tax Treatment for Indemnification Payments</u>. Any indemnification payments made pursuant to this Article 7 will be treated as an adjustment to the
      Purchase Price for U.S. federal income tax to the fullest extent permitted by applicable law. </div>
    <div>&#160;</div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 8</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">TERMINATION</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 8.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Mutual Termination</u>. This Agreement may be terminated at any time by mutual written agreement of the Buyer and the Seller. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 8.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Automatic Termination</u>. Unless earlier terminated as provided in Section 8.1, this Agreement shall continue in full force and effect until [***] days
      after such time as none of the Licensees ([***]) are obligated to make any payments to the Buyer in respect of any of the Purchased Royalty Payments, at which point this Agreement shall automatically terminate, except with respect to any rights that
      shall have accrued prior to such termination. Notwithstanding the foregoing, (A) the Buyer&#8217;s rights and Seller&#8217;s obligations under this Agreement with respect to Spinraza and BIIB-115, the 2012 Biogen License, the 2017 Biogen License and the Spinraza
      Upstream Licenses, Spinraza Licensed Patents, Spinraza Assigned Patents and BIIB-115 Licensed Patents shall terminate [***] days after such time as the Buyer has received Purchased SMA Royalty Payments in an amount equal to the SMA Royalty Cap, and
      (B) the Buyer&#8217;s rights and the Seller&#8217;s obligations under [***] shall terminate upon the Buyer&#8217;s receipt of Purchased Royalty Payments equal to [***] times the Purchase Price paid by the Buyer. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 8.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Survival</u>. Notwithstanding anything to the contrary in this Article 8, the following provisions shall survive termination of this Agreement: Section
      2.3 (True Sale), Section 5.1 (Disclosures), Section 5.2 (Payments Received in Error), Section 5.4 (Late Fee), Section 5.7 (Inspections and Audits of Licensee), Article 6 (Confidentiality), Article 7 (Indemnification), this Section 8.3 (Survival) and
      Article 9 (Miscellaneous). Termination of the Agreement shall not relieve any party of liability in respect of breaches under this Agreement by any party on or prior to termination. </div>
    <div style="text-indent: 72pt;"> <br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">47</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-align: center; color: rgb(1, 0, 0);">ARTICLE 9</div>
    <div style="text-align: center; color: rgb(1, 0, 0);"> <br>
    </div>
    <div style="text-align: center;">MISCELLANEOUS</div>
    <div style="text-align: center;"> <br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.1</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Notices</u>. All notices and other communications under this Agreement shall be in writing and shall be by email with PDF attachment, courier service or
      personal delivery to the following addresses, or to such other addresses as shall be designated from time to time by a party hereto in accordance with this Section 9.1: </div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">If to the Seller, to it at:</div>
    <div>&#160;</div>
    <div style="margin-left: 90pt;">Ionis Pharmaceuticals, Inc.</div>
    <div style="margin-left: 90pt;">2855 Gazelle Court</div>
    <div style="margin-left: 90pt;">Carlsbad, CA 92010</div>
    <div style="margin-left: 90pt;">Attention: General Counsel</div>
    <div style="margin-left: 90pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">With a copy to:</div>
    <div>&#160;</div>
    <div style="margin-left: 90pt;">Cooley LLP</div>
    <div style="margin-left: 90pt;">3 Embarcadero Center, 20<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</div>
    <div style="margin-left: 90pt;">San Francisco, CA 94111</div>
    <div style="margin-left: 90pt;">Attention: Gian-Michele a Marca and Alan Tamarelli</div>
    <div style="margin-left: 90pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">If to Akcea, to it at:</div>
    <div>&#160;</div>
    <div style="margin-left: 90pt;">Akcea Therapeutics, Inc.</div>
    <div style="margin-left: 90pt;">55 Cambridge Parkway</div>
    <div style="margin-left: 90pt;">Cambridge, MA 02142</div>
    <div style="margin-left: 90pt;">Attention: Chief Financial Officer</div>
    <div style="margin-left: 90pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">With a copy to:</div>
    <div>&#160;</div>
    <div style="margin-left: 90pt;">Cooley LLP</div>
    <div style="margin-left: 90pt;">3 Embarcadero Center, 20<sup style="vertical-align: text-top; line-height: 1; font-size: smaller;">th</sup> Floor</div>
    <div style="margin-left: 90pt;">San Francisco, CA 94111</div>
    <div style="margin-left: 90pt;">Attention: Gian-Michele a Marca and Alan Tamarelli</div>
    <div style="margin-left: 90pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="margin-left: 72pt;">If to the Buyer, to it at:</div>
    <div>&#160;</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">RP Management, LLC</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">110 E. 59th Street, Suite 3300</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">New York, New York 10022</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Attention: General Counsel</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Email: [***]</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">48</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="margin-right: 36pt; margin-left: 72pt;">With a copy to:</div>
    <div><br>
    </div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Goodwin Procter LLP</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">100 Northern Avenue</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Boston, Massachusetts 02210</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Attention: Jacqueline Mercier and</div>
    <div style="margin-right: 36pt; margin-left: 135pt;">Robert M. Crawford, Jr.</div>
    <div style="margin-right: 36pt; margin-left: 90pt;">Email:&#160; [***]</div>
    <div>&#160;</div>
    <div>All notices and communications under this Agreement shall be deemed to have been duly given (a) when delivered by hand, if personally delivered, (b) when received by a recipient, if sent by email, or (c) one Business Day following sending within
      the United States by overnight delivery via commercial one-day overnight courier service.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.2</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Expenses</u>. Except as otherwise provided herein, all fees, costs and expenses (including any legal, accounting and banking fees) incurred in connection
      with the preparation, negotiation, execution and delivery of this Agreement and to consummate the transactions contemplated hereby shall be paid by the party hereto incurring such fees, costs and expenses. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.3</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Assignment</u>. The provisions of this Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and
      permitted assigns. This Agreement, or any rights or obligations hereunder, may not be assigned by the Seller or Akcea without the prior written consent of the Buyer&#894; provided that each of the Seller and Akcea may assign this Agreement in its entirety
      to any Person that acquires all or substantially all of the Seller&#8217;s business or Akcea&#8217;s business, as applicable, to which this Agreement relates (including, for the avoidance of doubt, all of the Seller&#8217;s or Akcea&#8217;s (as applicable) right, title and
      interest in the Royalty Products, Upstream Licenses and License Agreements, and the Spinraza Licensed Patents, BIIB-115 Licensed Patents, and Pelacarsen Licensed Patents, as applicable), whether by merger, sale of assets or otherwise, so long as
      either such Person assumes all of the obligations of the Seller or Akcea, as applicable, in a writing delivered to the Buyer (in form and substance reasonably acceptable to the Buyer) within [***] Business Days of such closing in which such Person
      assumes all of the obligations of the Seller or Akcea to the Buyer under this Agreement; provided that if such Person is a Licensee, such Licensee shall, within [***] Business Days of closing, enter into an assumption agreement with, and reasonably
      acceptable to, the Buyer in which such Licensee assumes all of the obligations of the Seller or Akcea (as applicable) to the Buyer hereunder with respect to the applicable Royalty Products and agrees to pay the Purchased Royalty Payments directly to
      the Buyer notwithstanding any subsequent termination of the applicable License Agreement by the Licensee. This Agreement as a whole may not be assigned by the Buyer without the prior written consent of the Seller&#894; provided that the Buyer may assign
      its rights and obligations under this Agreement (a) to an Affiliate of the Buyer (provided that, if the Buyer is assigning any of its obligations to pay the Additional Purchase Price Payments the Buyer shall provide a guarantee of the payment of such
      Additional Purchase Price Payments in form and substance reasonably acceptable to the Seller) or (b) in its entirety to any third party that acquires all or substantially all the Buyer&#8217;s assets, whether by merger, sale of assets or otherwise,
      provided that (x) within [***] Business Days of closing any such transaction, the Buyer causes such assignee to deliver a writing to the Seller (in form and substance reasonably acceptable to the Seller) in which such Person assumes all of the
      obligations of the Buyer to the Seller under this Agreement.&#160; Notwithstanding the foregoing, the Buyer may assign its rights but not its obligations under this Agreement without the prior written consent of the Seller&#894; provided that the Buyer
      promptly notifies the Seller of such assignment. Any purported assignment in violation of this Section 9.3 shall be null and void. </div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">49</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.4</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Amendment and Waiver</u>. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;This Agreement may be amended, modified or supplemented only in a writing signed by each of the parties hereto. Any provision of this Agreement may be waived only in
      a writing signed by the parties hereto granting such waiver.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;No failure or delay on the part of any party hereto in exercising any right, power or remedy hereunder shall operate as a waiver thereof, nor shall any single or
      partial exercise of any such right, power or remedy preclude any other or further exercise thereof or the exercise of any other right, power or remedy. No course of dealing between the parties hereto shall be effective to amend, modify, supplement or
      waive any provision of this Agreement.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.5</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Entire Agreement</u>. This Agreement, the Exhibits annexed hereto and the Disclosure Schedule constitute the entire understanding between the parties
      hereto with respect to the subject matter hereof and supersede all other understandings and negotiations with respect thereto. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.6</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>No Third Party Beneficiaries</u>. This Agreement is for the sole benefit of the Seller, Akcea and the Buyer and their permitted successors and assigns and
      nothing herein expressed or implied shall give or be construed to give to any Person, other than the parties hereto and such successors and assigns, any legal or equitable rights hereunder; except that the Indemnified Parties shall be third party
      beneficiaries of the benefits provided for in Article 7. </div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.7</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Governing Law</u>. This Agreement shall be governed by, and construed in accordance with, the laws of the State of New York without giving effect to any
      choice or conflict of law provision or rule that would cause the application of the laws of any other jurisdiction. </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">50</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.8</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>JURISDICTION; VENUE</u>. </div>
      <div>&#160;</div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(a)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;EACH OF THE PARTIES HERETO HEREBY IRREVOCABLY AND UNCONDITIONALLY SUBMITS, FOR ITSELF AND ITS RESPECTIVE PROPERTY AND ASSETS, TO THE EXCLUSIVE JURISDICTION OF ANY
        NEW YORK STATE COURT OR FEDERAL COURT OF THE UNITED STATES OF AMERICA SITTING IN NEW YORK COUNTY, NEW YORK, AND ANY APPELLATE COURT THEREOF, IN ANY ACTION OR PROCEEDING ARISING OUT OF OR RELATING TO THIS AGREEMENT, OR FOR RECOGNITION OR ENFORCEMENT
        OF ANY JUDGMENT IN RESPECT THEREOF, AND THE BUYER AND THE SELLER HEREBY IRREVOCABLY AND UNCONDITIONALLY AGREE THAT ALL CLAIMS IN RESPECT OF ANY SUCH ACTION OR PROCEEDING MAY BE HEARD AND DETERMINED IN ANY SUCH NEW YORK STATE COURT OR, TO THE
        FULLEST EXTENT PERMITTED BY APPLICABLE LAW, IN SUCH FEDERAL COURT. THE BUYER AND THE SELLER HEREBY AGREE THAT A FINAL JUDGMENT IN ANY SUCH ACTION OR PROCEEDING SHALL BE CONCLUSIVE AND MAY BE ENFORCED IN OTHER JURISDICTIONS BY SUIT ON THE JUDGMENT
        OR IN ANY OTHER MANNER PROVIDED BY APPLICABLE LAW. EACH OF THE BUYER AND THE SELLER HEREBY SUBMITS TO THE EXCLUSIVE PERSONAL JURISDICTION AND VENUE OF SUCH NEW YORK STATE AND FEDERAL COURTS. THE BUYER AND THE SELLER AGREE, TO THE FULLEST EXTENT
        PERMITTED BY APPLICABLE LAW, THAT PROCESS MAY BE SERVED ON THE BUYER OR THE SELLER IN THE SAME MANNER THAT NOTICES MAY BE GIVEN PURSUANT TO SECTION 9.1 HEREOF.</div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);"> <br>
      </font></div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);"> <br>
      </font></div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(b)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;EACH OF THE PARTIES HERETO HEREBY IRREVOCABLY AND UNCONDITIONALLY WAIVES, TO THE FULLEST EXTENT IT MAY LEGALLY AND EFFECTIVELY DO SO, ANY OBJECTION THAT IT MAY NOW
      OR HEREAFTER HAVE TO THE LAYING OF VENUE OF ANY ACTION OR PROCEEDING ARISING OUT OF OR RELATING TO THIS AGREEMENT IN ANY NEW YORK STATE OR FEDERAL COURT. EACH OF THE BUYER AND THE SELLER HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY
      APPLICABLE LAW, THE DEFENSE OF AN INCONVENIENT FORUM TO THE MAINTENANCE OF SUCH ACTION OR PROCEEDING IN ANY SUCH COURT.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">(c)</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;EACH PARTY HEREBY JOINTLY AND SEVERALLY WAIVES ANY AND ALL RIGHT TO TRIAL BY JURY IN ANY ACTION OR PROCEEDING RELATING TO THIS AGREEMENT OR ANY OTHER DOCUMENT
      DELIVERED HEREUNDER OR IN CONNECTION HEREWITH, OR ANY TRANSACTION ARISING FROM OR CONNECTED TO ANY OF THE FOREGOING.&#160; EACH OF THE PARTIES REPRESENTS THAT THIS WAIVER IS KNOWINGLY, WILLINGLY, AND VOLUNTARILY GIVEN.</div>
    <div>&#160;</div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.9</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;<u>Severability</u>. If any term or provision of this Agreement shall for any reason be held to be invalid, illegal or unenforceable in any situation in any
      jurisdiction, then, to the extent that the economic and legal substance of the transactions contemplated hereby is not affected in a manner that is materially adverse to either party hereto, all other terms and provisions of this Agreement shall
      nevertheless remain in full force and effect and the enforceability and validity of the offending term or provision shall not be affected in any other situation or jurisdiction. </div>
    <div>&#160;</div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">51</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="border-width: 0px; clear: both; margin: 4px 0px; width: 100%; height: 2px; color: #000000; background-color: #000000;"></div>
    </div>
    <div>
      <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.10</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Specific Performance</u>. Each of the parties acknowledges and agrees that the other party would be damaged irreparably in the event any of the
        provisions of this Agreement are not performed in accordance with their specific terms or otherwise are breached or violated. Accordingly, notwithstanding Section 7.5, each of the parties agrees that, without posting bond or other undertaking, the
        other parties shall be entitled to an injunction or injunctions to prevent breaches or violations of the provisions of this Agreement and to enforce specifically this Agreement and the terms and provisions hereof in any action, suit or other
        proceeding instituted in any court of the United States or any state thereof having jurisdiction over the parties and the matter in addition to any other remedy to which it may be entitled, at law or in equity. Each party further agrees that, in
        the event of any action for specific performance in respect of such breach or violation, it shall not assert that the defense that a remedy at law would be adequate. </div>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);"> <br>
      </font></div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.11</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Counterparts</u>. This Agreement may be executed in any number of counterparts and by the parties hereto in separate counterparts, each of which when so
      executed shall be deemed to be an original and all of which taken together shall constitute one and the same agreement. Copies of executed counterparts transmitted by telecopy, facsimile or other similar means of electronic transmission, including
      &#8220;PDF,&#8221; shall be considered original executed counterparts, provided receipt of such counterparts is confirmed. </div>
    <div><br>
    </div>
    <div style="text-indent: 72pt;"><font style="color: rgb(1, 0, 0);">Section 9.12</font>&#160;&#160;&#160;&#160;&#160;&#160;&#160; <u>Relationships of the Parties</u>. The relationship between the Buyer and the Seller is solely that of purchaser and seller, and neither the Buyer nor the
      Seller has any fiduciary or other special relationship with the other party or any of its Affiliates.&#160; This Agreement is not a partnership or similar agreement, and nothing contained herein shall be deemed to constitute the Buyer and the Seller as a
      partnership, an association, a joint venture or any other kind of entity or legal form for any purposes, including any Tax purposes.&#160; The Buyer and the Seller agree that they shall not take any inconsistent position with respect to such treatment in
      a filing with any Governmental Entity. </div>
    <div>&#160;</div>
    <div style="text-align: center; font-style: italic;">[Signature Page Follows]</div>
    <div><br>
    </div>
    <div style="clear: both; margin-top: 10pt; margin-bottom: 10pt;" class="BRPFPageBreakArea">
      <div style="text-align: center;" class="BRPFPageNumberArea"><font style="font-size: 8pt; font-weight: normal; font-style: normal;" class="BRPFPageNumber">52</font></div>
      <div style="page-break-after: always;" class="BRPFPageBreak">
        <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
    </div>
    <div style="text-indent: 36pt;">IN WITNESS WHEREOF, the parties hereto have caused this Royalty Purchase Agreement to be executed and delivered by their respective representatives thereunto duly authorized as of the date first above written.</div>
    <div>&#160;</div>
    <table cellspacing="0" cellpadding="0" border="0" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;" id="z546e42d0923448d49d39f8fba0cb4749">

        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-indent: -6.55pt; margin-left: 6.55pt;">IONIS PHARMACEUTICALS, INC.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">
            <div>By:</div>
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          <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
            <div>
              <div>/s/Brett Monia</div>
            </div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">
            <div>Name: Brett Monia</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">
            <div>Title: Chief Executive Officer</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div style="text-indent: -6.55pt; margin-left: 6.55pt;">AKCEA THERAPEUTICS, INC.</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">&#160;</td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">
            <div>By:</div>
          </td>
          <td style="width: 42%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
            <div>
              <div>/s/Elizabeth Hougen</div>
            </div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">
            <div>Name: Elizabeth Hougen</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">
            <div>Title: Treasurer</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;" rowspan="1">&#160;</td>
          <td colspan="2" style="vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;" rowspan="1">&#160;</td>
          <td colspan="2" style="vertical-align: top;" rowspan="1">
            <div>(solely for the limited purposes set forth</div>
            <div>herein)</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;" rowspan="1">&#160;</td>
          <td colspan="2" style="vertical-align: top;" rowspan="1">&#160;</td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td colspan="2" style="vertical-align: top;">
            <div>ROYALTY PHARMA INVESTMENTS</div>
            <div>2019 ICAV</div>
          </td>
        </tr>
        <tr>
          <td style="width: 55%; vertical-align: top;">&#160;</td>
          <td style="width: 3%; vertical-align: top;">&#160;</td>
          <td style="width: 42%; vertical-align: top;">&#160;</td>
        </tr>
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  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif"><b>Exhibit 14</b></font></p>
  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; color: #A10067"><b>MESSAGE FROM THE CEO</b></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; color: #A10067">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">At Ionis, we dream big and are committed to bringing life-changing medicines to patients with unmet medical needs. With that goal comes a responsibility to behave ethically and conduct
    ourselves with integrity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Doing the right thing is not always easy. But we owe it to all stakeholders, especially patients, to make good decisions in a responsible manner. The Ionis Code of Ethics and Business
    Conduct (the &#8220;Code of Ethics&#8221;) is designed to help us achieve this objective. It describes the fundamental principles that guide us in all aspects of our business.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Of course, no code of conduct can cover all circumstances or anticipate every situation. For that reason, when faced with situations not addressed specifically by this Code of Ethics, we
    should apply our underlying principles and overall philosophy embedded within the Code of Ethics to the situation. We each have a responsibility to approach every situation ethically and with integrity.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">Thank you for your commitment to uphold the standards, principles and philosophy of this Code of Ethics. Together, we are a force for life.</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0">&#160;</p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-align: justify; color: Red">&#160;</p>
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        <td style="width: 80%">Chief Executive Officer</td>
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        <td style="padding-top: 0in; padding-left: 0in;"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>D.</b>&#160;&#160;&#160;<b>Commercializing Medicines</b></font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; color: #A10067; margin-top: 0; margin-bottom: 0; width: 100%">

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  <p style="color: #A10067; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table width="100%" cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; margin-top: 0pt; margin-bottom: 0pt">

      <tr style="vertical-align: top">
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; color: #EC7C30; margin-top: 0; margin-bottom: 0; width: 100%">

      <tr style="vertical-align: top; text-align: justify">
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        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>B.</b></font></td>
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      </tr>

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  <p style="color: #EC7C30; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: left">
        <td style="width: 50%; vertical-align: bottom;">&#160;</td>
        <td style="width: 50%; text-align: right; vertical-align: bottom">&#160;</td>
      </tr>

  </table>
  <div style="margin-bottom: 10pt; clear: both; margin-top: 10pt; margin-right: 0" class="BRPFPageBreakArea">
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  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
  <p style="margin-top: 0; margin-bottom: 0; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
  <table cellspacing="0" cellpadding="0" style="font: 10pt Times New Roman, Times, Serif; color: #A10067; margin-top: 0; margin-bottom: 0; width: 100%">

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      </tr>

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  <p style="color: #A10067; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 0.5in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: justify">
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        <td style="width: 0.5in; text-align: left"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt"><b>A.</b></font></td>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: justify">
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: justify">
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      </tr>

  </table>
  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top">
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      </tr>

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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: left">
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  </table>
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  <p style="margin: 0; text-align: right"><font style="font: 10pt Times New Roman, Times, Serif">&#160;</font></p>
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  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      </tr>

  </table>
  <p style="color: #EC7C30; font: 10pt Times New Roman, Times, Serif; margin: 0pt 0 0pt 0.5in; text-indent: 0in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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  <p style="margin-top: 0pt; margin-bottom: 0pt; font: 10pt Times New Roman, Times, Serif; margin-right: 0"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      <tr style="vertical-align: top; text-align: left">
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  <p style="margin-top: 0; margin-bottom: 0; text-align: center"><font style="font: 10pt Times New Roman, Times, Serif"><b>&#160;</b></font></p>
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      disciplinary action, up to and including termination. If necessary, Ionis may suspend your employment during an investigation into an alleged breach. Additional actions may include reassignment of work duties and limitation in future job
      opportunities. Ionis may refer violations of law to local or federal law enforcement authorities for possible prosecution.</font></p>
  <p style="font: 10pt Times New Roman, Times, Serif; margin: 0pt 0; text-indent: 1in"><font style="font-family: Times New Roman, Times, Serif; font-size: 10pt">&#160;</font></p>
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      </tr>

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<DOCUMENT>
<TYPE>EX-21.1
<SEQUENCE>16
<FILENAME>exhibit21-1.htm
<DESCRIPTION>EXHIBIT 21.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 23.1.2.5118
         Copyright 1995 - 2023 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; font-size: 10pt;"><div id="TRGRSegment:f499a0ae-02f9-48a9-add8-20f1dcaf844d"><div style="text-align: right; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Exhibit&#160;21.1</div><div style="text-align: right; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div><div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">LIST OF SUBSIDIARIES FOR THE REGISTRANT</div><div><br></div><div style="text-align: center; font-family: 'Times New Roman'; font-size: 10pt;">&#160;</div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics, Inc., a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics Canada Inc., a Canadian Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics France SAS, a French Company*</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics Germany GmbH, a German Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics UK Limited, a United Kingdom Limited Private Company</div><div><br></div><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Securities Corporation, a Massachusetts Corporation*</div><div><br></div><div style="text-align: left; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics Ireland Limited, an Irish Private Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Isis USA Limited, a United Kingdom Limited Private Company</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Osprey Therapeutics, Inc., a Delaware Corporation</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">PerIsis I Development Corporation, a Delaware Corporation**</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Symphony GenIsis,&#160;Inc., a Delaware Corporation**</div><div><br></div><div style="text-align: left; font-family: 'Times New Roman'; font-size: 10pt;">Ionis Development (Ireland) Limited, an Irish Private Company</div><div><br></div><div style="text-align: left;"><br></div><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="zff83014ad99d4f69acf83a7c3a2249a4"><tr><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">*</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman'; font-size: 10pt;">Akcea Therapeutics France SAS and <font style="font-size: 10pt; font-family: 'Times New Roman'; color: #000000;">Akcea Securities Corporation</font> were dissolved in December 2022.</div></td></tr></table><table style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;" class="DSPFListTable" cellpadding="0" cellspacing="0" id="z64990b15353d484295b3b241effe4388"><tr><td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman'; font-size: 10pt;">**</td><td style="width: auto; vertical-align: top; text-align: left;"><div style="font-family: 'Times New Roman'; font-size: 10pt;">PerIsis I Development Corporation and Symphony GenIsis,&#160;Inc. were dissolved in September 2021.</div></td></tr></table></div></body></html>
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<DOCUMENT>
<TYPE>EX-23.1
<SEQUENCE>17
<FILENAME>exhibit23-1.htm
<DESCRIPTION>EXHIBIT 23.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 23.1.2.5118
         Copyright 1995 - 2023 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; font-size: 10pt;"><div id="TRGRSegment:b8cd2a2a-2f7b-470b-8887-e5b31a337448"><div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Exhibit 23.1</div><div style="text-align: center;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> </font><br></div><div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM</div><div><br></div><div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consent to the incorporation by reference in the Registration Statements on Form S-3 (Nos. 333-71911, 333-90811, 333-38844, 333-71116, 333-71176, 333-89066, 333-89626, 333-128156, 333-130639, 333-134380, 333-141447, 333-151076, 333-188407, 333-217422 and 333-242382) and in the related Prospectuses, as applicable, and in the Registration Statements on Form S-8 (Nos. 333-05825, 333-55683, 333-40336, 333-59296, 333-91572, 333-106859, 333-116962, 333-125911, 333-133853, 333-142777, 333-151996, 333-160269, 333-168674, 333-176136, 333-184788, 333-190408, 333-207900, 333-219801, 333-233143, 333-242386, 333-251855, and 333-258503) of Ionis Pharmaceuticals, Inc. of our reports dated February 22, 2023, with respect to the consolidated financial statements of Ionis Pharmaceuticals, Inc. and the effectiveness of internal control over financial reporting of Ionis Pharmaceuticals, Inc. included in this Annual Report (Form 10-K) for the year ended December 31, 2022.</div><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br></div><table cellpadding="0" cellspacing="0" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;" id="z787065293e034871a01886e6ad16d4da"><tr><td style="width: 50.57%; vertical-align: top;">&#160;</td><td style="width: 49.43%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">/s/ ERNST &amp; YOUNG LLP</div></td></tr><tr><td style="width: 50.57%; vertical-align: top;">&#160;</td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 50.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">San Diego, California</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr><tr><td style="width: 50.57%; vertical-align: top;"><div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">February 22, 2023</div></td><td style="width: 49.43%; vertical-align: top;">&#160;</td></tr></table><div style="text-align: left;"><font style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </font><br></div></div></body></html>
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<DOCUMENT>
<TYPE>EX-31.1
<SEQUENCE>18
<FILENAME>exhibit31-1.htm
<DESCRIPTION>EXHIBIT 31.1
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 23.1.2.5118
         Copyright 1995 - 2023 Broadridge -->
  </head><body style="font-family: 'Times New Roman'; font-size: 10pt;"><div id="TRGRSegment:27688458-8a95-448c-9822-a3a5e0da6065"><div style="text-align: right; color: #000000; font-family: 'Times New Roman'; font-size: 10pt; font-weight: bold;">Exhibit 31.1</div><div><br></div><div style="text-align: center; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">CERTIFICATION</div><div><br></div><div style="text-align: justify; color: #000000; font-family: 'Times New Roman'; font-size: 10pt;">I, Brett P. 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<TYPE>EX-31.2
<SEQUENCE>19
<FILENAME>exhibit31-2.htm
<DESCRIPTION>EXHIBIT 31.2
<TEXT>
<html><head>
    <title>&nbsp;</title>
    <!-- Licensed to: Ionis Pharmaceuticals
         Document created using Broadridge PROfile 23.1.2.5118
         Copyright 1995 - 2023 Broadridge -->
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/EmploymentBenefits" id="EmploymentBenefits">
        <link:definition>060800 - Disclosure - Employment Benefits</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/LegalProceedings" id="LegalProceedings">
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/FourthQuarterFinancialDataUnaudited" id="FourthQuarterFinancialDataUnaudited">
        <link:definition>061000 - Disclosure - Fourth Quarter Financial Data (Unaudited)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:definition>080100 - Disclosure - Organization and Significant Accounting Policies (Tables)</link:definition>
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        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:definition>080500 - Disclosure - Stockholders' Equity (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/IncomeTaxesTables" id="IncomeTaxesTables">
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        <link:definition>080600 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/FourthQuarterFinancialDataUnauditedTables" id="FourthQuarterFinancialDataUnauditedTables">
        <!--Parent Role: Fourth Quarter Financial Data (Unaudited)-->
        <link:definition>081000 - Disclosure - Fourth Quarter Financial Data (Unaudited) (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:definition>090100 - Disclosure - Organization and Significant Accounting Policies, Basis of Presentation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090102 - Disclosure - Organization and Significant Accounting Policies, Revenue Recognition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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      <link:roleType roleURI="http://ionispharma.com/role/OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails" id="OrganizationAndSignificantAccountingPoliciesContractsReceivableDetails">
        <!--Parent Role: Organization and Significant Accounting Policies-->
        <link:definition>090104 - Disclosure - Organization and Significant Accounting Policies, Contracts Receivable (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <!--Parent Role: Organization and Significant Accounting Policies-->
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
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        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
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<DOCUMENT>
<TYPE>EX-101.LAB
<SEQUENCE>24
<FILENAME>ions-20221231_lab.xml
<DESCRIPTION>XBRL TAXONOMY EXTENSION LABEL LINKBASE
<TEXT>
<XBRL>
<?xml version="1.0" encoding="us-ascii"?>
<!--Generated by Broadridge PROfile 23.1.2.5118 Broadridge-->
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapitalMember" xlink:label="AdditionalPaidInCapitalMember" xlink:title="AdditionalPaidInCapitalMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdditionalPaidInCapitalCommonStock" xlink:label="AdditionalPaidInCapitalCommonStock" xlink:title="AdditionalPaidInCapitalCommonStock" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1" xml:lang="en-US" id="us-gaap_AdditionalPaidInCapitalCommonStock_lbl1">Additional Paid in Capital, Common Stock</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl" xml:lang="en-US" id="us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued_lbl">Issuance of warrants</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:label="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" xlink:title="AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Assets_lbl" xml:lang="en-US" id="us-gaap_Assets_lbl">Total assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl" xlink:title="label: Assets to us-gaap_Assets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Assets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Assets_lbl1" xml:lang="en-US" id="us-gaap_Assets_lbl1">Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Assets" xlink:to="us-gaap_Assets_lbl1" xlink:title="label: Assets to us-gaap_Assets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsCurrent" xlink:label="AssetsCurrent" xlink:title="AssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_AssetsCurrent_lbl" xml:lang="en-US" id="us-gaap_AssetsCurrent_lbl">Total current assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AssetsCurrent" xlink:to="us-gaap_AssetsCurrent_lbl" xlink:title="label: AssetsCurrent to us-gaap_AssetsCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrent_lbl1">Assets, Current</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AssetsCurrentAbstract" xlink:label="AssetsCurrentAbstract" xlink:title="AssetsCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_AssetsCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract_lbl">Current assets:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_AssetsCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_AssetsCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_AssetsCurrentAbstract_lbl1">Assets, Current [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:title="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract" xlink:to="us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" xlink:title="label: CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract to us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" xlink:title="label: CashCashEquivalentsAndShortTermInvestmentsAbstract to us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CashCashEquivalentsAndShortTermInvestmentsAbstract" xlink:to="us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" xlink:title="label: CashCashEquivalentsAndShortTermInvestmentsAbstract to us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockLineItems" xlink:to="us-gaap_ClassOfStockLineItems_lbl" xlink:title="label: ClassOfStockLineItems to us-gaap_ClassOfStockLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockLineItems_lbl1" xml:lang="en-US" id="us-gaap_ClassOfStockLineItems_lbl1">Class of Stock [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockLineItems" xlink:to="us-gaap_ClassOfStockLineItems_lbl1" xlink:title="label: ClassOfStockLineItems to us-gaap_ClassOfStockLineItems_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ClassOfStockDomain" xlink:label="ClassOfStockDomain" xlink:title="ClassOfStockDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockDomain_lbl" xml:lang="en-US" id="us-gaap_ClassOfStockDomain_lbl">Class of Stock [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockDomain" xlink:to="us-gaap_ClassOfStockDomain_lbl" xlink:title="label: ClassOfStockDomain to us-gaap_ClassOfStockDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockDisclosuresAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ClassOfStockDisclosuresAbstract_lbl" xml:lang="en-US" id="us-gaap_ClassOfStockDisclosuresAbstract_lbl">Share Repurchase Program [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockDisclosuresAbstract" xlink:to="us-gaap_ClassOfStockDisclosuresAbstract_lbl" xlink:title="label: ClassOfStockDisclosuresAbstract to us-gaap_ClassOfStockDisclosuresAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ClassOfStockDisclosuresAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ClassOfStockDisclosuresAbstract_lbl1" xml:lang="en-US" id="us-gaap_ClassOfStockDisclosuresAbstract_lbl1">Class of Stock Disclosures [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClassOfStockDisclosuresAbstract" xlink:to="us-gaap_ClassOfStockDisclosuresAbstract_lbl1" xlink:title="label: ClassOfStockDisclosuresAbstract to us-gaap_ClassOfStockDisclosuresAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:title="CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommitmentsAndContingenciesDisclosureAbstract" xlink:to="us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" xlink:title="label: CommitmentsAndContingenciesDisclosureAbstract to us-gaap_CommitmentsAndContingenciesDisclosureAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CommonStockMember" xlink:label="CommonStockMember" xlink:title="CommonStockMember" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1" xml:lang="en-US" id="us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_lbl1">Common Stock, Capital Shares Reserved for Future Issuance</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidationPolicyTextBlock" xlink:to="us-gaap_ConsolidationPolicyTextBlock_lbl1" xlink:title="label: ConsolidationPolicyTextBlock to us-gaap_ConsolidationPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityCurrent" xlink:label="ContractWithCustomerLiabilityCurrent" xlink:title="ContractWithCustomerLiabilityCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl">Current portion of deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1">Contract with Customer, Liability, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityCurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityCurrent to us-gaap_ContractWithCustomerLiabilityCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetNetCurrentAbstract" xlink:label="ContractWithCustomerAssetNetCurrentAbstract" xlink:title="ContractWithCustomerAssetNetCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrentAbstract" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl" xlink:title="label: ContractWithCustomerAssetNetCurrentAbstract to us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl1">Contract with Customer, Asset, after Allowance for Credit Loss, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrentAbstract" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl1" xlink:title="label: ContractWithCustomerAssetNetCurrentAbstract to us-gaap_ContractWithCustomerAssetNetCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityAbstract" xlink:label="ContractWithCustomerLiabilityAbstract" xlink:title="ContractWithCustomerLiabilityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl">Deferred Revenue [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1">Contract with Customer, Liability [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityAbstract" xlink:to="us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" xlink:title="label: ContractWithCustomerLiabilityAbstract to us-gaap_ContractWithCustomerLiabilityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiability" xlink:label="ContractWithCustomerLiability" xlink:title="ContractWithCustomerLiability" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiability_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl">Deferred revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiability_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiability_lbl1">Contract with Customer, Liability</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiability" xlink:to="us-gaap_ContractWithCustomerLiability_lbl1" xlink:title="label: ContractWithCustomerLiability to us-gaap_ContractWithCustomerLiability_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerAssetNetCurrent" xlink:label="ContractWithCustomerAssetNetCurrent" xlink:title="ContractWithCustomerAssetNetCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl">Contracts receivable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1">Contract with Customer, Asset, after Allowance for Credit Loss, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerAssetNetCurrent" xlink:to="us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" xlink:title="label: ContractWithCustomerAssetNetCurrent to us-gaap_ContractWithCustomerAssetNetCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent" xlink:label="ContractWithCustomerLiabilityNoncurrent" xlink:title="ContractWithCustomerLiabilityNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl">Long-term deferred contract revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1">Contract with Customer, Liability, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityNoncurrent" xlink:to="us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" xlink:title="label: ContractWithCustomerLiabilityNoncurrent to us-gaap_ContractWithCustomerLiabilityNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractWithCustomerLiabilityRevenueRecognized" xlink:label="ContractWithCustomerLiabilityRevenueRecognized" xlink:title="ContractWithCustomerLiabilityRevenueRecognized" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl">Revenue recognized from amounts in beginning deferred revenue balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xml:lang="en-US" id="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1">Contract with Customer, Liability, Revenue Recognized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractWithCustomerLiabilityRevenueRecognized" xlink:to="us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" xlink:title="label: ContractWithCustomerLiabilityRevenueRecognized to us-gaap_ContractWithCustomerLiabilityRevenueRecognized_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ContractReceivablesAbstract" xlink:label="ContractReceivablesAbstract" xlink:title="ContractReceivablesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ContractReceivablesAbstract_lbl" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ContractReceivablesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ContractReceivablesAbstract_lbl1" xml:lang="en-US" id="us-gaap_ContractReceivablesAbstract_lbl1">Contracts Receivable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ContractReceivablesAbstract" xlink:to="us-gaap_ContractReceivablesAbstract_lbl1" xlink:title="label: ContractReceivablesAbstract to us-gaap_ContractReceivablesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleDebt" xlink:label="ConvertibleDebt" xlink:title="ConvertibleDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebt_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebt_lbl">Convertible senior notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt_lbl" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebt_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebt_lbl1">Convertible Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebt" xlink:to="us-gaap_ConvertibleDebt_lbl1" xlink:title="label: ConvertibleDebt to us-gaap_ConvertibleDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleDebtNoncurrent" xlink:label="ConvertibleDebtNoncurrent" xlink:title="ConvertibleDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl">Convertible senior notes, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtNoncurrent_lbl1">Convertible Debt, Noncurrent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtNoncurrent" xlink:to="us-gaap_ConvertibleDebtNoncurrent_lbl1" xlink:title="label: ConvertibleDebtNoncurrent to us-gaap_ConvertibleDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:label="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:title="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1">Convertible Notes Payable [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract" xlink:to="us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" xlink:title="label: ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract to us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ConvertibleDebtTableTextBlock" xlink:label="ConvertibleDebtTableTextBlock" xlink:title="ConvertibleDebtTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl">Convertible Senior Notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_ConvertibleDebtTableTextBlock_lbl1">Convertible Debt [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleDebtTableTextBlock" xlink:to="us-gaap_ConvertibleDebtTableTextBlock_lbl1" xlink:title="label: ConvertibleDebtTableTextBlock to us-gaap_ConvertibleDebtTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="CorporateDebtSecuritiesMember" xlink:title="CorporateDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CorporateDebtSecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_CorporateDebtSecuritiesMember_lbl1">Corporate Debt Securities [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CorporateDebtSecuritiesMember" xlink:to="us-gaap_CorporateDebtSecuritiesMember_lbl1" xlink:title="label: CorporateDebtSecuritiesMember to us-gaap_CorporateDebtSecuritiesMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfGoodsAndServicesSold" xlink:label="CostOfGoodsAndServicesSold" xlink:title="CostOfGoodsAndServicesSold" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl">Cost of sales</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfGoodsAndServicesSold_lbl1" xml:lang="en-US" id="us-gaap_CostOfGoodsAndServicesSold_lbl1">Cost of Goods and Services Sold</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostOfGoodsAndServicesSold" xlink:to="us-gaap_CostOfGoodsAndServicesSold_lbl1" xlink:title="label: CostOfGoodsAndServicesSold to us-gaap_CostOfGoodsAndServicesSold_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostOfSalesPolicyTextBlock" xlink:label="CostOfSalesPolicyTextBlock" xlink:title="CostOfSalesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesPolicyTextBlock_lbl">Cost of Sales</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostOfSalesMember_lbl" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl">Cost of Sales [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CostOfSalesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostOfSalesMember_lbl1" xml:lang="en-US" id="us-gaap_CostOfSalesMember_lbl1">Cost of Sales [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpensesAbstract" xlink:label="CostsAndExpensesAbstract" xlink:title="CostsAndExpensesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl">Expenses:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpensesAbstract_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpensesAbstract_lbl1">Costs and Expenses [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpensesAbstract" xlink:to="us-gaap_CostsAndExpensesAbstract_lbl1" xlink:title="label: CostsAndExpensesAbstract to us-gaap_CostsAndExpensesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CostsAndExpenses" xlink:label="CostsAndExpenses" xlink:title="CostsAndExpenses" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CostsAndExpenses_lbl" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl">Total operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CostsAndExpenses_lbl1" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl1">Operating expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl1" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CostsAndExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CostsAndExpenses_lbl2" xml:lang="en-US" id="us-gaap_CostsAndExpenses_lbl2">Costs and Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CostsAndExpenses" xlink:to="us-gaap_CostsAndExpenses_lbl2" xlink:title="label: CostsAndExpenses to us-gaap_CostsAndExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CreditConcentrationRiskMember" xlink:label="CreditConcentrationRiskMember" xlink:title="CreditConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CreditConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CreditConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CreditConcentrationRiskMember_lbl">Credit Concentration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CreditConcentrationRiskMember" xlink:to="us-gaap_CreditConcentrationRiskMember_lbl" xlink:title="label: CreditConcentrationRiskMember to us-gaap_CreditConcentrationRiskMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:label="CurrentStateAndLocalTaxExpenseBenefit" xlink:title="CurrentStateAndLocalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl">State</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentStateAndLocalTaxExpenseBenefit" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl" xlink:title="label: CurrentStateAndLocalTaxExpenseBenefit to us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1">Current State and Local Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentStateAndLocalTaxExpenseBenefit" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" xlink:title="label: CurrentStateAndLocalTaxExpenseBenefit to us-gaap_CurrentStateAndLocalTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CurrentFederalTaxExpenseBenefit" xlink:label="CurrentFederalTaxExpenseBenefit" xlink:title="CurrentFederalTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentFederalTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentFederalTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_CurrentFederalTaxExpenseBenefit_lbl">Federal</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFederalTaxExpenseBenefit" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit_lbl" xlink:title="label: CurrentFederalTaxExpenseBenefit to us-gaap_CurrentFederalTaxExpenseBenefit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1">Current Federal Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFederalTaxExpenseBenefit" xlink:to="us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" xlink:title="label: CurrentFederalTaxExpenseBenefit to us-gaap_CurrentFederalTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CurrentForeignTaxExpenseBenefit" xlink:label="CurrentForeignTaxExpenseBenefit" xlink:title="CurrentForeignTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentForeignTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentForeignTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_CurrentForeignTaxExpenseBenefit_lbl">Foreign</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentForeignTaxExpenseBenefit" xlink:to="us-gaap_CurrentForeignTaxExpenseBenefit_lbl" xlink:title="label: CurrentForeignTaxExpenseBenefit to us-gaap_CurrentForeignTaxExpenseBenefit_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit" xlink:label="CurrentIncomeTaxExpenseBenefit" xlink:title="CurrentIncomeTaxExpenseBenefit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl">Total current income tax expense (benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl" xlink:title="label: CurrentIncomeTaxExpenseBenefit to us-gaap_CurrentIncomeTaxExpenseBenefit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1">Current Income Tax Expense (Benefit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefit" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" xlink:title="label: CurrentIncomeTaxExpenseBenefit to us-gaap_CurrentIncomeTaxExpenseBenefit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:label="CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:title="CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl">Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract" xlink:to="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl" xlink:title="label: CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract to us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1" xml:lang="en-US" id="us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract_lbl1">Current Income Tax Expense (Benefit), Continuing Operations [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_CustomerConcentrationRiskMember" xlink:label="CustomerConcentrationRiskMember" xlink:title="CustomerConcentrationRiskMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl">Strategic Partner [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_CustomerConcentrationRiskMember_lbl1" xml:lang="en-US" id="us-gaap_CustomerConcentrationRiskMember_lbl1">Customer Concentration Risk [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CustomerConcentrationRiskMember" xlink:to="us-gaap_CustomerConcentrationRiskMember_lbl1" xlink:title="label: CustomerConcentrationRiskMember to us-gaap_CustomerConcentrationRiskMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueLineItems" xlink:label="DisaggregationOfRevenueLineItems" xlink:title="DisaggregationOfRevenueLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueLineItems_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueLineItems_lbl">Disaggregation of Revenue [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DisaggregationOfRevenueTable" xlink:label="DisaggregationOfRevenueTable" xlink:title="DisaggregationOfRevenueTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DisaggregationOfRevenueTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DisaggregationOfRevenueTable_lbl" xml:lang="en-US" id="us-gaap_DisaggregationOfRevenueTable_lbl">Disaggregation of Revenue [Table]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:label="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" xlink:title="DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedTotalLabel" xlink:title="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl" xml:lang="en-US" id="us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_lbl">Total temporary impairment</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1" xml:lang="en-US" id="us-gaap_DebtInstrumentInterestRateStatedPercentage_lbl1">Interest rate on convertible senior notes</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_DeferredTaxLiabilitiesLeasingArrangements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_DeferredTaxLiabilitiesLeasingArrangements_lbl1" xml:lang="en-US" id="us-gaap_DeferredTaxLiabilitiesLeasingArrangements_lbl1">Deferred Tax Liabilities, Leasing Arrangements</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_DerivativesPolicyTextBlock" xlink:label="DerivativesPolicyTextBlock" xlink:title="DerivativesPolicyTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EffectiveIncomeTaxRateReconciliationTaxCredits" xlink:to="us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits_lbl1" xlink:title="label: EffectiveIncomeTaxRateReconciliationTaxCredits to us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockOptionMember" xlink:label="EmployeeStockOptionMember" xlink:title="EmployeeStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockOptionMember_lbl" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl">Employee Stock Options [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_EmployeeStockOptionMember_lbl1" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl1">Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl1" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockOptionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeStockOptionMember_lbl2" xml:lang="en-US" id="us-gaap_EmployeeStockOptionMember_lbl2">Share-Based Payment Arrangement, Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockOptionMember" xlink:to="us-gaap_EmployeeStockOptionMember_lbl2" xlink:title="label: EmployeeStockOptionMember to us-gaap_EmployeeStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:title="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl">Share-based Compensation Arrangement by Share-based Payment Award, Compensation Cost [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems to us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl">Unrecognized compensation cost related to non-vested units</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1" xml:lang="en-US" id="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl1">Weighted average period for recognition</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1 to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeStockMember" xlink:label="EmployeeStockMember" xlink:title="EmployeeStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_EmployeeStockMember_lbl" xml:lang="en-US" id="us-gaap_EmployeeStockMember_lbl">ESPP [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockMember" xlink:to="us-gaap_EmployeeStockMember_lbl" xlink:title="label: EmployeeStockMember to us-gaap_EmployeeStockMember_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:label="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:title="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions" xlink:to="us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" xlink:title="label: EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions to us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_EmployeeRelatedLiabilitiesCurrent" xlink:label="EmployeeRelatedLiabilitiesCurrent" xlink:title="EmployeeRelatedLiabilitiesCurrent" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1">Employee-related Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeRelatedLiabilitiesCurrent" xlink:to="us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" xlink:title="label: EmployeeRelatedLiabilitiesCurrent to us-gaap_EmployeeRelatedLiabilitiesCurrent_lbl1" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract" xlink:label="GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract" xlink:title="GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:label="IncomeTaxReconciliationPriorYearIncomeTaxes" xlink:title="IncomeTaxReconciliationPriorYearIncomeTaxes" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInAccountsPayable_lbl1">Increase (Decrease) in Accounts Payable</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInInventories" xlink:to="us-gaap_IncreaseDecreaseInInventories_lbl1" xlink:title="label: IncreaseDecreaseInInventories to us-gaap_IncreaseDecreaseInInventories_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1">Increase (Decrease) in Other Operating Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherOperatingAssets" xlink:to="us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" xlink:title="label: IncreaseDecreaseInOtherOperatingAssets to us-gaap_IncreaseDecreaseInOtherOperatingAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOperatingCapitalAbstract" xlink:label="IncreaseDecreaseInOperatingCapitalAbstract" xlink:title="IncreaseDecreaseInOperatingCapitalAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl">Changes in operating assets and liabilities:</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1">Increase (Decrease) in Operating Capital [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOperatingCapitalAbstract" xlink:to="us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" xlink:title="label: IncreaseDecreaseInOperatingCapitalAbstract to us-gaap_IncreaseDecreaseInOperatingCapitalAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:label="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:title="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl">Accrued compensation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1">Increase (Decrease) in Other Employee-Related Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherEmployeeRelatedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" xlink:title="label: IncreaseDecreaseInOtherEmployeeRelatedLiabilities to us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" xlink:label="IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" xlink:title="IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl">Accrued liabilities and other current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities" xlink:to="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl" xlink:title="label: IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities to us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities_lbl1">Increase (Decrease) in Other Accounts Payable and Accrued Liabilities</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward" xlink:label="IncreaseDecreaseInStockholdersEquityRollForward" xlink:title="IncreaseDecreaseInStockholdersEquityRollForward" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xml:lang="en-US" id="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1">Increase (Decrease) in Stockholders' Equity [Roll Forward]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInStockholdersEquityRollForward" xlink:to="us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" xlink:title="label: IncreaseDecreaseInStockholdersEquityRollForward to us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:label="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" xlink:title="IncrementalCommonSharesAttributableToShareBasedPaymentArrangements" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl" xml:lang="en-US" id="us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_lbl">Shares issuable related to stock-based compensation (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities" xlink:label="IncrementalCommonSharesAttributableToConversionOfDebtSecurities" xlink:title="IncrementalCommonSharesAttributableToConversionOfDebtSecurities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_lbl" xml:lang="en-US" id="us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_lbl">Shares issuable related to our convertible notes (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPayableCurrentAndNoncurrent" xlink:label="InterestPayableCurrentAndNoncurrent" xlink:title="InterestPayableCurrentAndNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPayableCurrentAndNoncurrent_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_InterestPayableCurrentAndNoncurrent_lbl" xml:lang="en-US" id="us-gaap_InterestPayableCurrentAndNoncurrent_lbl">Less: Fixed and determinable interest</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1">Interest Payable</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPayableCurrentAndNoncurrent" xlink:to="us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" xlink:title="label: InterestPayableCurrentAndNoncurrent to us-gaap_InterestPayableCurrentAndNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestExpense" xlink:label="InterestExpense" xlink:title="InterestExpense" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_InterestExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestExpense_lbl1" xml:lang="en-US" id="us-gaap_InterestExpense_lbl1">Interest Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestExpense" xlink:to="us-gaap_InterestExpense_lbl1" xlink:title="label: InterestExpense to us-gaap_InterestExpense_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InterestPaidNet" xlink:label="InterestPaidNet" xlink:title="InterestPaidNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InterestPaidNet_lbl" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl">Interest paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InterestPaidNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InterestPaidNet_lbl1" xml:lang="en-US" id="us-gaap_InterestPaidNet_lbl1">Interest Paid, Excluding Capitalized Interest, Operating Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InterestPaidNet" xlink:to="us-gaap_InterestPaidNet_lbl1" xlink:title="label: InterestPaidNet to us-gaap_InterestPaidNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InternalRevenueServiceIRSMember" xlink:label="InternalRevenueServiceIRSMember" xlink:title="InternalRevenueServiceIRSMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InternalRevenueServiceIRSMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InternalRevenueServiceIRSMember_lbl" xml:lang="en-US" id="us-gaap_InternalRevenueServiceIRSMember_lbl">Federal [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InternalRevenueServiceIRSMember" xlink:to="us-gaap_InternalRevenueServiceIRSMember_lbl" xlink:title="label: InternalRevenueServiceIRSMember to us-gaap_InternalRevenueServiceIRSMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryLineItems" xlink:label="InventoryLineItems" xlink:title="InventoryLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryLineItems_lbl" xml:lang="en-US" id="us-gaap_InventoryLineItems_lbl">Inventory [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryLineItems" xlink:to="us-gaap_InventoryLineItems_lbl" xlink:title="label: InventoryLineItems to us-gaap_InventoryLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryCurrentTable" xlink:label="InventoryCurrentTable" xlink:title="InventoryCurrentTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryCurrentTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryCurrentTable_lbl" xml:lang="en-US" id="us-gaap_InventoryCurrentTable_lbl">Inventory, Current [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryCurrentTable" xlink:to="us-gaap_InventoryCurrentTable_lbl" xlink:title="label: InventoryCurrentTable to us-gaap_InventoryCurrentTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryFinishedGoods" xlink:label="InventoryFinishedGoods" xlink:title="InventoryFinishedGoods" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryFinishedGoods_lbl" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl">Finished goods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryFinishedGoods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryFinishedGoods_lbl1" xml:lang="en-US" id="us-gaap_InventoryFinishedGoods_lbl1">Inventory, Finished Goods, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryFinishedGoods" xlink:to="us-gaap_InventoryFinishedGoods_lbl1" xlink:title="label: InventoryFinishedGoods to us-gaap_InventoryFinishedGoods_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryPolicyTextBlock" xlink:label="InventoryPolicyTextBlock" xlink:title="InventoryPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InventoryPolicyTextBlock_lbl1">Inventory, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryPolicyTextBlock" xlink:to="us-gaap_InventoryPolicyTextBlock_lbl1" xlink:title="label: InventoryPolicyTextBlock to us-gaap_InventoryPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNet" xlink:label="InventoryNet" xlink:title="InventoryNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNet_lbl" xml:lang="en-US" id="us-gaap_InventoryNet_lbl">Inventories</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_InventoryNet_lbl1" xml:lang="en-US" id="us-gaap_InventoryNet_lbl1">Total inventory</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl1" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNet_lbl2" xml:lang="en-US" id="us-gaap_InventoryNet_lbl2">Inventory, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNet" xlink:to="us-gaap_InventoryNet_lbl2" xlink:title="label: InventoryNet to us-gaap_InventoryNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryNetAbstract" xlink:label="InventoryNetAbstract" xlink:title="InventoryNetAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryNetAbstract_lbl" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl">Inventory [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryNetAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryNetAbstract_lbl1" xml:lang="en-US" id="us-gaap_InventoryNetAbstract_lbl1">Inventory, Net [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryNetAbstract" xlink:to="us-gaap_InventoryNetAbstract_lbl1" xlink:title="label: InventoryNetAbstract to us-gaap_InventoryNetAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryRawMaterials" xlink:label="InventoryRawMaterials" xlink:title="InventoryRawMaterials" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryRawMaterials_lbl" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl">Raw materials</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryRawMaterials_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryRawMaterials_lbl1" xml:lang="en-US" id="us-gaap_InventoryRawMaterials_lbl1">Inventory, Raw Materials, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryRawMaterials" xlink:to="us-gaap_InventoryRawMaterials_lbl1" xlink:title="label: InventoryRawMaterials to us-gaap_InventoryRawMaterials_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InventoryWorkInProcess" xlink:label="InventoryWorkInProcess" xlink:title="InventoryWorkInProcess" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InventoryWorkInProcess_lbl" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl">Work in process</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InventoryWorkInProcess_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InventoryWorkInProcess_lbl1" xml:lang="en-US" id="us-gaap_InventoryWorkInProcess_lbl1">Inventory, Work in Process, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InventoryWorkInProcess" xlink:to="us-gaap_InventoryWorkInProcess_lbl1" xlink:title="label: InventoryWorkInProcess to us-gaap_InventoryWorkInProcess_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentTextBlock" xlink:label="InvestmentTextBlock" xlink:title="InvestmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentTextBlock_lbl">Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentTextBlock" xlink:to="us-gaap_InvestmentTextBlock_lbl" xlink:title="label: InvestmentTextBlock to us-gaap_InvestmentTextBlock_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentHoldingsLineItems" xlink:label="InvestmentHoldingsLineItems" xlink:title="InvestmentHoldingsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsLineItems_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsLineItems_lbl">Investment Holdings [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsLineItems" xlink:to="us-gaap_InvestmentHoldingsLineItems_lbl" xlink:title="label: InvestmentHoldingsLineItems to us-gaap_InvestmentHoldingsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentPolicyTextBlock" xlink:label="InvestmentPolicyTextBlock" xlink:title="InvestmentPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl">Cash, Cash Equivalents and Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentPolicyTextBlock_lbl1">Investment, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentPolicyTextBlock" xlink:to="us-gaap_InvestmentPolicyTextBlock_lbl1" xlink:title="label: InvestmentPolicyTextBlock to us-gaap_InvestmentPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentIncomeNet" xlink:label="InvestmentIncomeNet" xlink:title="InvestmentIncomeNet" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentIncomeNet_lbl" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl">Investment income</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentIncomeNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentIncomeNet_lbl1" xml:lang="en-US" id="us-gaap_InvestmentIncomeNet_lbl1">Investment Income, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentIncomeNet" xlink:to="us-gaap_InvestmentIncomeNet_lbl1" xlink:title="label: InvestmentIncomeNet to us-gaap_InvestmentIncomeNet_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentHoldingsTable" xlink:label="InvestmentHoldingsTable" xlink:title="InvestmentHoldingsTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentHoldingsTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentHoldingsTable_lbl" xml:lang="en-US" id="us-gaap_InvestmentHoldingsTable_lbl">Investment Holdings [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentHoldingsTable" xlink:to="us-gaap_InvestmentHoldingsTable_lbl" xlink:title="label: InvestmentHoldingsTable to us-gaap_InvestmentHoldingsTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract" xlink:label="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:title="InvestmentsDebtAndEquitySecuritiesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl">Available-for-sale and Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:to="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" xlink:title="label: InvestmentsDebtAndEquitySecuritiesAbstract to us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1">Investments, Debt and Equity Securities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsDebtAndEquitySecuritiesAbstract" xlink:to="us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" xlink:title="label: InvestmentsDebtAndEquitySecuritiesAbstract to us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsAbstract" xlink:label="InvestmentsAbstract" xlink:title="InvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAbstract_lbl">Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAbstract" xlink:to="us-gaap_InvestmentsAbstract_lbl" xlink:title="label: InvestmentsAbstract to us-gaap_InvestmentsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:label="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:title="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl">Contract Maturity of Available-for-Sale Securities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1">Investments Classified by Contractual Maturity Date [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsClassifiedByContractualMaturityDateTableTextBlock" xlink:to="us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" xlink:title="label: InvestmentsClassifiedByContractualMaturityDateTableTextBlock to us-gaap_InvestmentsClassifiedByContractualMaturityDateTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_InvestmentsAllOtherInvestmentsAbstract" xlink:label="InvestmentsAllOtherInvestmentsAbstract" xlink:title="InvestmentsAllOtherInvestmentsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl">Ownership Interests in Private and Public Companies [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xml:lang="en-US" id="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1">Investments, All Other Investments [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentsAllOtherInvestmentsAbstract" xlink:to="us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" xlink:title="label: InvestmentsAllOtherInvestmentsAbstract to us-gaap_InvestmentsAllOtherInvestmentsAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LessorOperatingLeaseTermOfContract" xlink:label="LessorOperatingLeaseTermOfContract" xlink:title="LessorOperatingLeaseTermOfContract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeaseTermOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LessorOperatingLeaseTermOfContract_lbl" xml:lang="en-US" id="us-gaap_LessorOperatingLeaseTermOfContract_lbl">Term of sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseTermOfContract" xlink:to="us-gaap_LessorOperatingLeaseTermOfContract_lbl" xlink:title="label: LessorOperatingLeaseTermOfContract to us-gaap_LessorOperatingLeaseTermOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeaseTermOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LessorOperatingLeaseTermOfContract_lbl1" xml:lang="en-US" id="us-gaap_LessorOperatingLeaseTermOfContract_lbl1">Lessor, Operating Lease, Term of Contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeaseTermOfContract" xlink:to="us-gaap_LessorOperatingLeaseTermOfContract_lbl1" xlink:title="label: LessorOperatingLeaseTermOfContract to us-gaap_LessorOperatingLeaseTermOfContract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LessorOperatingLeasePaymentsToBeReceived" xlink:label="LessorOperatingLeasePaymentsToBeReceived" xlink:title="LessorOperatingLeasePaymentsToBeReceived" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePaymentsToBeReceived" xlink:to="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" xlink:title="label: LessorOperatingLeasePaymentsToBeReceived to us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1" xml:lang="en-US" id="us-gaap_LessorOperatingLeasePaymentsToBeReceived_lbl1">Lessor, Operating Lease, Payments to be Received</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl">Long-Term Obligations and Commitments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock_lbl" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeasesTextBlock_lbl1">Lessee, Operating Leases [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasesTextBlock" xlink:to="us-gaap_LesseeOperatingLeasesTextBlock_lbl1" xlink:title="label: LesseeOperatingLeasesTextBlock to us-gaap_LesseeOperatingLeasesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeasesPolicyTextBlock" xlink:label="LesseeLeasesPolicyTextBlock" xlink:title="LesseeLeasesPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl">Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeLeasesPolicyTextBlock_lbl1">Lessee, Leases [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeasesPolicyTextBlock" xlink:to="us-gaap_LesseeLeasesPolicyTextBlock_lbl1" xlink:title="label: LesseeLeasesPolicyTextBlock to us-gaap_LesseeLeasesPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl">2027</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1">Lessee, Operating Lease, Liability, to be Paid, Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl">Thereafter</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1">Lessee, Operating Lease, Liability, to be Paid, after Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl">2024</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1">Lessee, Operating Lease, Liability, to be Paid, Year Two</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearTwo" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearTwo to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm" xlink:label="LesseeOperatingLeaseRenewalTerm" xlink:title="LesseeOperatingLeaseRenewalTerm" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl">Term of lease extension</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1">Lessee, Operating Lease, Renewal Term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseRenewalTerm" xlink:to="us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" xlink:title="label: LesseeOperatingLeaseRenewalTerm to us-gaap_LesseeOperatingLeaseRenewalTerm_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseTermOfContract" xlink:label="LesseeOperatingLeaseTermOfContract" xlink:title="LesseeOperatingLeaseTermOfContract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl">Initial term of operating lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseTermOfContract" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract_lbl" xlink:title="label: LesseeOperatingLeaseTermOfContract to us-gaap_LesseeOperatingLeaseTermOfContract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1">Lessee, Operating Lease, Term of Contract</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseTermOfContract" xlink:to="us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" xlink:title="label: LesseeOperatingLeaseTermOfContract to us-gaap_LesseeOperatingLeaseTermOfContract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl">2026</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFour to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1">Lessee, Operating Lease, Liability, to be Paid, Year Four</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearFour" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearFour to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl">2023</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1">Lessee, Operating Lease, Liability, to be Paid, Year One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl">2025</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1">Lessee, Operating Lease, Liability, to be Paid, Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDueYearThree" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDueYearThree to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:label="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:title="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl">Less: Imputed interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityUndiscountedExcessAmount to us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1">Lessee, Operating Lease, Liability, Undiscounted Excess Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityUndiscountedExcessAmount" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityUndiscountedExcessAmount to us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeaseDescriptionTable" xlink:label="LesseeLeaseDescriptionTable" xlink:title="LesseeLeaseDescriptionTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionTable_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionTable_lbl">Lessee, Lease, Description [Table]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:label="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:title="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1">Lessee, Operating Lease, Liability, Maturity [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityMaturityTableTextBlock" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityMaturityTableTextBlock to us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeDisclosureAbstract" xlink:label="LesseeDisclosureAbstract" xlink:title="LesseeDisclosureAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl">Operating Leases [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeDisclosureAbstract_lbl1" xml:lang="en-US" id="us-gaap_LesseeDisclosureAbstract_lbl1">Lessee Disclosure [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeDisclosureAbstract" xlink:to="us-gaap_LesseeDisclosureAbstract_lbl1" xlink:title="label: LesseeDisclosureAbstract to us-gaap_LesseeDisclosureAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeLeaseDescriptionLineItems" xlink:label="LesseeLeaseDescriptionLineItems" xlink:title="LesseeLeaseDescriptionLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xml:lang="en-US" id="us-gaap_LesseeLeaseDescriptionLineItems_lbl">Lessee, Lease, Description [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeLeaseDescriptionLineItems" xlink:to="us-gaap_LesseeLeaseDescriptionLineItems_lbl" xlink:title="label: LesseeLeaseDescriptionLineItems to us-gaap_LesseeLeaseDescriptionLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue" xlink:label="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:title="LesseeOperatingLeaseLiabilityPaymentsDue" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl">Lease payments to be made over initial term of lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1">Total minimum lease payments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl2" xml:lang="en-US" id="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl2">Lessee, Operating Lease, Liability, to be Paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseLiabilityPaymentsDue" xlink:to="us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl2" xlink:title="label: LesseeOperatingLeaseLiabilityPaymentsDue to us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongtermDebtCurrentAndNoncurrentAbstract" xlink:label="LongtermDebtCurrentAndNoncurrentAbstract" xlink:title="LongtermDebtCurrentAndNoncurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl">Long-Term Obligations [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongtermDebtCurrentAndNoncurrentAbstract" xlink:to="us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" xlink:title="label: LongtermDebtCurrentAndNoncurrentAbstract to us-gaap_LongtermDebtCurrentAndNoncurrentAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LandMember" xlink:label="LandMember" xlink:title="LandMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandMember_lbl" xml:lang="en-US" id="us-gaap_LandMember_lbl">Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember_lbl" xlink:title="label: LandMember to us-gaap_LandMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LandMember_lbl1" xml:lang="en-US" id="us-gaap_LandMember_lbl1">Undeveloped Land in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandMember" xlink:to="us-gaap_LandMember_lbl1" xlink:title="label: LandMember to us-gaap_LandMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LandImprovementsMember" xlink:label="LandImprovementsMember" xlink:title="LandImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandImprovementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LandImprovementsMember_lbl" xml:lang="en-US" id="us-gaap_LandImprovementsMember_lbl">Land Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandImprovementsMember" xlink:to="us-gaap_LandImprovementsMember_lbl" xlink:title="label: LandImprovementsMember to us-gaap_LandImprovementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LandImprovementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LandImprovementsMember_lbl1" xml:lang="en-US" id="us-gaap_LandImprovementsMember_lbl1">Land Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LandImprovementsMember" xlink:to="us-gaap_LandImprovementsMember_lbl1" xlink:title="label: LandImprovementsMember to us-gaap_LandImprovementsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LeaseholdImprovementsMember" xlink:label="LeaseholdImprovementsMember" xlink:title="LeaseholdImprovementsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LeaseholdImprovementsMember_lbl" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember_lbl">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember_lbl" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LeaseholdImprovementsMember_lbl1" xml:lang="en-US" id="us-gaap_LeaseholdImprovementsMember_lbl1">Leasehold Improvements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LeaseholdImprovementsMember" xlink:to="us-gaap_LeaseholdImprovementsMember_lbl1" xlink:title="label: LeaseholdImprovementsMember to us-gaap_LeaseholdImprovementsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LegalMattersAndContingenciesTextBlock" xlink:label="LegalMattersAndContingenciesTextBlock" xlink:title="LegalMattersAndContingenciesTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl">Legal Proceedings</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LegalMattersAndContingenciesTextBlock" xlink:to="us-gaap_LegalMattersAndContingenciesTextBlock_lbl" xlink:title="label: LegalMattersAndContingenciesTextBlock to us-gaap_LegalMattersAndContingenciesTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xml:lang="en-US" id="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1">Legal Matters and Contingencies [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LegalMattersAndContingenciesTextBlock" xlink:to="us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" xlink:title="label: LegalMattersAndContingenciesTextBlock to us-gaap_LegalMattersAndContingenciesTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquityAbstract" xlink:label="LiabilitiesAndStockholdersEquityAbstract" xlink:title="LiabilitiesAndStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl">LIABILITIES AND STOCKHOLDERS' EQUITY</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1">Liabilities and Equity [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquityAbstract" xlink:to="us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquityAbstract to us-gaap_LiabilitiesAndStockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesAndStockholdersEquity" xlink:label="LiabilitiesAndStockholdersEquity" xlink:title="LiabilitiesAndStockholdersEquity" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl">Total liabilities and stockholders' equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesAndStockholdersEquity_lbl1">Liabilities and Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesAndStockholdersEquity" xlink:to="us-gaap_LiabilitiesAndStockholdersEquity_lbl1" xlink:title="label: LiabilitiesAndStockholdersEquity to us-gaap_LiabilitiesAndStockholdersEquity_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Liabilities" xlink:label="Liabilities" xlink:title="Liabilities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_Liabilities_lbl" xml:lang="en-US" id="us-gaap_Liabilities_lbl">Total liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Liabilities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Liabilities_lbl1" xml:lang="en-US" id="us-gaap_Liabilities_lbl1">Liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Liabilities" xlink:to="us-gaap_Liabilities_lbl1" xlink:title="label: Liabilities to us-gaap_Liabilities_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrent" xlink:label="LiabilitiesCurrent" xlink:title="LiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl">Total current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrent_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrent_lbl1">Liabilities, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrent" xlink:to="us-gaap_LiabilitiesCurrent_lbl1" xlink:title="label: LiabilitiesCurrent to us-gaap_LiabilitiesCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LiabilitiesCurrentAbstract" xlink:label="LiabilitiesCurrentAbstract" xlink:title="LiabilitiesCurrentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl">Current liabilities:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LiabilitiesCurrentAbstract_lbl1" xml:lang="en-US" id="us-gaap_LiabilitiesCurrentAbstract_lbl1">Liabilities, Current [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilitiesCurrentAbstract" xlink:to="us-gaap_LiabilitiesCurrentAbstract_lbl1" xlink:title="label: LiabilitiesCurrentAbstract to us-gaap_LiabilitiesCurrentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LitigationSettlementAmountAwardedFromOtherParty" xlink:label="LitigationSettlementAmountAwardedFromOtherParty" xlink:title="LitigationSettlementAmountAwardedFromOtherParty" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl">Award from arbitration panel</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedFromOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" xlink:title="label: LitigationSettlementAmountAwardedFromOtherParty to us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1">Litigation Settlement, Amount Awarded from Other Party</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedFromOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" xlink:title="label: LitigationSettlementAmountAwardedFromOtherParty to us-gaap_LitigationSettlementAmountAwardedFromOtherParty_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LitigationSettlementAmountAwardedToOtherParty" xlink:label="LitigationSettlementAmountAwardedToOtherParty" xlink:title="LitigationSettlementAmountAwardedToOtherParty" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xml:lang="en-US" id="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1">Litigation Settlement, Amount Awarded to Other Party</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationSettlementAmountAwardedToOtherParty" xlink:to="us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" xlink:title="label: LitigationSettlementAmountAwardedToOtherParty to us-gaap_LitigationSettlementAmountAwardedToOtherParty_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LoansPayableToBank" xlink:label="LoansPayableToBank" xlink:title="LoansPayableToBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LoansPayableToBank_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LoansPayableToBank_lbl" xml:lang="en-US" id="us-gaap_LoansPayableToBank_lbl">Mortgage debt</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LoansPayableToBank_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LoansPayableToBank_lbl1" xml:lang="en-US" id="us-gaap_LoansPayableToBank_lbl1">Loans Payable to Bank</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LoansPayableToBank" xlink:to="us-gaap_LoansPayableToBank_lbl1" xlink:title="label: LoansPayableToBank to us-gaap_LoansPayableToBank_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebt" xlink:label="LongTermDebt" xlink:title="LongTermDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_LongTermDebt_lbl" xml:lang="en-US" id="us-gaap_LongTermDebt_lbl">Total debt and mortgage maturities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebt_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebt_lbl1">Long-Term Debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebt" xlink:to="us-gaap_LongTermDebt_lbl1" xlink:title="label: LongTermDebt to us-gaap_LongTermDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:label="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:title="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl">Convertible Debt [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1">Long-Term Debt, by Type, Current and Noncurrent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract" xlink:to="us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" xlink:title="label: LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract to us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtCurrent" xlink:label="LongTermDebtCurrent" xlink:title="LongTermDebtCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtCurrent_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_LongTermDebtCurrent_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtCurrent_lbl">Less: Current portion included in other current liabilities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtCurrent" xlink:to="us-gaap_LongTermDebtCurrent_lbl" xlink:title="label: LongTermDebtCurrent to us-gaap_LongTermDebtCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtCurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtCurrent_lbl1">Long-Term Debt, Current Maturities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtCurrent" xlink:to="us-gaap_LongTermDebtCurrent_lbl1" xlink:title="label: LongTermDebtCurrent to us-gaap_LongTermDebtCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtNoncurrent" xlink:label="LongTermDebtNoncurrent" xlink:title="LongTermDebtNoncurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtNoncurrent_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtNoncurrent_lbl">Total long-term debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtNoncurrent" xlink:to="us-gaap_LongTermDebtNoncurrent_lbl" xlink:title="label: LongTermDebtNoncurrent to us-gaap_LongTermDebtNoncurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtNoncurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtNoncurrent_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtNoncurrent_lbl1">Long-Term Debt, Excluding Current Maturities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtNoncurrent" xlink:to="us-gaap_LongTermDebtNoncurrent_lbl1" xlink:title="label: LongTermDebtNoncurrent to us-gaap_LongTermDebtNoncurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl">Thereafter</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1">Long-Term Debt, Maturity, after Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl">2023</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1">Long-Term Debt, Maturity, Year One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermLoansFromBank" xlink:label="LongTermLoansFromBank" xlink:title="LongTermLoansFromBank" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermLoansFromBank_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermLoansFromBank_lbl" xml:lang="en-US" id="us-gaap_LongTermLoansFromBank_lbl">Long-term mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermLoansFromBank" xlink:to="us-gaap_LongTermLoansFromBank_lbl" xlink:title="label: LongTermLoansFromBank to us-gaap_LongTermLoansFromBank_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl">2027</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1">Long-Term Debt, Maturity, Year Five</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl">2026</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1">Long-Term Debt, Maturity, Year Four</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl">2025</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1">Long-Term Debt, Maturity, Year Three</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:label="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:title="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl">2024</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xml:lang="en-US" id="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1">Long-Term Debt, Maturity, Year Two</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo" xlink:to="us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" xlink:title="label: LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo to us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_LossContingencyNumberOfPlaintiffs" xlink:label="LossContingencyNumberOfPlaintiffs" xlink:title="LossContingencyNumberOfPlaintiffs" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xml:lang="en-US" id="us-gaap_LossContingencyNumberOfPlaintiffs_lbl">Number of plaintiffs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyNumberOfPlaintiffs" xlink:to="us-gaap_LossContingencyNumberOfPlaintiffs_lbl" xlink:title="label: LossContingencyNumberOfPlaintiffs to us-gaap_LossContingencyNumberOfPlaintiffs_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyNumberOfPlaintiffs" xlink:to="us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" xlink:title="label: LossContingencyNumberOfPlaintiffs to us-gaap_LossContingencyNumberOfPlaintiffs_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingenciesLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingenciesLineItems_lbl" xml:lang="en-US" id="us-gaap_LossContingenciesLineItems_lbl">Loss Contingencies [Line Items]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingenciesTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingenciesTable_lbl" xml:lang="en-US" id="us-gaap_LossContingenciesTable_lbl">Loss Contingencies [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingenciesTable" xlink:to="us-gaap_LossContingenciesTable_lbl" xlink:title="label: LossContingenciesTable to us-gaap_LossContingenciesTable_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xml:lang="en-US" id="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl">Legal Procedings [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LossContingencyClaimsQuantitiesAbstract" xlink:to="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" xlink:title="label: LossContingencyClaimsQuantitiesAbstract to us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1" xml:lang="en-US" id="us-gaap_LossContingencyClaimsQuantitiesAbstract_lbl1">Loss Contingency, Quantities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ManufacturingFacilityMember" xlink:label="ManufacturingFacilityMember" xlink:title="ManufacturingFacilityMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ManufacturingFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ManufacturingFacilityMember_lbl" xml:lang="en-US" id="us-gaap_ManufacturingFacilityMember_lbl">Manufacturing Facility [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_MaturitiesOfLongTermDebtAbstract" xlink:label="MaturitiesOfLongTermDebtAbstract" xlink:title="MaturitiesOfLongTermDebtAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MaturitiesOfLongTermDebtAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MaturitiesOfLongTermDebtAbstract_lbl" xml:lang="en-US" id="us-gaap_MaturitiesOfLongTermDebtAbstract_lbl">Debt Maturities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_MinorityInterestLineItems" xlink:label="MinorityInterestLineItems" xlink:title="MinorityInterestLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestLineItems_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestLineItems_lbl">Noncontrolling Interest [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_MinorityInterestDecreaseFromRedemptions" xlink:label="MinorityInterestDecreaseFromRedemptions" xlink:title="MinorityInterestDecreaseFromRedemptions" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestDecreaseFromRedemptions_lbl1">Noncontrolling Interest, Decrease from Redemptions or Purchase of Interests</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_MinorityInterestTable" xlink:label="MinorityInterestTable" xlink:title="MinorityInterestTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestTable_lbl" xml:lang="en-US" id="us-gaap_MinorityInterestTable_lbl">Noncontrolling Interest [Table]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1" xml:lang="en-US" id="us-gaap_MinorityInterestPeriodIncreaseDecrease_lbl1">Noncontrolling Interest, Period Increase (Decrease)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_NetCashProvidedByUsedInFinancingActivities_lbl1">Net Cash Provided by (Used in) Financing Activities</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:label="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:title="NewAccountingPronouncementsPolicyPolicyTextBlock" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NewAccountingPronouncementsPolicyPolicyTextBlock" xlink:to="us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" xlink:title="label: NewAccountingPronouncementsPolicyPolicyTextBlock to us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_NonoperatingIncomeExpenseAbstract" xlink:label="NonoperatingIncomeExpenseAbstract" xlink:title="NonoperatingIncomeExpenseAbstract" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_NotesPayableFairValueDisclosure_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_NotesPayableFairValueDisclosure_lbl" xml:lang="en-US" id="us-gaap_NotesPayableFairValueDisclosure_lbl">Fair value of convertible notes</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiability_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiability_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiability_lbl1">Lease liabilities</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeasePayments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeasePayments_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeasePayments_lbl1">Operating Lease, Payments</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseExpense" xlink:label="OperatingLeaseExpense" xlink:title="OperatingLeaseExpense" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseExpense_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseExpense_lbl">Rent expense</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:label="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" xlink:title="OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl">Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1" xml:lang="en-US" id="us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList_lbl1">Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingIncomeLoss" xlink:label="OperatingIncomeLoss" xlink:title="OperatingIncomeLoss" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLossCarryforwardsLineItems" xlink:label="OperatingLossCarryforwardsLineItems" xlink:title="OperatingLossCarryforwardsLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLossCarryforwardsLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLossCarryforwardsLineItems_lbl" xml:lang="en-US" id="us-gaap_OperatingLossCarryforwardsLineItems_lbl">Operating Loss Carryforwards [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OperatingLossCarryforwardsLineItems" xlink:to="us-gaap_OperatingLossCarryforwardsLineItems_lbl" xlink:title="label: OperatingLossCarryforwardsLineItems to us-gaap_OperatingLossCarryforwardsLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLossCarryforwards" xlink:label="OperatingLossCarryforwards" xlink:title="OperatingLossCarryforwards" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLossCarryforwards_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OperatingLossCarryforwards_lbl" xml:lang="en-US" id="us-gaap_OperatingLossCarryforwards_lbl">Net operating loss carryforwards</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OperatingLossCarryforwards_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OperatingLossCarryforwards_lbl1" xml:lang="en-US" id="us-gaap_OperatingLossCarryforwards_lbl1">Operating Loss Carryforwards</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OperatingLossCarryforwardsTable" xlink:label="OperatingLossCarryforwardsTable" xlink:title="OperatingLossCarryforwardsTable" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock" xlink:label="OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock" xlink:title="OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:label="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" xlink:title="OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherComprehensiveIncomeLossNetOfTax" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTax_lbl1" xlink:title="label: OtherComprehensiveIncomeLossNetOfTax to us-gaap_OtherComprehensiveIncomeLossNetOfTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsNoncurrent" xlink:label="OtherAssetsNoncurrent" xlink:title="OtherAssetsNoncurrent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherAssetsCurrent" xlink:label="OtherAssetsCurrent" xlink:title="OtherAssetsCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherAssetsCurrent_lbl" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl">Other current assets</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherAssetsCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherAssetsCurrent_lbl1" xml:lang="en-US" id="us-gaap_OtherAssetsCurrent_lbl1">Other Assets, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OtherAssetsCurrent" xlink:to="us-gaap_OtherAssetsCurrent_lbl1" xlink:title="label: OtherAssetsCurrent to us-gaap_OtherAssetsCurrent_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeLossTax" xlink:label="OtherComprehensiveIncomeLossTax" xlink:title="OtherComprehensiveIncomeLossTax" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherComprehensiveIncomeLossTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherComprehensiveIncomeLossTax_lbl1" xml:lang="en-US" id="us-gaap_OtherComprehensiveIncomeLossTax_lbl1">Other Comprehensive Income (Loss), Tax</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:label="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" xlink:title="OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherDebtSecuritiesMember" xlink:label="OtherDebtSecuritiesMember" xlink:title="OtherDebtSecuritiesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherDebtSecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherDebtSecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_OtherDebtSecuritiesMember_lbl">Other Municipal Debt Securities [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherLiabilitiesCurrent" xlink:label="OtherLiabilitiesCurrent" xlink:title="OtherLiabilitiesCurrent" />
    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_OtherLiabilitiesCurrent_lbl" xml:lang="en-US" id="us-gaap_OtherLiabilitiesCurrent_lbl">Other current liabilities</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherLiabilities" xlink:label="OtherLiabilities" xlink:title="OtherLiabilities" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_OtherLiabilitiesNoncurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_OtherLiabilitiesNoncurrent_lbl" xml:lang="en-US" id="us-gaap_OtherLiabilitiesNoncurrent_lbl">Long-term obligations</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_OtherNonoperatingIncomeExpense" xlink:label="OtherNonoperatingIncomeExpense" xlink:title="OtherNonoperatingIncomeExpense" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsForHedgeFinancingActivities" xlink:label="PaymentsForHedgeFinancingActivities" xlink:title="PaymentsForHedgeFinancingActivities" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl">Purchase of note hedges</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForHedgeFinancingActivities" xlink:to="us-gaap_PaymentsForHedgeFinancingActivities_lbl" xlink:title="label: PaymentsForHedgeFinancingActivities to us-gaap_PaymentsForHedgeFinancingActivities_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl1">Purchase of note hedges</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForHedgeFinancingActivities" xlink:to="us-gaap_PaymentsForHedgeFinancingActivities_lbl1" xlink:title="label: PaymentsForHedgeFinancingActivities to us-gaap_PaymentsForHedgeFinancingActivities_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForHedgeFinancingActivities_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForHedgeFinancingActivities_lbl2" xml:lang="en-US" id="us-gaap_PaymentsForHedgeFinancingActivities_lbl2">Payments for Hedge, Financing Activities</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForHedgeFinancingActivities" xlink:to="us-gaap_PaymentsForHedgeFinancingActivities_lbl2" xlink:title="label: PaymentsForHedgeFinancingActivities to us-gaap_PaymentsForHedgeFinancingActivities_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:label="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:title="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" xlink:title="label: PaymentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xml:lang="en-US" id="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1">Payment, Tax Withholding, Share-Based Payment Arrangement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsRelatedToTaxWithholdingForShareBasedCompensation" xlink:to="us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" xlink:title="label: PaymentsRelatedToTaxWithholdingForShareBasedCompensation to us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock" xlink:label="PaymentsForRepurchaseOfCommonStock" xlink:title="PaymentsForRepurchaseOfCommonStock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl">Repurchases and retirements of common stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForRepurchaseOfCommonStock" xlink:to="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" xlink:title="label: PaymentsForRepurchaseOfCommonStock to us-gaap_PaymentsForRepurchaseOfCommonStock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1">Shares repurchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForRepurchaseOfCommonStock" xlink:to="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" xlink:title="label: PaymentsForRepurchaseOfCommonStock to us-gaap_PaymentsForRepurchaseOfCommonStock_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" xml:lang="en-US" id="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2">Payments for Repurchase of Common Stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsForRepurchaseOfCommonStock" xlink:to="us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" xlink:title="label: PaymentsForRepurchaseOfCommonStock to us-gaap_PaymentsForRepurchaseOfCommonStock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsOfDebtIssuanceCosts" xlink:label="PaymentsOfDebtIssuanceCosts" xlink:title="PaymentsOfDebtIssuanceCosts" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl">0 percent convertible senior notes issuance costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsOfDebtIssuanceCosts" xlink:to="us-gaap_PaymentsOfDebtIssuanceCosts_lbl" xlink:title="label: PaymentsOfDebtIssuanceCosts to us-gaap_PaymentsOfDebtIssuanceCosts_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xml:lang="en-US" id="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1">Payments of Debt Issuance Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsOfDebtIssuanceCosts" xlink:to="us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" xlink:title="label: PaymentsOfDebtIssuanceCosts to us-gaap_PaymentsOfDebtIssuanceCosts_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireIntangibleAssets" xlink:label="PaymentsToAcquireIntangibleAssets" xlink:title="PaymentsToAcquireIntangibleAssets" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl">Acquisition of licenses and other assets, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1">Payments to Acquire Intangible Assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireIntangibleAssets" xlink:to="us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" xlink:title="label: PaymentsToAcquireIntangibleAssets to us-gaap_PaymentsToAcquireIntangibleAssets_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireBuildings" xlink:label="PaymentsToAcquireBuildings" xlink:title="PaymentsToAcquireBuildings" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireBuildings_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireBuildings_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireBuildings_lbl">Payment to acquire building</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireBuildings" xlink:to="us-gaap_PaymentsToAcquireBuildings_lbl" xlink:title="label: PaymentsToAcquireBuildings to us-gaap_PaymentsToAcquireBuildings_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:label="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:title="PaymentsToAcquireAvailableForSaleSecuritiesDebt" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl">Purchases of short-term investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1">Payments to Acquire Debt Securities, Available-for-Sale</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireAvailableForSaleSecuritiesDebt" xlink:to="us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" xlink:title="label: PaymentsToAcquireAvailableForSaleSecuritiesDebt to us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquireOtherInvestments" xlink:label="PaymentsToAcquireOtherInvestments" xlink:title="PaymentsToAcquireOtherInvestments" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireOtherInvestments_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquireOtherInvestments_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquireOtherInvestments_lbl">Purchases of strategic investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherInvestments" xlink:to="us-gaap_PaymentsToAcquireOtherInvestments_lbl" xlink:title="label: PaymentsToAcquireOtherInvestments to us-gaap_PaymentsToAcquireOtherInvestments_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquireOtherInvestments_lbl1">Payments to Acquire Other Investments</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquireOtherInvestments" xlink:to="us-gaap_PaymentsToAcquireOtherInvestments_lbl1" xlink:title="label: PaymentsToAcquireOtherInvestments to us-gaap_PaymentsToAcquireOtherInvestments_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipment" xlink:label="PaymentsToAcquirePropertyPlantAndEquipment" xlink:title="PaymentsToAcquirePropertyPlantAndEquipment" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl">Purchases of property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1">Payments to Acquire Property, Plant, and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipment" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipment to us-gaap_PaymentsToAcquirePropertyPlantAndEquipment_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:label="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:title="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl">Operating Facilities [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipmentAbstract to us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl1">Payments to Acquire Property, Plant, and Equipment [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToAcquirePropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl1" xlink:title="label: PaymentsToAcquirePropertyPlantAndEquipmentAbstract to us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PaymentsToMinorityShareholders" xlink:label="PaymentsToMinorityShareholders" xlink:title="PaymentsToMinorityShareholders" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToMinorityShareholders_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_PaymentsToMinorityShareholders_lbl" xml:lang="en-US" id="us-gaap_PaymentsToMinorityShareholders_lbl">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToMinorityShareholders" xlink:to="us-gaap_PaymentsToMinorityShareholders_lbl" xlink:title="label: PaymentsToMinorityShareholders to us-gaap_PaymentsToMinorityShareholders_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PaymentsToMinorityShareholders_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PaymentsToMinorityShareholders_lbl1" xml:lang="en-US" id="us-gaap_PaymentsToMinorityShareholders_lbl1">Payments to Noncontrolling Interests</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsToMinorityShareholders" xlink:to="us-gaap_PaymentsToMinorityShareholders_lbl1" xlink:title="label: PaymentsToMinorityShareholders to us-gaap_PaymentsToMinorityShareholders_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:label="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:title="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl">Employment Benefits</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:to="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" xlink:title="label: PensionAndOtherPostretirementBenefitsDisclosureTextBlock to us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" xml:lang="en-US" id="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1">Retirement Benefits [Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PensionAndOtherPostretirementBenefitsDisclosureTextBlock" xlink:to="us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" xlink:title="label: PensionAndOtherPostretirementBenefitsDisclosureTextBlock to us-gaap_PensionAndOtherPostretirementBenefitsDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PerformanceSharesMember" xlink:label="PerformanceSharesMember" xlink:title="PerformanceSharesMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PerformanceSharesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PerformanceSharesMember_lbl" xml:lang="en-US" id="us-gaap_PerformanceSharesMember_lbl">PRSUs [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PerformanceSharesMember" xlink:to="us-gaap_PerformanceSharesMember_lbl" xlink:title="label: PerformanceSharesMember to us-gaap_PerformanceSharesMember_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOfWarrants" xlink:label="ProceedsFromIssuanceOfWarrants" xlink:title="ProceedsFromIssuanceOfWarrants" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromIssuanceOfWarrants_lbl1">Proceeds from Issuance of Warrants</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:label="ProceedsFromIssuanceOrSaleOfEquityAbstract" xlink:title="ProceedsFromIssuanceOrSaleOfEquityAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromStockOptionsExercised" xlink:to="us-gaap_ProceedsFromStockOptionsExercised_lbl" xlink:title="label: ProceedsFromStockOptionsExercised to us-gaap_ProceedsFromStockOptionsExercised_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProceedsFromStockOptionsExercised_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProceedsFromStockOptionsExercised_lbl1" xml:lang="en-US" id="us-gaap_ProceedsFromStockOptionsExercised_lbl1">Proceeds from Stock Options Exercised</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProductMember" xlink:label="ProductMember" xlink:title="ProductMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProductMember_lbl" xml:lang="en-US" id="us-gaap_ProductMember_lbl">TEGSEDI and WAYLIVRA Revenue, Net [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProductMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProductMember_lbl1" xml:lang="en-US" id="us-gaap_ProductMember_lbl1">Product [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductMember" xlink:to="us-gaap_ProductMember_lbl1" xlink:title="label: ProductMember to us-gaap_ProductMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ProfitLoss" xlink:label="ProfitLoss" xlink:title="ProfitLoss" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_ProfitLoss_lbl" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ProfitLoss_lbl1" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl1">Net income (loss)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl1" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_ProfitLoss_lbl2" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl2">Net loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl2" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl2" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ProfitLoss_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ProfitLoss_lbl3" xml:lang="en-US" id="us-gaap_ProfitLoss_lbl3">Net Income (Loss), Including Portion Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProfitLoss" xlink:to="us-gaap_ProfitLoss_lbl3" xlink:title="label: ProfitLoss to us-gaap_ProfitLoss_lbl3" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl">Estimated useful life</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentUsefulLife" xlink:to="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl" xlink:title="label: PropertyPlantAndEquipmentUsefulLife to us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl1">Property, Plant and Equipment, Useful Life</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentUsefulLife" xlink:to="us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl1" xlink:title="label: PropertyPlantAndEquipmentUsefulLife to us-gaap_PropertyPlantAndEquipmentUsefulLife_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentLineItems" xlink:label="PropertyPlantAndEquipmentLineItems" xlink:title="PropertyPlantAndEquipmentLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentLineItems_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentLineItems_lbl">Property, Plant and Equipment [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentLineItems" xlink:to="us-gaap_PropertyPlantAndEquipmentLineItems_lbl" xlink:title="label: PropertyPlantAndEquipmentLineItems to us-gaap_PropertyPlantAndEquipmentLineItems_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentTextBlock" xlink:label="PropertyPlantAndEquipmentTextBlock" xlink:title="PropertyPlantAndEquipmentTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl">Property, Plant and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentTextBlock" xlink:to="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl" xlink:title="label: PropertyPlantAndEquipmentTextBlock to us-gaap_PropertyPlantAndEquipmentTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl1">Property, Plant and Equipment [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentTextBlock" xlink:to="us-gaap_PropertyPlantAndEquipmentTextBlock_lbl1" xlink:title="label: PropertyPlantAndEquipmentTextBlock to us-gaap_PropertyPlantAndEquipmentTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis" xlink:label="PropertyPlantAndEquipmentByTypeAxis" xlink:title="PropertyPlantAndEquipmentByTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl">Long-Lived Tangible Asset [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentByTypeAxis" xlink:to="us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" xlink:title="label: PropertyPlantAndEquipmentByTypeAxis to us-gaap_PropertyPlantAndEquipmentByTypeAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentAbstract" xlink:label="PropertyPlantAndEquipmentAbstract" xlink:title="PropertyPlantAndEquipmentAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentAbstract_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentAbstract_lbl">Property, Plant and Equipment [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentAbstract_lbl" xlink:title="label: PropertyPlantAndEquipmentAbstract to us-gaap_PropertyPlantAndEquipmentAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentAbstract_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentAbstract_lbl1">Property, Plant and Equipment [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentAbstract" xlink:to="us-gaap_PropertyPlantAndEquipmentAbstract_lbl1" xlink:title="label: PropertyPlantAndEquipmentAbstract to us-gaap_PropertyPlantAndEquipmentAbstract_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl">Property, plant and equipment, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl1">Property, plant and equipment, net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl1" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentNet_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentNet_lbl2" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentNet_lbl2">Property, Plant and Equipment, Net</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentNet" xlink:to="us-gaap_PropertyPlantAndEquipmentNet_lbl2" xlink:title="label: PropertyPlantAndEquipmentNet to us-gaap_PropertyPlantAndEquipmentNet_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_PropertyPlantAndEquipmentGross" xlink:label="PropertyPlantAndEquipmentGross" xlink:title="PropertyPlantAndEquipmentGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentGross_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentGross_lbl">Property, plant and equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentGross" xlink:to="us-gaap_PropertyPlantAndEquipmentGross_lbl" xlink:title="label: PropertyPlantAndEquipmentGross to us-gaap_PropertyPlantAndEquipmentGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentGross_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentGross_lbl1">Property, Plant and Equipment, Gross</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentGross" xlink:to="us-gaap_PropertyPlantAndEquipmentGross_lbl1" xlink:title="label: PropertyPlantAndEquipmentGross to us-gaap_PropertyPlantAndEquipmentGross_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl">Property, Plant and Equipment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentPolicyTextBlock" xlink:to="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl" xlink:title="label: PropertyPlantAndEquipmentPolicyTextBlock to us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_PropertyPlantAndEquipmentPolicyTextBlock_lbl1">Property, Plant and Equipment, Policy [Policy Text Block]</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="QuarterlyFinancialInformationTextBlock" xlink:to="us-gaap_QuarterlyFinancialInformationTextBlock_lbl" xlink:title="label: QuarterlyFinancialInformationTextBlock to us-gaap_QuarterlyFinancialInformationTextBlock_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockUnitsRSUMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestrictedStockUnitsRSUMember_lbl" xml:lang="en-US" id="us-gaap_RestrictedStockUnitsRSUMember_lbl">Restricted Stock Units [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockUnitsRSUMember" xlink:to="us-gaap_RestrictedStockUnitsRSUMember_lbl" xlink:title="label: RestrictedStockUnitsRSUMember to us-gaap_RestrictedStockUnitsRSUMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xml:lang="en-US" id="us-gaap_RestrictedStockUnitsRSUMember_lbl1">RSUs [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockUnitsRSUMember" xlink:to="us-gaap_RestrictedStockUnitsRSUMember_lbl1" xlink:title="label: RestrictedStockUnitsRSUMember to us-gaap_RestrictedStockUnitsRSUMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockUnitsRSUMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestrictedStockUnitsRSUMember_lbl2" xml:lang="en-US" id="us-gaap_RestrictedStockUnitsRSUMember_lbl2">Restricted Stock Units (RSUs) [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockUnitsRSUMember" xlink:to="us-gaap_RestrictedStockUnitsRSUMember_lbl2" xlink:title="label: RestrictedStockUnitsRSUMember to us-gaap_RestrictedStockUnitsRSUMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RestrictedStockMember" xlink:label="RestrictedStockMember" xlink:title="RestrictedStockMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RestrictedStockMember_lbl" xml:lang="en-US" id="us-gaap_RestrictedStockMember_lbl">Restricted Stock Awards [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockMember" xlink:to="us-gaap_RestrictedStockMember_lbl" xlink:title="label: RestrictedStockMember to us-gaap_RestrictedStockMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RestrictedStockMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RestrictedStockMember_lbl1" xml:lang="en-US" id="us-gaap_RestrictedStockMember_lbl1">Restricted Stock [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RestrictedStockMember" xlink:to="us-gaap_RestrictedStockMember_lbl1" xlink:title="label: RestrictedStockMember to us-gaap_RestrictedStockMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RetainedEarningsAccumulatedDeficit" xlink:label="RetainedEarningsAccumulatedDeficit" xlink:title="RetainedEarningsAccumulatedDeficit" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl">Accumulated deficit</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1">Retained Earnings (Accumulated Deficit)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsAccumulatedDeficit" xlink:to="us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" xlink:title="label: RetainedEarningsAccumulatedDeficit to us-gaap_RetainedEarningsAccumulatedDeficit_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RetainedEarningsMember" xlink:label="RetainedEarningsMember" xlink:title="RetainedEarningsMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RetainedEarningsMember_lbl" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl">Accumulated Deficit [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RetainedEarningsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RetainedEarningsMember_lbl1" xml:lang="en-US" id="us-gaap_RetainedEarningsMember_lbl1">Retained Earnings [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RetainedEarningsMember" xlink:to="us-gaap_RetainedEarningsMember_lbl1" xlink:title="label: RetainedEarningsMember to us-gaap_RetainedEarningsMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="RevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl">Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1">Revenue from Contract with Customer, Excluding Assessed Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: RevenueFromContractWithCustomerExcludingAssessedTax to us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerPolicyTextBlock" xlink:label="RevenueFromContractWithCustomerPolicyTextBlock" xlink:title="RevenueFromContractWithCustomerPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl">Revenue Recognition</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerPolicyTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" xlink:title="label: RevenueFromContractWithCustomerPolicyTextBlock to us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1">Revenue from Contract with Customer [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerPolicyTextBlock" xlink:to="us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" xlink:title="label: RevenueFromContractWithCustomerPolicyTextBlock to us-gaap_RevenueFromContractWithCustomerPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerMember" xlink:label="RevenueFromContractWithCustomerMember" xlink:title="RevenueFromContractWithCustomerMember" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl">Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerMember_lbl1">Revenue from Contract with Customer Benchmark [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerMember" xlink:to="us-gaap_RevenueFromContractWithCustomerMember_lbl1" xlink:title="label: RevenueFromContractWithCustomerMember to us-gaap_RevenueFromContractWithCustomerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueFromContractWithCustomerAbstract" xlink:label="RevenueFromContractWithCustomerAbstract" xlink:title="RevenueFromContractWithCustomerAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl">Revenue Recognition [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1">Revenue from Contract with Customer [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerAbstract" xlink:to="us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" xlink:title="label: RevenueFromContractWithCustomerAbstract to us-gaap_RevenueFromContractWithCustomerAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenueRecognitionPolicyTextBlock" xlink:label="RevenueRecognitionPolicyTextBlock" xlink:title="RevenueRecognitionPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_RevenueRecognitionPolicyTextBlock_lbl">Deferred Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognitionPolicyTextBlock" xlink:to="us-gaap_RevenueRecognitionPolicyTextBlock_lbl" xlink:title="label: RevenueRecognitionPolicyTextBlock to us-gaap_RevenueRecognitionPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1">Revenue [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueRecognitionPolicyTextBlock" xlink:to="us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" xlink:title="label: RevenueRecognitionPolicyTextBlock to us-gaap_RevenueRecognitionPolicyTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_RevenuesAbstract" xlink:label="RevenuesAbstract" xlink:title="RevenuesAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenuesAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_RevenuesAbstract_lbl" xml:lang="en-US" id="us-gaap_RevenuesAbstract_lbl">Revenue:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenuesAbstract" xlink:to="us-gaap_RevenuesAbstract_lbl" xlink:title="label: RevenuesAbstract to us-gaap_RevenuesAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_RevenuesAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_RevenuesAbstract_lbl1" xml:lang="en-US" id="us-gaap_RevenuesAbstract_lbl1">Revenues [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenuesAbstract" xlink:to="us-gaap_RevenuesAbstract_lbl1" xlink:title="label: RevenuesAbstract to us-gaap_RevenuesAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_Revenues" xlink:label="Revenues" xlink:title="Revenues" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Revenues_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_Revenues_lbl" xml:lang="en-US" id="us-gaap_Revenues_lbl">Revenue</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Revenues" xlink:to="us-gaap_Revenues_lbl" xlink:title="label: Revenues to us-gaap_Revenues_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_Revenues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_Revenues_lbl1" xml:lang="en-US" id="us-gaap_Revenues_lbl1">Revenues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Revenues" xlink:to="us-gaap_Revenues_lbl1" xlink:title="label: Revenues to us-gaap_Revenues_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl">Award term</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Expiration Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl">Vesting percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xml:lang="en-US" id="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Award Vesting Rights, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" xlink:title="label: SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage to us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:label="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" xlink:title="SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SaleAndLeasebackTransactionGainLossNet" xlink:label="SaleAndLeasebackTransactionGainLossNet" xlink:title="SaleAndLeasebackTransactionGainLossNet" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:label="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" xlink:title="ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock" xlink:label="ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock" xlink:title="ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Outstanding, Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_lbl3" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodStartLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1">Outstanding at beginning of period (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Outstanding, Weighted Average Exercise Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Grants in Period, Weighted Average Grant Date Fair Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl">Cancelled/forfeited/expired (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Forfeitures and Expirations in Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod to us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl">Number of Shares [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Outstanding [Roll Forward]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl" xml:lang="en-US" id="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_lbl">Equity Award [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:label="ShareBasedCompensationOptionAndIncentivePlansPolicy" xlink:title="ShareBasedCompensationOptionAndIncentivePlansPolicy" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SharesIssued" xlink:label="SharesIssued" xlink:title="SharesIssued" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfFinancialPositionAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfFinancialPositionAbstract_lbl">CONSOLIDATED BALANCE SHEETS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfFinancialPositionAbstract" xlink:to="us-gaap_StatementOfFinancialPositionAbstract_lbl" xlink:title="label: StatementOfFinancialPositionAbstract to us-gaap_StatementOfFinancialPositionAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:label="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:title="StatementOfIncomeAndComprehensiveIncomeAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl">CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfIncomeAndComprehensiveIncomeAbstract" xlink:to="us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" xlink:title="label: StatementOfIncomeAndComprehensiveIncomeAbstract to us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementBusinessSegmentsAxis" xlink:label="StatementBusinessSegmentsAxis" xlink:title="StatementBusinessSegmentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementBusinessSegmentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementBusinessSegmentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementBusinessSegmentsAxis_lbl">Segments [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementClassOfStockAxis" xlink:label="StatementClassOfStockAxis" xlink:title="StatementClassOfStockAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementClassOfStockAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementClassOfStockAxis_lbl" xml:lang="en-US" id="us-gaap_StatementClassOfStockAxis_lbl">Class of Stock [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="StatementEquityComponentsAxis" xlink:title="StatementEquityComponentsAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementEquityComponentsAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementEquityComponentsAxis_lbl" xml:lang="en-US" id="us-gaap_StatementEquityComponentsAxis_lbl">Equity Components [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementEquityComponentsAxis" xlink:to="us-gaap_StatementEquityComponentsAxis_lbl" xlink:title="label: StatementEquityComponentsAxis to us-gaap_StatementEquityComponentsAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementLineItems" xlink:label="StatementLineItems" xlink:title="StatementLineItems" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementLineItems_lbl" xml:lang="en-US" id="us-gaap_StatementLineItems_lbl">Statement [Line Items]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfCashFlowsAbstract" xlink:label="StatementOfCashFlowsAbstract" xlink:title="StatementOfCashFlowsAbstract" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfCashFlowsAbstract" xlink:to="us-gaap_StatementOfCashFlowsAbstract_lbl" xlink:title="label: StatementOfCashFlowsAbstract to us-gaap_StatementOfCashFlowsAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementTable" xlink:label="StatementTable" xlink:title="StatementTable" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementTable_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementTable_lbl" xml:lang="en-US" id="us-gaap_StatementTable_lbl">Statement [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementTable" xlink:to="us-gaap_StatementTable_lbl" xlink:title="label: StatementTable to us-gaap_StatementTable_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StatementOfStockholdersEquityAbstract" xlink:label="StatementOfStockholdersEquityAbstract" xlink:title="StatementOfStockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StatementOfStockholdersEquityAbstract_lbl">CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StatementOfStockholdersEquityAbstract" xlink:to="us-gaap_StatementOfStockholdersEquityAbstract_lbl" xlink:title="label: StatementOfStockholdersEquityAbstract to us-gaap_StatementOfStockholdersEquityAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockRepurchaseProgramAuthorizedAmount1" xlink:label="StockRepurchaseProgramAuthorizedAmount1" xlink:title="StockRepurchaseProgramAuthorizedAmount1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl">Authorized amount of share repurchase program</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1">Stock Repurchase Program, Authorized Amount</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchaseProgramAuthorizedAmount1" xlink:to="us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" xlink:title="label: StockRepurchaseProgramAuthorizedAmount1 to us-gaap_StockRepurchaseProgramAuthorizedAmount1_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodValueShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl">Issuance of common stock in connection with employee stock plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1">Shares Issued, Value, Share-Based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodValueShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodValueShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:label="StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:title="StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl">Shares purchased and issued under ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl" xlink:title="label: StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans to us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1">Stock Issued During Period, Shares, Employee Stock Purchase Plans</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans" xlink:to="us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans to us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:label="StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:title="StockIssuedDuringPeriodSharesShareBasedCompensationGross" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl">Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1">Shares Issued, Shares, Share-Based Payment Arrangement, before Forfeiture</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensationGross" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensationGross to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl">Shares issued (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" xlink:title="label: StockIssuedDuringPeriodSharesNewIssues to us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1">Stock Issued During Period, Shares, New Issues</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesNewIssues" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesNewIssues to us-gaap_StockIssuedDuringPeriodSharesNewIssues_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl">Issuance of common stock in connection with employee stock plans (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesShareBasedCompensation" xlink:to="us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesShareBasedCompensation to us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl">Shares repurchased (in shares)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedDuringPeriodShares_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedDuringPeriodShares_lbl1">Stock Repurchased During Period, Shares</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodValue" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodValue to us-gaap_StockRepurchasedAndRetiredDuringPeriodValue_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xml:lang="en-US" id="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1">Share-Based Compensation Arrangement by Share-Based Payment Award, Options, Exercises in Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockIssuedDuringPeriodSharesStockOptionsExercised" xlink:to="us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" xlink:title="label: StockIssuedDuringPeriodSharesStockOptionsExercised to us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" xlink:role="http://www.xbrl.org/2009/role/negatedLabel" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl">Repurchases and retirements of common stock (in shares)</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xml:lang="en-US" id="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1">Stock Repurchased and Retired During Period, Shares</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockRepurchasedAndRetiredDuringPeriodShares" xlink:to="us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" xlink:title="label: StockRepurchasedAndRetiredDuringPeriodShares to us-gaap_StockRepurchasedAndRetiredDuringPeriodShares_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquity_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquity_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquity_lbl1">Stockholders' Equity Attributable to Parent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquity" xlink:to="us-gaap_StockholdersEquity_lbl1" xlink:title="label: StockholdersEquity to us-gaap_StockholdersEquity_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl">Stockholders' Equity</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityNoteDisclosureTextBlock" xlink:to="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" xlink:title="label: StockholdersEquityNoteDisclosureTextBlock to us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityNoteDisclosureTextBlock" xlink:to="us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl1" xlink:title="label: StockholdersEquityNoteDisclosureTextBlock to us-gaap_StockholdersEquityNoteDisclosureTextBlock_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:label="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:title="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:role="http://www.xbrl.org/2003/role/periodEndLabel" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1">Balance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xml:lang="en-US" id="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2">Stockholders' Equity, Including Portion Attributable to Noncontrolling Interest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest" xlink:to="us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" xlink:title="label: StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest to us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityAbstract" xlink:label="StockholdersEquityAbstract" xlink:title="StockholdersEquityAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityAbstract_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl">Stockholders' equity:</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityAbstract_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityAbstract_lbl1">Stockholders' Equity Attributable to Parent [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityAbstract" xlink:to="us-gaap_StockholdersEquityAbstract_lbl1" xlink:title="label: StockholdersEquityAbstract to us-gaap_StockholdersEquityAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityNoteAbstract" xlink:label="StockholdersEquityNoteAbstract" xlink:title="StockholdersEquityNoteAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityNoteAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityNoteAbstract_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityNoteAbstract_lbl">Stockholders' Equity [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_StockholdersEquityPolicyTextBlock" xlink:label="StockholdersEquityPolicyTextBlock" xlink:title="StockholdersEquityPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_StockholdersEquityPolicyTextBlock_lbl" xml:lang="en-US" id="us-gaap_StockholdersEquityPolicyTextBlock_lbl">Accumulated Other Comprehensive Loss</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityPolicyTextBlock" xlink:to="us-gaap_StockholdersEquityPolicyTextBlock_lbl" xlink:title="label: StockholdersEquityPolicyTextBlock to us-gaap_StockholdersEquityPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_StockholdersEquityPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_StockholdersEquityPolicyTextBlock_lbl1" xml:lang="en-US" id="us-gaap_StockholdersEquityPolicyTextBlock_lbl1">Stockholders' Equity, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockholdersEquityPolicyTextBlock" xlink:to="us-gaap_StockholdersEquityPolicyTextBlock_lbl1" xlink:title="label: StockholdersEquityPolicyTextBlock to us-gaap_StockholdersEquityPolicyTextBlock_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeDomain_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventTypeDomain_lbl">Subsequent Event Type [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventTypeDomain_lbl" xlink:title="label: SubsequentEventTypeDomain to us-gaap_SubsequentEventTypeDomain_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventMember_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventMember_lbl">Subsequent Event [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventMember" xlink:to="us-gaap_SubsequentEventMember_lbl" xlink:title="label: SubsequentEventMember to us-gaap_SubsequentEventMember_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="SubsequentEventTypeAxis" xlink:title="SubsequentEventTypeAxis" />
    <link:label xlink:type="resource" xlink:label="us-gaap_SubsequentEventTypeAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_SubsequentEventTypeAxis_lbl" xml:lang="en-US" id="us-gaap_SubsequentEventTypeAxis_lbl">Subsequent Event Type [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeAxis_lbl" xlink:title="label: SubsequentEventTypeAxis to us-gaap_SubsequentEventTypeAxis_lbl" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_TaxCreditCarryforwardLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_TaxCreditCarryforwardLineItems_lbl" xml:lang="en-US" id="us-gaap_TaxCreditCarryforwardLineItems_lbl">Tax Credit Carryforwards [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_USTreasurySecuritiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_USTreasurySecuritiesMember_lbl" xml:lang="en-US" id="us-gaap_USTreasurySecuritiesMember_lbl">Debt Securities Issued by the U.S. Treasury [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_USTreasurySecuritiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_USTreasurySecuritiesMember_lbl1" xml:lang="en-US" id="us-gaap_USTreasurySecuritiesMember_lbl1">US Treasury Securities [Member]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_VestingAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_VestingAxis_lbl" xml:lang="en-US" id="us-gaap_VestingAxis_lbl">Vesting [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_VestingDomain" xlink:label="VestingDomain" xlink:title="VestingDomain" />
    <link:label xlink:type="resource" xlink:label="us-gaap_VestingDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_VestingDomain_lbl" xml:lang="en-US" id="us-gaap_VestingDomain_lbl">Vesting [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="VestingDomain" xlink:to="us-gaap_VestingDomain_lbl" xlink:title="label: VestingDomain to us-gaap_VestingDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease" xlink:label="ValuationAllowancesAndReservesPeriodIncreaseDecrease" xlink:title="ValuationAllowancesAndReservesPeriodIncreaseDecrease" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl" xml:lang="en-US" id="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl">Increase in valuation allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ValuationAllowancesAndReservesPeriodIncreaseDecrease" xlink:to="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl" xlink:title="label: ValuationAllowancesAndReservesPeriodIncreaseDecrease to us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl1" xml:lang="en-US" id="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl1">SEC Schedule, 12-09, Valuation Allowances and Reserves, Period Increase (Decrease)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ValuationAllowancesAndReservesPeriodIncreaseDecrease" xlink:to="us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl1" xlink:title="label: ValuationAllowancesAndReservesPeriodIncreaseDecrease to us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease_lbl1" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl">Shares used in computing diluted net loss per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1">Shares used in computing diluted net income per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl1" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2">Weighted Average Number of Shares Outstanding, Diluted</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfDilutedSharesOutstanding" xlink:to="us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" xlink:title="label: WeightedAverageNumberOfDilutedSharesOutstanding to us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_lbl2" />
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    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl">Shares used in computing basic net loss per share (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingBasic" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1">Weighted average shares outstanding (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="WeightedAverageNumberOfSharesOutstandingBasic" xlink:to="us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" xlink:title="label: WeightedAverageNumberOfSharesOutstandingBasic to us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:label="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" xlink:title="WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract" />
    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract_lbl">Shares (Denominator) [Abstract]</link:label>
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    <link:label xlink:type="resource" xlink:label="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl" xml:lang="en-US" id="us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract_lbl">Effect of Diluted Securities [Abstract]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ConsolidatedEntitiesAxis" xlink:label="ConsolidatedEntitiesAxis" xlink:title="ConsolidatedEntitiesAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesAxis" xlink:to="srt_ConsolidatedEntitiesAxis_lbl" xlink:title="label: ConsolidatedEntitiesAxis to srt_ConsolidatedEntitiesAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ConsolidatedEntitiesDomain" xlink:label="ConsolidatedEntitiesDomain" xlink:title="ConsolidatedEntitiesDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ConsolidatedEntitiesDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ConsolidatedEntitiesDomain_lbl" xml:lang="en-US" id="srt_ConsolidatedEntitiesDomain_lbl">Consolidated Entities [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConsolidatedEntitiesDomain" xlink:to="srt_ConsolidatedEntitiesDomain_lbl" xlink:title="label: ConsolidatedEntitiesDomain to srt_ConsolidatedEntitiesDomain_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ExecutiveOfficerMember" xlink:label="ExecutiveOfficerMember" xlink:title="ExecutiveOfficerMember" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember_lbl" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_ExecutiveOfficerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ExecutiveOfficerMember_lbl1" xml:lang="en-US" id="srt_ExecutiveOfficerMember_lbl1">Executive Officer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ExecutiveOfficerMember" xlink:to="srt_ExecutiveOfficerMember_lbl1" xlink:title="label: ExecutiveOfficerMember to srt_ExecutiveOfficerMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_LitigationCaseAxis" xlink:label="LitigationCaseAxis" xlink:title="LitigationCaseAxis" />
    <link:label xlink:type="resource" xlink:label="srt_LitigationCaseAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_LitigationCaseAxis_lbl" xml:lang="en-US" id="srt_LitigationCaseAxis_lbl">Litigation Case [Axis]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationCaseAxis" xlink:to="srt_LitigationCaseAxis_lbl" xlink:title="label: LitigationCaseAxis to srt_LitigationCaseAxis_lbl" />
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    <link:label xlink:type="resource" xlink:label="srt_LitigationCaseTypeDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_LitigationCaseTypeDomain_lbl" xml:lang="en-US" id="srt_LitigationCaseTypeDomain_lbl">Litigation Case [Domain]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LitigationCaseTypeDomain" xlink:to="srt_LitigationCaseTypeDomain_lbl" xlink:title="label: LitigationCaseTypeDomain to srt_LitigationCaseTypeDomain_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_MajorCustomersAxis" xlink:label="MajorCustomersAxis" xlink:title="MajorCustomersAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MajorCustomersAxis" xlink:to="srt_MajorCustomersAxis_lbl" xlink:title="label: MajorCustomersAxis to srt_MajorCustomersAxis_lbl" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember_lbl" xlink:title="label: MaximumMember to srt_MaximumMember_lbl" />
    <link:label xlink:type="resource" xlink:label="srt_MaximumMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_MaximumMember_lbl1" xml:lang="en-US" id="srt_MaximumMember_lbl1">Maximum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumMember" xlink:to="srt_MaximumMember_lbl1" xlink:title="label: MaximumMember to srt_MaximumMember_lbl1" />
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    <link:label xlink:type="resource" xlink:label="srt_MinimumMember_lbl" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="srt_MinimumMember_lbl" xml:lang="en-US" id="srt_MinimumMember_lbl">Minimum [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MinimumMember" xlink:to="srt_MinimumMember_lbl" xlink:title="label: MinimumMember to srt_MinimumMember_lbl" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_NameOfMajorCustomerDomain" xlink:label="NameOfMajorCustomerDomain" xlink:title="NameOfMajorCustomerDomain" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_OwnershipDomain" xlink:label="OwnershipDomain" xlink:title="OwnershipDomain" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_OwnershipAxis" xlink:label="OwnershipAxis" xlink:title="OwnershipAxis" />
    <link:label xlink:type="resource" xlink:label="srt_OwnershipAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_OwnershipAxis_lbl" xml:lang="en-US" id="srt_OwnershipAxis_lbl">Ownership [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductsAndServicesDomain" xlink:label="ProductsAndServicesDomain" xlink:title="ProductsAndServicesDomain" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ProductOrServiceAxis" xlink:label="ProductOrServiceAxis" xlink:title="ProductOrServiceAxis" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProductOrServiceAxis" xlink:to="srt_ProductOrServiceAxis_lbl" xlink:title="label: ProductOrServiceAxis to srt_ProductOrServiceAxis_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeAxis" xlink:label="RangeAxis" xlink:title="RangeAxis" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_RangeMember" xlink:label="RangeMember" xlink:title="RangeMember" />
    <link:label xlink:type="resource" xlink:label="srt_RangeMember_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_RangeMember_lbl" xml:lang="en-US" id="srt_RangeMember_lbl">Statistical Measurement [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ScenarioForecastMember" xlink:label="ScenarioForecastMember" xlink:title="ScenarioForecastMember" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_ScenarioUnspecifiedDomain" xlink:label="ScenarioUnspecifiedDomain" xlink:title="ScenarioUnspecifiedDomain" />
    <link:label xlink:type="resource" xlink:label="srt_ScenarioUnspecifiedDomain_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_ScenarioUnspecifiedDomain_lbl" xml:lang="en-US" id="srt_ScenarioUnspecifiedDomain_lbl">Scenario [Domain]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd#srt_StatementScenarioAxis" xlink:label="StatementScenarioAxis" xlink:title="StatementScenarioAxis" />
    <link:label xlink:type="resource" xlink:label="srt_StatementScenarioAxis_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="srt_StatementScenarioAxis_lbl" xml:lang="en-US" id="srt_StatementScenarioAxis_lbl">Scenario [Axis]</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CoverAbstract" xlink:label="CoverAbstract" xlink:title="CoverAbstract" />
    <link:label xlink:type="resource" xlink:label="dei_CoverAbstract_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CoverAbstract_lbl" xml:lang="en-US" id="dei_CoverAbstract_lbl">Cover [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CoverAbstract" xlink:to="dei_CoverAbstract_lbl" xlink:title="label: CoverAbstract to dei_CoverAbstract_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentType" xlink:label="DocumentType" xlink:title="DocumentType" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentType_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentType_lbl" xml:lang="en-US" id="dei_DocumentType_lbl">Document Type</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentAnnualReport" xlink:label="DocumentAnnualReport" xlink:title="DocumentAnnualReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentAnnualReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentAnnualReport_lbl" xml:lang="en-US" id="dei_DocumentAnnualReport_lbl">Document Annual Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentAnnualReport" xlink:to="dei_DocumentAnnualReport_lbl" xlink:title="label: DocumentAnnualReport to dei_DocumentAnnualReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentTransitionReport" xlink:label="DocumentTransitionReport" xlink:title="DocumentTransitionReport" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentTransitionReport_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentTransitionReport_lbl" xml:lang="en-US" id="dei_DocumentTransitionReport_lbl">Document Transition Report</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentTransitionReport" xlink:to="dei_DocumentTransitionReport_lbl" xlink:title="label: DocumentTransitionReport to dei_DocumentTransitionReport_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityInteractiveDataCurrent" xlink:label="EntityInteractiveDataCurrent" xlink:title="EntityInteractiveDataCurrent" />
    <link:label xlink:type="resource" xlink:label="dei_EntityInteractiveDataCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityInteractiveDataCurrent_lbl" xml:lang="en-US" id="dei_EntityInteractiveDataCurrent_lbl">Entity Interactive Data Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityInteractiveDataCurrent" xlink:to="dei_EntityInteractiveDataCurrent_lbl" xlink:title="label: EntityInteractiveDataCurrent to dei_EntityInteractiveDataCurrent_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AmendmentFlag" xlink:label="AmendmentFlag" xlink:title="AmendmentFlag" />
    <link:label xlink:type="resource" xlink:label="dei_AmendmentFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AmendmentFlag_lbl" xml:lang="en-US" id="dei_AmendmentFlag_lbl">Amendment Flag</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_IcfrAuditorAttestationFlag" xlink:label="IcfrAuditorAttestationFlag" xlink:title="IcfrAuditorAttestationFlag" />
    <link:label xlink:type="resource" xlink:label="dei_IcfrAuditorAttestationFlag_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_IcfrAuditorAttestationFlag_lbl" xml:lang="en-US" id="dei_IcfrAuditorAttestationFlag_lbl">ICFR Auditor Attestation Flag</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentFiscalYearFocus" xlink:label="DocumentFiscalYearFocus" xlink:title="DocumentFiscalYearFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalYearFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalYearFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalYearFocus_lbl">Document Fiscal Year Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalYearFocus" xlink:to="dei_DocumentFiscalYearFocus_lbl" xlink:title="label: DocumentFiscalYearFocus to dei_DocumentFiscalYearFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentFiscalPeriodFocus" xlink:label="DocumentFiscalPeriodFocus" xlink:title="DocumentFiscalPeriodFocus" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentFiscalPeriodFocus_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentFiscalPeriodFocus_lbl" xml:lang="en-US" id="dei_DocumentFiscalPeriodFocus_lbl">Document Fiscal Period Focus</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentFiscalPeriodFocus" xlink:to="dei_DocumentFiscalPeriodFocus_lbl" xlink:title="label: DocumentFiscalPeriodFocus to dei_DocumentFiscalPeriodFocus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentPeriodEndDate" xlink:label="DocumentPeriodEndDate" xlink:title="DocumentPeriodEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_DocumentPeriodEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_DocumentPeriodEndDate_lbl" xml:lang="en-US" id="dei_DocumentPeriodEndDate_lbl">Document Period End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DocumentPeriodEndDate" xlink:to="dei_DocumentPeriodEndDate_lbl" xlink:title="label: DocumentPeriodEndDate to dei_DocumentPeriodEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityRegistrantName" xlink:label="EntityRegistrantName" xlink:title="EntityRegistrantName" />
    <link:label xlink:type="resource" xlink:label="dei_EntityRegistrantName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityRegistrantName_lbl" xml:lang="en-US" id="dei_EntityRegistrantName_lbl">Entity Registrant Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityRegistrantName" xlink:to="dei_EntityRegistrantName_lbl" xlink:title="label: EntityRegistrantName to dei_EntityRegistrantName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCentralIndexKey" xlink:label="EntityCentralIndexKey" xlink:title="EntityCentralIndexKey" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFileNumber" xlink:label="EntityFileNumber" xlink:title="EntityFileNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFileNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFileNumber_lbl" xml:lang="en-US" id="dei_EntityFileNumber_lbl">Entity File Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFileNumber" xlink:to="dei_EntityFileNumber_lbl" xlink:title="label: EntityFileNumber to dei_EntityFileNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityTaxIdentificationNumber" xlink:label="EntityTaxIdentificationNumber" xlink:title="EntityTaxIdentificationNumber" />
    <link:label xlink:type="resource" xlink:label="dei_EntityTaxIdentificationNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityTaxIdentificationNumber_lbl" xml:lang="en-US" id="dei_EntityTaxIdentificationNumber_lbl">Entity Tax Identification Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityTaxIdentificationNumber" xlink:to="dei_EntityTaxIdentificationNumber_lbl" xlink:title="label: EntityTaxIdentificationNumber to dei_EntityTaxIdentificationNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="EntityIncorporationStateCountryCode" xlink:title="EntityIncorporationStateCountryCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityIncorporationStateCountryCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityIncorporationStateCountryCode_lbl" xml:lang="en-US" id="dei_EntityIncorporationStateCountryCode_lbl">Entity Incorporation, State or Country Code</link:label>
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CurrentFiscalYearEndDate" xlink:label="CurrentFiscalYearEndDate" xlink:title="CurrentFiscalYearEndDate" />
    <link:label xlink:type="resource" xlink:label="dei_CurrentFiscalYearEndDate_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CurrentFiscalYearEndDate_lbl" xml:lang="en-US" id="dei_CurrentFiscalYearEndDate_lbl">Current Fiscal Year End Date</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CurrentFiscalYearEndDate" xlink:to="dei_CurrentFiscalYearEndDate_lbl" xlink:title="label: CurrentFiscalYearEndDate to dei_CurrentFiscalYearEndDate_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityWellKnownSeasonedIssuer" xlink:label="EntityWellKnownSeasonedIssuer" xlink:title="EntityWellKnownSeasonedIssuer" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityWellKnownSeasonedIssuer" xlink:to="dei_EntityWellKnownSeasonedIssuer_lbl" xlink:title="label: EntityWellKnownSeasonedIssuer to dei_EntityWellKnownSeasonedIssuer_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityVoluntaryFilers" xlink:label="EntityVoluntaryFilers" xlink:title="EntityVoluntaryFilers" />
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    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCurrentReportingStatus" xlink:label="EntityCurrentReportingStatus" xlink:title="EntityCurrentReportingStatus" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCurrentReportingStatus" xlink:to="dei_EntityCurrentReportingStatus_lbl" xlink:title="label: EntityCurrentReportingStatus to dei_EntityCurrentReportingStatus_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityShellCompany" xlink:label="EntityShellCompany" xlink:title="EntityShellCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityShellCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityShellCompany_lbl" xml:lang="en-US" id="dei_EntityShellCompany_lbl">Entity Shell Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityShellCompany" xlink:to="dei_EntityShellCompany_lbl" xlink:title="label: EntityShellCompany to dei_EntityShellCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFilerCategory" xlink:label="EntityFilerCategory" xlink:title="EntityFilerCategory" />
    <link:label xlink:type="resource" xlink:label="dei_EntityFilerCategory_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityFilerCategory_lbl" xml:lang="en-US" id="dei_EntityFilerCategory_lbl">Entity Filer Category</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityFilerCategory" xlink:to="dei_EntityFilerCategory_lbl" xlink:title="label: EntityFilerCategory to dei_EntityFilerCategory_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntitySmallBusiness" xlink:label="EntitySmallBusiness" xlink:title="EntitySmallBusiness" />
    <link:label xlink:type="resource" xlink:label="dei_EntitySmallBusiness_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntitySmallBusiness_lbl" xml:lang="en-US" id="dei_EntitySmallBusiness_lbl">Entity Small Business</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntitySmallBusiness" xlink:to="dei_EntitySmallBusiness_lbl" xlink:title="label: EntitySmallBusiness to dei_EntitySmallBusiness_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityEmergingGrowthCompany" xlink:label="EntityEmergingGrowthCompany" xlink:title="EntityEmergingGrowthCompany" />
    <link:label xlink:type="resource" xlink:label="dei_EntityEmergingGrowthCompany_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityEmergingGrowthCompany_lbl" xml:lang="en-US" id="dei_EntityEmergingGrowthCompany_lbl">Entity Emerging Growth Company</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityEmergingGrowthCompany" xlink:to="dei_EntityEmergingGrowthCompany_lbl" xlink:title="label: EntityEmergingGrowthCompany to dei_EntityEmergingGrowthCompany_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityPublicFloat" xlink:label="EntityPublicFloat" xlink:title="EntityPublicFloat" />
    <link:label xlink:type="resource" xlink:label="dei_EntityPublicFloat_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityPublicFloat_lbl" xml:lang="en-US" id="dei_EntityPublicFloat_lbl">Entity Public Float</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityPublicFloat" xlink:to="dei_EntityPublicFloat_lbl" xlink:title="label: EntityPublicFloat to dei_EntityPublicFloat_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressAddressLine1" xlink:label="EntityAddressAddressLine1" xlink:title="EntityAddressAddressLine1" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressAddressLine1_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressAddressLine1_lbl" xml:lang="en-US" id="dei_EntityAddressAddressLine1_lbl">Entity Address, Address Line One</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressAddressLine1" xlink:to="dei_EntityAddressAddressLine1_lbl" xlink:title="label: EntityAddressAddressLine1 to dei_EntityAddressAddressLine1_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressCityOrTown" xlink:label="EntityAddressCityOrTown" xlink:title="EntityAddressCityOrTown" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressCityOrTown_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressCityOrTown_lbl" xml:lang="en-US" id="dei_EntityAddressCityOrTown_lbl">Entity Address, City or Town</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressCityOrTown" xlink:to="dei_EntityAddressCityOrTown_lbl" xlink:title="label: EntityAddressCityOrTown to dei_EntityAddressCityOrTown_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressStateOrProvince" xlink:label="EntityAddressStateOrProvince" xlink:title="EntityAddressStateOrProvince" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressStateOrProvince_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressStateOrProvince_lbl" xml:lang="en-US" id="dei_EntityAddressStateOrProvince_lbl">Entity Address, State or Province</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressStateOrProvince" xlink:to="dei_EntityAddressStateOrProvince_lbl" xlink:title="label: EntityAddressStateOrProvince to dei_EntityAddressStateOrProvince_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressPostalZipCode" xlink:label="EntityAddressPostalZipCode" xlink:title="EntityAddressPostalZipCode" />
    <link:label xlink:type="resource" xlink:label="dei_EntityAddressPostalZipCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityAddressPostalZipCode_lbl" xml:lang="en-US" id="dei_EntityAddressPostalZipCode_lbl">Entity Address, Postal Zip Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityAddressPostalZipCode" xlink:to="dei_EntityAddressPostalZipCode_lbl" xlink:title="label: EntityAddressPostalZipCode to dei_EntityAddressPostalZipCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CityAreaCode" xlink:label="CityAreaCode" xlink:title="CityAreaCode" />
    <link:label xlink:type="resource" xlink:label="dei_CityAreaCode_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_CityAreaCode_lbl" xml:lang="en-US" id="dei_CityAreaCode_lbl">City Area Code</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CityAreaCode" xlink:to="dei_CityAreaCode_lbl" xlink:title="label: CityAreaCode to dei_CityAreaCode_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_LocalPhoneNumber" xlink:label="LocalPhoneNumber" xlink:title="LocalPhoneNumber" />
    <link:label xlink:type="resource" xlink:label="dei_LocalPhoneNumber_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_LocalPhoneNumber_lbl" xml:lang="en-US" id="dei_LocalPhoneNumber_lbl">Local Phone Number</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LocalPhoneNumber" xlink:to="dei_LocalPhoneNumber_lbl" xlink:title="label: LocalPhoneNumber to dei_LocalPhoneNumber_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_Security12bTitle" xlink:label="Security12bTitle" xlink:title="Security12bTitle" />
    <link:label xlink:type="resource" xlink:label="dei_Security12bTitle_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_Security12bTitle_lbl" xml:lang="en-US" id="dei_Security12bTitle_lbl">Title of 12(b) Security</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Security12bTitle" xlink:to="dei_Security12bTitle_lbl" xlink:title="label: Security12bTitle to dei_Security12bTitle_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_TradingSymbol" xlink:label="TradingSymbol" xlink:title="TradingSymbol" />
    <link:label xlink:type="resource" xlink:label="dei_TradingSymbol_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_TradingSymbol_lbl" xml:lang="en-US" id="dei_TradingSymbol_lbl">Trading Symbol</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TradingSymbol" xlink:to="dei_TradingSymbol_lbl" xlink:title="label: TradingSymbol to dei_TradingSymbol_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SecurityExchangeName" xlink:label="SecurityExchangeName" xlink:title="SecurityExchangeName" />
    <link:label xlink:type="resource" xlink:label="dei_SecurityExchangeName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_SecurityExchangeName_lbl" xml:lang="en-US" id="dei_SecurityExchangeName_lbl">Security Exchange Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SecurityExchangeName" xlink:to="dei_SecurityExchangeName_lbl" xlink:title="label: SecurityExchangeName to dei_SecurityExchangeName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCommonStockSharesOutstanding" xlink:label="EntityCommonStockSharesOutstanding" xlink:title="EntityCommonStockSharesOutstanding" />
    <link:label xlink:type="resource" xlink:label="dei_EntityCommonStockSharesOutstanding_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_EntityCommonStockSharesOutstanding_lbl" xml:lang="en-US" id="dei_EntityCommonStockSharesOutstanding_lbl">Entity Common Stock, Shares Outstanding</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EntityCommonStockSharesOutstanding" xlink:to="dei_EntityCommonStockSharesOutstanding_lbl" xlink:title="label: EntityCommonStockSharesOutstanding to dei_EntityCommonStockSharesOutstanding_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AuditorName" xlink:label="AuditorName" xlink:title="AuditorName" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorName_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorName_lbl" xml:lang="en-US" id="dei_AuditorName_lbl">Auditor Name</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorName" xlink:to="dei_AuditorName_lbl" xlink:title="label: AuditorName to dei_AuditorName_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AuditorLocation" xlink:label="AuditorLocation" xlink:title="AuditorLocation" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorLocation_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorLocation_lbl" xml:lang="en-US" id="dei_AuditorLocation_lbl">Auditor Location</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorLocation" xlink:to="dei_AuditorLocation_lbl" xlink:title="label: AuditorLocation to dei_AuditorLocation_lbl" />
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AuditorFirmId" xlink:label="AuditorFirmId" xlink:title="AuditorFirmId" />
    <link:label xlink:type="resource" xlink:label="dei_AuditorFirmId_lbl" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="dei_AuditorFirmId_lbl" xml:lang="en-US" id="dei_AuditorFirmId_lbl">Auditor Firm ID</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AuditorFirmId" xlink:to="dei_AuditorFirmId_lbl" xlink:title="label: AuditorFirmId to dei_AuditorFirmId_lbl" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BicycleCollaborationMember" xlink:label="BicycleCollaborationMember" xlink:title="BicycleCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BicycleCollaborationMember_lbl" xml:lang="en-US" id="ions_BicycleCollaborationMember_lbl">Collaboration agreement entered into with Bicycle Therapeutics in December 2020, including an option to license Bicycle's peptide technology to potentially increase the delivery capabilities of the Company's Ligand Conjugated Antisense, or LICA, medicines.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember_lbl" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BicycleCollaborationMember_lbl1" xml:lang="en-US" id="ions_BicycleCollaborationMember_lbl1">Bicycle Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember_lbl1" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BicycleCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BicycleCollaborationMember_lbl2" xml:lang="en-US" id="ions_BicycleCollaborationMember_lbl2">Bicycle License Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BicycleCollaborationMember" xlink:to="ions_BicycleCollaborationMember_lbl2" xlink:title="label: BicycleCollaborationMember to ions_BicycleCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LockUpAgreementTermOfTradingRestriction" xlink:label="LockUpAgreementTermOfTradingRestriction" xlink:title="LockUpAgreementTermOfTradingRestriction" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LockUpAgreementTermOfTradingRestriction_lbl" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction_lbl">Period after completion of initial public offering by an equity investee and restriction to sell equity holding in the investee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction_lbl" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction_lbl1">Lock up Agreement, Term of Trading Restriction</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction_lbl1" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LockUpAgreementTermOfTradingRestriction_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LockUpAgreementTermOfTradingRestriction_lbl2" xml:lang="en-US" id="ions_LockUpAgreementTermOfTradingRestriction_lbl2">Trading restriction period under lock up agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LockUpAgreementTermOfTradingRestriction" xlink:to="ions_LockUpAgreementTermOfTradingRestriction_lbl2" xlink:title="label: LockUpAgreementTermOfTradingRestriction to ions_LockUpAgreementTermOfTradingRestriction_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CumulativePaymentsMade" xlink:label="CumulativePaymentsMade" xlink:title="CumulativePaymentsMade" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsMade_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsMade_lbl" xml:lang="en-US" id="ions_CumulativePaymentsMade_lbl">Cumulative amount of payments made under the collaboration agreement as of the end of the reporting period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsMade" xlink:to="ions_CumulativePaymentsMade_lbl" xlink:title="label: CumulativePaymentsMade to ions_CumulativePaymentsMade_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsMade_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsMade_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsMade_lbl1">Cumulative payments made</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsMade" xlink:to="ions_CumulativePaymentsMade_lbl1" xlink:title="label: CumulativePaymentsMade to ions_CumulativePaymentsMade_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsMade_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsMade_lbl2" xml:lang="en-US" id="ions_CumulativePaymentsMade_lbl2">Cumulative payments made</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsMade" xlink:to="ions_CumulativePaymentsMade_lbl2" xlink:title="label: CumulativePaymentsMade to ions_CumulativePaymentsMade_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_InvestmentInEquitySecuritiesFvNi" xlink:label="InvestmentInEquitySecuritiesFvNi" xlink:title="InvestmentInEquitySecuritiesFvNi" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_InvestmentInEquitySecuritiesFvNi_lbl" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi_lbl">Acquisition of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi_lbl" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi_lbl1">Investment in Equity Securities, FV-NI</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi_lbl1" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_InvestmentInEquitySecuritiesFvNi_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_InvestmentInEquitySecuritiesFvNi_lbl2" xml:lang="en-US" id="ions_InvestmentInEquitySecuritiesFvNi_lbl2">Equity investment</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="InvestmentInEquitySecuritiesFvNi" xlink:to="ions_InvestmentInEquitySecuritiesFvNi_lbl2" xlink:title="label: InvestmentInEquitySecuritiesFvNi to ions_InvestmentInEquitySecuritiesFvNi_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PaymentsMadeUnderCollaborationAgreement" xlink:label="PaymentsMadeUnderCollaborationAgreement" xlink:title="PaymentsMadeUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement_lbl">Represents the cash outflow for payments made under the collaboration agreement for the reimbursement of support received in connection with the Company's Huntington's disease program.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement_lbl" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement_lbl1">Payments made under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement_lbl1" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentsMadeUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentsMadeUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_PaymentsMadeUnderCollaborationAgreement_lbl2">Payment of license fee</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentsMadeUnderCollaborationAgreement" xlink:to="ions_PaymentsMadeUnderCollaborationAgreement_lbl2" xlink:title="label: PaymentsMadeUnderCollaborationAgreement to ions_PaymentsMadeUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" xlink:label="JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" xlink:title="JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" />
    <link:label xlink:type="resource" xlink:label="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl" xml:lang="en-US" id="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl">John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the "Delaware Action."</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" xlink:to="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl" xlink:title="label: JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember to ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl1" xml:lang="en-US" id="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl1">John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" xlink:to="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl1" xlink:title="label: JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember to ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl2" xml:lang="en-US" id="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl2">John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember" xlink:to="ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl2" xlink:title="label: JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember to ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:label="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:title="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl">The number of therapeutic targets granted to the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1">Number of therapeutic targets granted to partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl2">Number of therapeutic targets granted by Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl2" xlink:title="label: NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AlnylamCollaborationMember" xlink:label="AlnylamCollaborationMember" xlink:title="AlnylamCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamCollaborationMember_lbl" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl">Collaboration agreement entered into with Alnylam Pharmaceuticals, Inc. in March 2004 to develop and commercialize RNAi therapeutics.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamCollaborationMember_lbl1" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl1">Alnylam Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl1" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamCollaborationMember_lbl2" xml:lang="en-US" id="ions_AlnylamCollaborationMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamCollaborationMember" xlink:to="ions_AlnylamCollaborationMember_lbl2" xlink:title="label: AlnylamCollaborationMember to ions_AlnylamCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:label="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl">The number of unnamed therapeutic targets granted by the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1">Number of unnamed therapeutic targets granted by partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2">Number of unnamed therapeutic targets granted to Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xlink:title="label: NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:label="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:title="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl">The number of therapeutic targets granted by the partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1">Number of therapeutic targets granted by partner under collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2">Number of therapeutic targets granted to Ionis</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement" xlink:to="ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" xlink:title="label: NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement to ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfTherapeuticPrograms" xlink:label="NumberOfTherapeuticPrograms" xlink:title="NumberOfTherapeuticPrograms" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticPrograms_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTherapeuticPrograms_lbl" xml:lang="en-US" id="ions_NumberOfTherapeuticPrograms_lbl">The number of therapeutic programs with exclusive license rights under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticPrograms" xlink:to="ions_NumberOfTherapeuticPrograms_lbl" xlink:title="label: NumberOfTherapeuticPrograms to ions_NumberOfTherapeuticPrograms_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTherapeuticPrograms_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfTherapeuticPrograms_lbl1" xml:lang="en-US" id="ions_NumberOfTherapeuticPrograms_lbl1">Number of therapeutic programs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfTherapeuticPrograms" xlink:to="ions_NumberOfTherapeuticPrograms_lbl1" xlink:title="label: NumberOfTherapeuticPrograms to ions_NumberOfTherapeuticPrograms_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfMedicinesBeingDeveloped" xlink:label="NumberOfMedicinesBeingDeveloped" xlink:title="NumberOfMedicinesBeingDeveloped" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl">The number of medicines currently being developed under the collaboration agreement(s).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl1" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl1">Number of medicines being developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl1" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesBeingDeveloped_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMedicinesBeingDeveloped_lbl2" xml:lang="en-US" id="ions_NumberOfMedicinesBeingDeveloped_lbl2">Number of medicines currently being developed</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesBeingDeveloped" xlink:to="ions_NumberOfMedicinesBeingDeveloped_lbl2" xlink:title="label: NumberOfMedicinesBeingDeveloped to ions_NumberOfMedicinesBeingDeveloped_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl">Royalty percentage received on the net sales of each medicine from the collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1">Royalty percentage received on net sales of each medicine from collaboration partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl2">Royalty percentage received on net sales of each medicine from PTC</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner to ions_RoyaltyPercentageReceivedOnNetSalesOfEachMedicineFromCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PtcTherapeuticsCollaborationMember" xlink:label="PtcTherapeuticsCollaborationMember" xlink:title="PtcTherapeuticsCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PtcTherapeuticsCollaborationMember_lbl" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember_lbl">Exclusive license agreement entered into with PTC Therapeutics in August 2018 to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember_lbl" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PtcTherapeuticsCollaborationMember_lbl1" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember_lbl1">PTC Therapeutics Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember_lbl1" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PtcTherapeuticsCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_PtcTherapeuticsCollaborationMember_lbl2" xml:lang="en-US" id="ions_PtcTherapeuticsCollaborationMember_lbl2">PTC Therapeutics [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PtcTherapeuticsCollaborationMember" xlink:to="ions_PtcTherapeuticsCollaborationMember_lbl2" xlink:title="label: PtcTherapeuticsCollaborationMember to ions_PtcTherapeuticsCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:label="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:title="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl">The potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl1" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl1">Potential premium received if common stock is purchased in future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl1" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xml:lang="en-US" id="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2">Potential premium received if common stock is purchased in the future</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture" xlink:to="ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" xlink:title="label: PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture to ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PremiumReceivedOnSharesIssued" xlink:label="PremiumReceivedOnSharesIssued" xlink:title="PremiumReceivedOnSharesIssued" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl">The total amount of the premium received over the trading price of common stock at the time of purchase.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl1" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl1">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl1" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumReceivedOnSharesIssued_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumReceivedOnSharesIssued_lbl2" xml:lang="en-US" id="ions_PremiumReceivedOnSharesIssued_lbl2">Premium received on shares issued</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumReceivedOnSharesIssued" xlink:to="ions_PremiumReceivedOnSharesIssued_lbl2" xlink:title="label: PremiumReceivedOnSharesIssued to ions_PremiumReceivedOnSharesIssued_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PelacarsenActivePharmaceuticalIngredientMember" xlink:label="PelacarsenActivePharmaceuticalIngredientMember" xlink:title="PelacarsenActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl">The active pharmaceutical ingredient, or API, for Pelacarsen, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1">Pelacarsen Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl2" xml:lang="en-US" id="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl2">Pelacarsen API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenActivePharmaceuticalIngredientMember" xlink:to="ions_PelacarsenActivePharmaceuticalIngredientMember_lbl2" xlink:title="label: PelacarsenActivePharmaceuticalIngredientMember to ions_PelacarsenActivePharmaceuticalIngredientMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ResearchAndDevelopmentServicesForOlezarsenMember" xlink:label="ResearchAndDevelopmentServicesForOlezarsenMember" xlink:title="ResearchAndDevelopmentServicesForOlezarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl">Research and development (R&amp;D) services for olezarsen, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForOlezarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForOlezarsenMember to ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl1">Research and Development Services for Olezarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForOlezarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForOlezarsenMember to ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl2">R&amp;D Services for Olezarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForOlezarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForOlezarsenMember to ions_ResearchAndDevelopmentServicesForOlezarsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_OlezarsenActivePharmaceuticalIngredientMember" xlink:label="OlezarsenActivePharmaceuticalIngredientMember" xlink:title="OlezarsenActivePharmaceuticalIngredientMember" />
    <link:label xlink:type="resource" xlink:label="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl" xml:lang="en-US" id="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl">The active pharmaceutical ingredient, or API, for Olezarsen, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein ApoCIII.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OlezarsenActivePharmaceuticalIngredientMember" xlink:to="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl" xlink:title="label: OlezarsenActivePharmaceuticalIngredientMember to ions_OlezarsenActivePharmaceuticalIngredientMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl1" xml:lang="en-US" id="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl1">Olezarsen Active Pharmaceutical Ingredient [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OlezarsenActivePharmaceuticalIngredientMember" xlink:to="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl1" xlink:title="label: OlezarsenActivePharmaceuticalIngredientMember to ions_OlezarsenActivePharmaceuticalIngredientMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl2" xml:lang="en-US" id="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl2">Olezarsen API [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OlezarsenActivePharmaceuticalIngredientMember" xlink:to="ions_OlezarsenActivePharmaceuticalIngredientMember_lbl2" xlink:title="label: OlezarsenActivePharmaceuticalIngredientMember to ions_OlezarsenActivePharmaceuticalIngredientMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RoyaltyPercentageReceivedOnSalesOfMedicine" xlink:label="RoyaltyPercentageReceivedOnSalesOfMedicine" xlink:title="RoyaltyPercentageReceivedOnSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl">Royalty percentage received on the sales of a medicine by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicine to ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl1">Royalty percentage received on sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicine to ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl2">Royalty percentage received on sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicine to ions_RoyaltyPercentageReceivedOnSalesOfMedicine_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:label="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:title="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl">The cash inflow from the sale of common stock, including the premium paid for the purchase of common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1">Proceeds from sale of common stock, including premium paid</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xml:lang="en-US" id="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2">Proceeds from sale of common stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ProceedsFromSaleOfCommonStockIncludingPremiumPaid" xlink:to="ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" xlink:title="label: ProceedsFromSaleOfCommonStockIncludingPremiumPaid to ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ResearchAndDevelopmentServicesForPelacarsenMember" xlink:label="ResearchAndDevelopmentServicesForPelacarsenMember" xlink:title="ResearchAndDevelopmentServicesForPelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl">Research and development (R&amp;D) services for Pelacarsen, an antisense therapy with the potential to significantly reduce cardiovascular risk in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForPelacarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl" xlink:title="label: ResearchAndDevelopmentServicesForPelacarsenMember to ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl1">Research and Development Services for Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForPelacarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl1" xlink:title="label: ResearchAndDevelopmentServicesForPelacarsenMember to ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl2">R&amp;D Services for Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentServicesForPelacarsenMember" xlink:to="ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl2" xlink:title="label: ResearchAndDevelopmentServicesForPelacarsenMember to ions_ResearchAndDevelopmentServicesForPelacarsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PercentageEnrollmentInPhase3Study" xlink:label="PercentageEnrollmentInPhase3Study" xlink:title="PercentageEnrollmentInPhase3Study" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageEnrollmentInPhase3Study_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageEnrollmentInPhase3Study_lbl" xml:lang="en-US" id="ions_PercentageEnrollmentInPhase3Study_lbl">Percentage enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageEnrollmentInPhase3Study" xlink:to="ions_PercentageEnrollmentInPhase3Study_lbl" xlink:title="label: PercentageEnrollmentInPhase3Study to ions_PercentageEnrollmentInPhase3Study_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageEnrollmentInPhase3Study_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageEnrollmentInPhase3Study_lbl1" xml:lang="en-US" id="ions_PercentageEnrollmentInPhase3Study_lbl1">Percentage enrollment in Phase 3 study</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageEnrollmentInPhase3Study" xlink:to="ions_PercentageEnrollmentInPhase3Study_lbl1" xlink:title="label: PercentageEnrollmentInPhase3Study to ions_PercentageEnrollmentInPhase3Study_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageEnrollmentInPhase3Study_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageEnrollmentInPhase3Study_lbl2" xml:lang="en-US" id="ions_PercentageEnrollmentInPhase3Study_lbl2">Percentage enrollment in Lp(a) HORIZON Phase 3 cardiovascular outcome study</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageEnrollmentInPhase3Study" xlink:to="ions_PercentageEnrollmentInPhase3Study_lbl2" xlink:title="label: PercentageEnrollmentInPhase3Study to ions_PercentageEnrollmentInPhase3Study_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:label="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:title="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in July 2015 to discover and develop antisense therapies for treating cardiovascular and metabolic diseases primarily focused on targets in the kidney and renal diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1">AstraZeneca Collaboration, Cardiovascular, Renal and Metabolic Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl2" xml:lang="en-US" id="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl2">Cardiovascular, Renal and Metabolic Diseases Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember" xlink:to="ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl2" xlink:title="label: AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember to ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:label="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:title="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl">Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1">Percentage of costs associated with ongoing global Phase 3 development program paid by Collaboration Partner</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xml:lang="en-US" id="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner" xlink:to="ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" xlink:title="label: PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner to ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfMaterialComponents" xlink:label="NumberOfMaterialComponents" xlink:title="NumberOfMaterialComponents" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMaterialComponents_lbl" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl">The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMaterialComponents_lbl1" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl1">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl1" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMaterialComponents_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMaterialComponents_lbl2" xml:lang="en-US" id="ions_NumberOfMaterialComponents_lbl2">Number of material components</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMaterialComponents" xlink:to="ions_NumberOfMaterialComponents_lbl2" xlink:title="label: NumberOfMaterialComponents to ions_NumberOfMaterialComponents_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:label="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:title="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl">Royalty percentage received on sales of a medicine in the United States by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1">Royalty percentage received on sales of medicine in United States</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl2">Royalty percentage received on sales of medicine in U.S.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates" xlink:to="ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates to ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" xlink:label="MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" xlink:title="MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl">The maximum amount of license fees to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl1">Maximum amount of license fees per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl2">Maximum amount of license fees per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:label="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:title="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl">Cumulative amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1">Cumulative Revenue from Contract with Customer, Excluding Assessed Tax</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xml:lang="en-US" id="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2">Cumulative revenue earned</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativeRevenueFromContractWithCustomerExcludingAssessedTax" xlink:to="ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" xlink:title="label: CumulativeRevenueFromContractWithCustomerExcludingAssessedTax to ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2">Maximum amount of regulatory milestone payments per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:label="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:title="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xml:lang="en-US" id="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl">Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:title="label: CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation to ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1">Cumulative payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:title="label: CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation to ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xml:lang="en-US" id="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2">Cumulative payments included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:title="label: CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation to ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_TermOfCollaborationAgreement" xlink:label="TermOfCollaborationAgreement" xlink:title="TermOfCollaborationAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TermOfCollaborationAgreement_lbl" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl">Term of the collaboration agreement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TermOfCollaborationAgreement_lbl1" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl1">Term of collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl1" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TermOfCollaborationAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TermOfCollaborationAgreement_lbl2" xml:lang="en-US" id="ions_TermOfCollaborationAgreement_lbl2">Term of collaboration agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TermOfCollaborationAgreement" xlink:to="ions_TermOfCollaborationAgreement_lbl2" xlink:title="label: TermOfCollaborationAgreement to ions_TermOfCollaborationAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_UpfrontPaymentReceived" xlink:label="UpfrontPaymentReceived" xlink:title="UpfrontPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl">The amount of upfront payments received during the period under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl1">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl1" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceived_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceived_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceived" xlink:to="ions_UpfrontPaymentReceived_lbl2" xlink:title="label: UpfrontPaymentReceived to ions_UpfrontPaymentReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:label="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:title="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl">Collaboration agreement entered into with Biogen Inc. in December 2017 to identify new antisense oligonucleotide drug candidates for the treatment of spinal muscular atrophy, or SMA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1">Biogen Collaboration, New Antisense Medicines for Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2">New Antisense Medicines for the Treatment of SMA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember" xlink:to="ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" xlink:title="label: BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember to ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaborationSpinrazaMember" xlink:label="BiogenCollaborationSpinrazaMember" xlink:title="BiogenCollaborationSpinrazaMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationSpinrazaMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember_lbl">Collaboration agreement entered into with Biogen Inc. in January 2012 to develop and commercialize nusinersen for the treatment of spinal muscular atrophy, or SMA, a severe motor-neuron disease that is the leading genetic cause of infant mortality.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember_lbl" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationSpinrazaMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember_lbl1">Biogen Collaboration, Spinraza [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember_lbl1" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationSpinrazaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationSpinrazaMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationSpinrazaMember_lbl2">SPINRAZA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationSpinrazaMember" xlink:to="ions_BiogenCollaborationSpinrazaMember_lbl2" xlink:title="label: BiogenCollaborationSpinrazaMember to ions_BiogenCollaborationSpinrazaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaboration2013StrategicNeurologyMember" xlink:label="BiogenCollaboration2013StrategicNeurologyMember" xlink:title="BiogenCollaboration2013StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in September 2013 focused on applying antisense technology to advance the treatment of neurodegenerative diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1">Biogen Collaboration, 2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2">2013 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2013StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2013StrategicNeurologyMember to ions_BiogenCollaboration2013StrategicNeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaboration2018StrategicNeurologyMember" xlink:label="BiogenCollaboration2018StrategicNeurologyMember" xlink:title="BiogenCollaboration2018StrategicNeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl">Collaboration agreement entered into with Biogen Inc. in April 2018 to develop novel antisense drug candidates for a broad range of neurological diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1">Biogen Collaboration, 2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2">2018 Strategic Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2018StrategicNeurologyMember" xlink:to="ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2018StrategicNeurologyMember to ions_BiogenCollaboration2018StrategicNeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaboration2012NeurologyMember" xlink:label="BiogenCollaboration2012NeurologyMember" xlink:title="BiogenCollaboration2012NeurologyMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl">Collaborative agreement entered into with Biogen Inc. in December 2012 focused on developing and commercializing novel antisense drugs for up to three targets to treat neurological or neuromuscular diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl1">Biogen Collaboration, 2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl1" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaboration2012NeurologyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaboration2012NeurologyMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaboration2012NeurologyMember_lbl2">2012 Neurology [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaboration2012NeurologyMember" xlink:to="ions_BiogenCollaboration2012NeurologyMember_lbl2" xlink:title="label: BiogenCollaboration2012NeurologyMember to ions_BiogenCollaboration2012NeurologyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl1">Maximum amount of payments receivable per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl2">Maximum amount of payments receivable per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:label="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:title="UpfrontPaymentReceivedIncludingPurchaseOfStock" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl">The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1">Upfront payment received, including purchase of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xml:lang="en-US" id="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2">Upfront payment received, including purchase of stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontPaymentReceivedIncludingPurchaseOfStock" xlink:to="ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" xlink:title="label: UpfrontPaymentReceivedIncludingPurchaseOfStock to ions_UpfrontPaymentReceivedIncludingPurchaseOfStock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" xlink:label="NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" xlink:title="NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl">The number of programs under which medicines are to be developed and commercialized under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl" xlink:title="label: NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl1" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl1">Number of programs under which medicines are to be developed and commercialized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl1" xlink:title="label: NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl2" xml:lang="en-US" id="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl2">Number of programs under which medicines are to be developed and commercialized</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized" xlink:to="ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl2" xlink:title="label: NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized to ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2">Maximum amount of development milestone payments per antisense molecule over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PremiumPaidOnSharesPurchased" xlink:label="PremiumPaidOnSharesPurchased" xlink:title="PremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl">The cash premium paid on the purchase of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl1">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PremiumPaidOnSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PremiumPaidOnSharesPurchased_lbl2" xml:lang="en-US" id="ions_PremiumPaidOnSharesPurchased_lbl2">Premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PremiumPaidOnSharesPurchased" xlink:to="ions_PremiumPaidOnSharesPurchased_lbl2" xlink:title="label: PremiumPaidOnSharesPurchased to ions_PremiumPaidOnSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfMedicinesCurrentlyBeingAdvanced" xlink:label="NumberOfMedicinesCurrentlyBeingAdvanced" xlink:title="NumberOfMedicinesCurrentlyBeingAdvanced" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl">The number of medicines currently being advanced under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyBeingAdvanced" xlink:to="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl" xlink:title="label: NumberOfMedicinesCurrentlyBeingAdvanced to ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl1" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl1">Number of medicines currently being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyBeingAdvanced" xlink:to="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl1" xlink:title="label: NumberOfMedicinesCurrentlyBeingAdvanced to ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl2" xml:lang="en-US" id="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl2">Number of medicines currently being advanced</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfMedicinesCurrentlyBeingAdvanced" xlink:to="ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl2" xlink:title="label: NumberOfMedicinesCurrentlyBeingAdvanced to ions_NumberOfMedicinesCurrentlyBeingAdvanced_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PercentageCashPremiumPaidOnSharesPurchased" xlink:label="PercentageCashPremiumPaidOnSharesPurchased" xlink:title="PercentageCashPremiumPaidOnSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl">The percentage cash premium paid per share of the Company's common stock under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xml:lang="en-US" id="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2">Percentage cash premium paid on shares purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageCashPremiumPaidOnSharesPurchased" xlink:to="ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" xlink:title="label: PercentageCashPremiumPaidOnSharesPurchased to ions_PercentageCashPremiumPaidOnSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MedicinesForMultipleSystemAtrophyMember" xlink:label="MedicinesForMultipleSystemAtrophyMember" xlink:title="MedicinesForMultipleSystemAtrophyMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl">Medicines to treat multiple system atrophy (MSA), a progressive neurodegenerative disorder characterized by a combination of symptoms that affect both the autonomic nervous system and movement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl1">Medicines for Multiple System Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl1" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xml:lang="en-US" id="ions_MedicinesForMultipleSystemAtrophyMember_lbl2">Medicines for Multiple System Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForMultipleSystemAtrophyMember" xlink:to="ions_MedicinesForMultipleSystemAtrophyMember_lbl2" xlink:title="label: MedicinesForMultipleSystemAtrophyMember to ions_MedicinesForMultipleSystemAtrophyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MedicinesForParkinsonsDiseaseMember" xlink:label="MedicinesForParkinsonsDiseaseMember" xlink:title="MedicinesForParkinsonsDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForParkinsonsDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForParkinsonsDiseaseMember_lbl" xml:lang="en-US" id="ions_MedicinesForParkinsonsDiseaseMember_lbl">Medicines to treat Parkinson's disease, a disorder of the central nervous system that affects movement, often including tremors.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForParkinsonsDiseaseMember" xlink:to="ions_MedicinesForParkinsonsDiseaseMember_lbl" xlink:title="label: MedicinesForParkinsonsDiseaseMember to ions_MedicinesForParkinsonsDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForParkinsonsDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForParkinsonsDiseaseMember_lbl1" xml:lang="en-US" id="ions_MedicinesForParkinsonsDiseaseMember_lbl1">Medicines for Parkinson's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForParkinsonsDiseaseMember" xlink:to="ions_MedicinesForParkinsonsDiseaseMember_lbl1" xlink:title="label: MedicinesForParkinsonsDiseaseMember to ions_MedicinesForParkinsonsDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForParkinsonsDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForParkinsonsDiseaseMember_lbl2" xml:lang="en-US" id="ions_MedicinesForParkinsonsDiseaseMember_lbl2">Medicines for Parkinson's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForParkinsonsDiseaseMember" xlink:to="ions_MedicinesForParkinsonsDiseaseMember_lbl2" xlink:title="label: MedicinesForParkinsonsDiseaseMember to ions_MedicinesForParkinsonsDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_Ion582Member" xlink:label="Ion582Member" xlink:title="Ion582Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion582Member_lbl" xml:lang="en-US" id="ions_Ion582Member_lbl">ION582 is an antisense investigational medicine that targets Ubiquitin Protein Ligase E3A-Antisense Transcript (UBE3A-ATS), which is a long non-coding ribonucleic acid (lncRNA).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl" xlink:title="label: Ion582Member to ions_Ion582Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion582Member_lbl1" xml:lang="en-US" id="ions_Ion582Member_lbl1">Ion582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl1" xlink:title="label: Ion582Member to ions_Ion582Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion582Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion582Member_lbl2" xml:lang="en-US" id="ions_Ion582Member_lbl2">ION582 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion582Member" xlink:to="ions_Ion582Member_lbl2" xlink:title="label: Ion582Member to ions_Ion582Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MedicinesForAmyotrophicLateralSclerosisMember" xlink:label="MedicinesForAmyotrophicLateralSclerosisMember" xlink:title="MedicinesForAmyotrophicLateralSclerosisMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl" xml:lang="en-US" id="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl">Medicines to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, a nervous system disease that weakens muscles and impacts physical function.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForAmyotrophicLateralSclerosisMember" xlink:to="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl" xlink:title="label: MedicinesForAmyotrophicLateralSclerosisMember to ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl1" xml:lang="en-US" id="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl1">Medicines for Amyotrophic Lateral Sclerosis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForAmyotrophicLateralSclerosisMember" xlink:to="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl1" xlink:title="label: MedicinesForAmyotrophicLateralSclerosisMember to ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl2" xml:lang="en-US" id="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl2">Medicines for ALS [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForAmyotrophicLateralSclerosisMember" xlink:to="ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl2" xlink:title="label: MedicinesForAmyotrophicLateralSclerosisMember to ions_MedicinesForAmyotrophicLateralSclerosisMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1">Maximum amount of payments receivable per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl2">Maximum amount of payments receivable per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MedicinesForUndisclosedTargetsMember" xlink:label="MedicinesForUndisclosedTargetsMember" xlink:title="MedicinesForUndisclosedTargetsMember" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl">Medicines to treat undisclosed targets under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl1" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl1">Medicines for Undisclosed Targets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl1" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MedicinesForUndisclosedTargetsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MedicinesForUndisclosedTargetsMember_lbl2" xml:lang="en-US" id="ions_MedicinesForUndisclosedTargetsMember_lbl2">Medicines for Undisclosed Targets [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MedicinesForUndisclosedTargetsMember" xlink:to="ions_MedicinesForUndisclosedTargetsMember_lbl2" xlink:title="label: MedicinesForUndisclosedTargetsMember to ions_MedicinesForUndisclosedTargetsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_TofersenMember" xlink:label="TofersenMember" xlink:title="TofersenMember" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TofersenMember_lbl" xml:lang="en-US" id="ions_TofersenMember_lbl">Tofersen (IONIS-SOD1Rx or BIIB067) is an antisense medicine designed to inhibit the production of superoxide dismutase 1, or SOD1, which is a well understood genetic cause of familial amyotrophic lateral sclerosis, or ALS.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl" xlink:title="label: TofersenMember to ions_TofersenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TofersenMember_lbl1" xml:lang="en-US" id="ions_TofersenMember_lbl1">Tofersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl1" xlink:title="label: TofersenMember to ions_TofersenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TofersenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TofersenMember_lbl2" xml:lang="en-US" id="ions_TofersenMember_lbl2">Tofersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TofersenMember" xlink:to="ions_TofersenMember_lbl2" xlink:title="label: TofersenMember to ions_TofersenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl">The maximum amount of license fees to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of license fees per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl2">Maximum amount of license fees per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2">Maximum amount of regulatory milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2">Maximum amount of development milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_Ion306Member" xlink:label="Ion306Member" xlink:title="Ion306Member" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_Ion306Member_lbl" xml:lang="en-US" id="ions_Ion306Member_lbl">ION306 is an antisense oligonucleotide or ASO that is designed to boost production of the survival motor neuron protein, known as SMN.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl" xlink:title="label: Ion306Member to ions_Ion306Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_Ion306Member_lbl1" xml:lang="en-US" id="ions_Ion306Member_lbl1">Ion306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl1" xlink:title="label: Ion306Member to ions_Ion306Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_Ion306Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_Ion306Member_lbl2" xml:lang="en-US" id="ions_Ion306Member_lbl2">ION306 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="Ion306Member" xlink:to="ions_Ion306Member_lbl2" xlink:title="label: Ion306Member to ions_Ion306Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" xlink:label="MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" xlink:title="MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl" xml:lang="en-US" id="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl">Milestone payments achieved under the collaboration agreement during the period and included in the transaction price for the performance obligation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl" xlink:title="label: MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation to ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl1" xml:lang="en-US" id="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl1">Milestone payments achieved and included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl1" xlink:title="label: MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation to ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl2" xml:lang="en-US" id="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl2">Milestone payments achieved and included in transaction price for performance obligation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation" xlink:to="ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl2" xlink:title="label: MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation to ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IonisMaptMember" xlink:label="IonisMaptMember" xlink:title="IonisMaptMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisMaptMember_lbl" xml:lang="en-US" id="ions_IonisMaptMember_lbl">IONIS-MAPT is an antisense drug designed to selectively reduce the production of microtubule-associated protein tau (MAPT), or tau protein, in the brain, for the treatment of Alzheimer's disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IonisMaptMember_lbl1" xml:lang="en-US" id="ions_IonisMaptMember_lbl1">Ionis-Mapt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl1" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IonisMaptMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IonisMaptMember_lbl2" xml:lang="en-US" id="ions_IonisMaptMember_lbl2">IONIS-MAPT [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IonisMaptMember" xlink:to="ions_IonisMaptMember_lbl2" xlink:title="label: IonisMaptMember to ions_IonisMaptMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RocheCollaborationHuntingtonsDiseaseMember" xlink:label="RocheCollaborationHuntingtonsDiseaseMember" xlink:title="RocheCollaborationHuntingtonsDiseaseMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in April 2013 to develop treatments for Huntington's disease, or HD, based on the Company's antisense technology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1">Roche Collaboration, Huntington's Disease [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2">Collaboration to Develop Treatments for Huntington's Disease with Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationHuntingtonsDiseaseMember" xlink:to="ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" xlink:title="label: RocheCollaborationHuntingtonsDiseaseMember to ions_RocheCollaborationHuntingtonsDiseaseMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:label="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:title="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl">Collaboration agreement entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche, in October 2018 to develop IONIS-FB-L for the treatment of complement-mediated diseases.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1">Roche Collaboration, Ionis-Fb-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2">IONIS-FB-L for Complement-Mediated Diseases [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationIonisFbLForComplementMediatedDiseasesMember" xlink:to="ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" xlink:title="label: RocheCollaborationIonisFbLForComplementMediatedDiseasesMember to ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of sales milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of sales milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl2">Maximum amount of sales milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NextPaymentToBeAchieved" xlink:label="NextPaymentToBeAchieved" xlink:title="NextPaymentToBeAchieved" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NextPaymentToBeAchieved_lbl" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl">The next payment to be achieved under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NextPaymentToBeAchieved_lbl1" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl1">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl1" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NextPaymentToBeAchieved_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NextPaymentToBeAchieved_lbl2" xml:lang="en-US" id="ions_NextPaymentToBeAchieved_lbl2">Next payment to be achieved</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NextPaymentToBeAchieved" xlink:to="ions_NextPaymentToBeAchieved_lbl2" xlink:title="label: NextPaymentToBeAchieved to ions_NextPaymentToBeAchieved_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:label="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:title="MaximumAmountOfLicenseFeesOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl">The maximum amount of license fees to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1">Maximum amount of license fees over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl2">Maximum amount of license fees over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfLicenseFeesOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfLicenseFeesOverTermOfCollaboration to ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of development milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl2">Maximum amount of development milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:label="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:title="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl">The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl2">Maximum amount of payments receivable over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfPaymentsReceivableOverTermOfCollaboration to ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl">The maximum amount of upfront payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl2">Maximum amount of upfront payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration to ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:label="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:title="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl">The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl2">Maximum amount of regulatory milestone payments over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration to ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CumulativePaymentsReceived" xlink:label="CumulativePaymentsReceived" xlink:title="CumulativePaymentsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CumulativePaymentsReceived_lbl" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl">Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CumulativePaymentsReceived_lbl1" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl1">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl1" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CumulativePaymentsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CumulativePaymentsReceived_lbl2" xml:lang="en-US" id="ions_CumulativePaymentsReceived_lbl2">Cumulative payments received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CumulativePaymentsReceived" xlink:to="ions_CumulativePaymentsReceived_lbl2" xlink:title="label: CumulativePaymentsReceived to ions_CumulativePaymentsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:label="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:title="RoyaltyPercentageReceivedOnNetSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl">Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xml:lang="en-US" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2">Royalty percentage received on net sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RoyaltyPercentageReceivedOnNetSalesOfMedicine" xlink:to="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" xlink:title="label: RoyaltyPercentageReceivedOnNetSalesOfMedicine to ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:label="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:title="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl">The maximum amount of milestone payments to be received for each medicine that is successfully developed over the term of the collaboration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1">Maximum amount of milestone payments per medicine over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xml:lang="en-US" id="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2">Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration" xlink:to="ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" xlink:title="label: MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration to ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:label="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:title="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl">The number of separate performance obligations under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1">Revenue from Contract with Customer, Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2">Number of separate performance obligations</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations" xlink:to="ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" xlink:title="label: RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations to ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RevenueFromContractWithCustomerTransactionPrice" xlink:label="RevenueFromContractWithCustomerTransactionPrice" xlink:title="RevenueFromContractWithCustomerTransactionPrice" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl">The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1">Revenue from Contract with Customer, Transaction Price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xml:lang="en-US" id="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2">Transaction price</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RevenueFromContractWithCustomerTransactionPrice" xlink:to="ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" xlink:title="label: RevenueFromContractWithCustomerTransactionPrice to ions_RevenueFromContractWithCustomerTransactionPrice_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ImmunoglobulinANephropathyMember" xlink:label="ImmunoglobulinANephropathyMember" xlink:title="ImmunoglobulinANephropathyMember" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl">Immunoglobulin A nephropathy (IgAN) is a chronic kidney disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl1" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl1">Immunoglobulin A Nephropathy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl1" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ImmunoglobulinANephropathyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ImmunoglobulinANephropathyMember_lbl2" xml:lang="en-US" id="ions_ImmunoglobulinANephropathyMember_lbl2">IgAN [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ImmunoglobulinANephropathyMember" xlink:to="ions_ImmunoglobulinANephropathyMember_lbl2" xlink:title="label: ImmunoglobulinANephropathyMember to ions_ImmunoglobulinANephropathyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_GeographicAtrophyMember" xlink:label="GeographicAtrophyMember" xlink:title="GeographicAtrophyMember" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GeographicAtrophyMember_lbl" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl">Geographic Atrophy (GA) is the advanced stage of advanced aged-related macular degeneration (AMD).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GeographicAtrophyMember_lbl1" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl1">Geographic Atrophy [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl1" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GeographicAtrophyMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GeographicAtrophyMember_lbl2" xml:lang="en-US" id="ions_GeographicAtrophyMember_lbl2">GA [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GeographicAtrophyMember" xlink:to="ions_GeographicAtrophyMember_lbl2" xlink:title="label: GeographicAtrophyMember to ions_GeographicAtrophyMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfDiseaseIndications" xlink:label="NumberOfDiseaseIndications" xlink:title="NumberOfDiseaseIndications" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfDiseaseIndications_lbl" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl">Number of disease indications for which studies are currently being conducted under the collaboration agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfDiseaseIndications_lbl1" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl1">Number of disease indications</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl1" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfDiseaseIndications_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfDiseaseIndications_lbl2" xml:lang="en-US" id="ions_NumberOfDiseaseIndications_lbl2">Number of disease indications</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfDiseaseIndications" xlink:to="ions_NumberOfDiseaseIndications_lbl2" xlink:title="label: NumberOfDiseaseIndications to ions_NumberOfDiseaseIndications_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AstrazenecaCollaborationsMember" xlink:label="AstrazenecaCollaborationsMember" xlink:title="AstrazenecaCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationsMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl">Collaboration agreements entered into with AstraZeneca PLC.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationsMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl1">AstraZeneca Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl1" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationsMember_lbl2" xml:lang="en-US" id="ions_AstrazenecaCollaborationsMember_lbl2">AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationsMember" xlink:to="ions_AstrazenecaCollaborationsMember_lbl2" xlink:title="label: AstrazenecaCollaborationsMember to ions_AstrazenecaCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BiogenCollaborationsMember" xlink:label="BiogenCollaborationsMember" xlink:title="BiogenCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BiogenCollaborationsMember_lbl" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl">Collaboration agreements entered into with Biogen Inc.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BiogenCollaborationsMember_lbl1" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl1">Biogen Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl1" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BiogenCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BiogenCollaborationsMember_lbl2" xml:lang="en-US" id="ions_BiogenCollaborationsMember_lbl2">Biogen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BiogenCollaborationsMember" xlink:to="ions_BiogenCollaborationsMember_lbl2" xlink:title="label: BiogenCollaborationsMember to ions_BiogenCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RocheCollaborationsMember" xlink:label="RocheCollaborationsMember" xlink:title="RocheCollaborationsMember" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_RocheCollaborationsMember_lbl" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl">Collaboration agreements entered into with Hoffman-La Roche Inc. and F. Hoffmann-La Roche Ltd., collectively Roche.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_RocheCollaborationsMember_lbl1" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl1">Roche Collaborations [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl1" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_RocheCollaborationsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_RocheCollaborationsMember_lbl2" xml:lang="en-US" id="ions_RocheCollaborationsMember_lbl2">Roche [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="RocheCollaborationsMember" xlink:to="ions_RocheCollaborationsMember_lbl2" xlink:title="label: RocheCollaborationsMember to ions_RocheCollaborationsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_GlaxoSmithKlineCollaborationMember" xlink:label="GlaxoSmithKlineCollaborationMember" xlink:title="GlaxoSmithKlineCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GlaxoSmithKlineCollaborationMember_lbl" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember_lbl">Collaboration agreement entered into with GlaxoSmithKline (GSK) in March 2010 to discover and develop new medicines against targets for rare and serious diseases, including infectious diseases and some conditions causing blindness.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember_lbl" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GlaxoSmithKlineCollaborationMember_lbl1" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember_lbl1">Glaxo Smith Kline Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember_lbl1" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GlaxoSmithKlineCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GlaxoSmithKlineCollaborationMember_lbl2" xml:lang="en-US" id="ions_GlaxoSmithKlineCollaborationMember_lbl2">GSK [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GlaxoSmithKlineCollaborationMember" xlink:to="ions_GlaxoSmithKlineCollaborationMember_lbl2" xlink:title="label: GlaxoSmithKlineCollaborationMember to ions_GlaxoSmithKlineCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NovartisCollaborationMember" xlink:label="NovartisCollaborationMember" xlink:title="NovartisCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NovartisCollaborationMember_lbl" xml:lang="en-US" id="ions_NovartisCollaborationMember_lbl">Collaboration agreement entered into with Novartis International AG (Novartis) in January 2017 to develop and commercialize pelacarsen and olezarsen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember_lbl" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NovartisCollaborationMember_lbl1" xml:lang="en-US" id="ions_NovartisCollaborationMember_lbl1">Novartis Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember_lbl1" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NovartisCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NovartisCollaborationMember_lbl2" xml:lang="en-US" id="ions_NovartisCollaborationMember_lbl2">Novartis [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NovartisCollaborationMember" xlink:to="ions_NovartisCollaborationMember_lbl2" xlink:title="label: NovartisCollaborationMember to ions_NovartisCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl">Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Line Items]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2">Collaborative Arrangements and Licensing Agreements [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:label="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:title="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl">Disclosure of information about collaborative arrangements and non-collaborative arrangement transactions.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1">Collaborative Arrangements and Non-collaborative Arrangement Transactions Disclosure [Table]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable" xlink:to="ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" xlink:title="label: CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable to ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AlnylamPharmaceuticalsIncMember" xlink:label="AlnylamPharmaceuticalsIncMember" xlink:title="AlnylamPharmaceuticalsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AlnylamPharmaceuticalsIncMember_lbl" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember_lbl">Represents activity related to Alnylam Pharmaceuticals, Inc..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember_lbl" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AlnylamPharmaceuticalsIncMember_lbl1" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember_lbl1">Alnylam Pharmaceuticals, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember_lbl1" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AlnylamPharmaceuticalsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AlnylamPharmaceuticalsIncMember_lbl2" xml:lang="en-US" id="ions_AlnylamPharmaceuticalsIncMember_lbl2">Alnylam [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AlnylamPharmaceuticalsIncMember" xlink:to="ions_AlnylamPharmaceuticalsIncMember_lbl2" xlink:title="label: AlnylamPharmaceuticalsIncMember to ions_AlnylamPharmaceuticalsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AccruedInLicensingFeesCurrent" xlink:label="AccruedInLicensingFeesCurrent" xlink:title="AccruedInLicensingFeesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl1">Accrued in-licensing fees, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl1" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedInLicensingFeesCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedInLicensingFeesCurrent_lbl2" xml:lang="en-US" id="ions_AccruedInLicensingFeesCurrent_lbl2">In-licensing expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedInLicensingFeesCurrent" xlink:to="ions_AccruedInLicensingFeesCurrent_lbl2" xlink:title="label: AccruedInLicensingFeesCurrent to ions_AccruedInLicensingFeesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AccruedClinicalExpenses" xlink:label="AccruedClinicalExpenses" xlink:title="AccruedClinicalExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedClinicalExpenses_lbl" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedClinicalExpenses_lbl1" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl1">Accrued clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl1" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedClinicalExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedClinicalExpenses_lbl2" xml:lang="en-US" id="ions_AccruedClinicalExpenses_lbl2">Clinical expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedClinicalExpenses" xlink:to="ions_AccruedClinicalExpenses_lbl2" xlink:title="label: AccruedClinicalExpenses to ions_AccruedClinicalExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AccruedCommercialExpensesCurrent" xlink:label="AccruedCommercialExpensesCurrent" xlink:title="AccruedCommercialExpensesCurrent" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl">Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl1" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl1">Accrued commercial expenses, Current</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl1" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AccruedCommercialExpensesCurrent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AccruedCommercialExpensesCurrent_lbl2" xml:lang="en-US" id="ions_AccruedCommercialExpensesCurrent_lbl2">Commercial expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AccruedCommercialExpensesCurrent" xlink:to="ions_AccruedCommercialExpensesCurrent_lbl2" xlink:title="label: AccruedCommercialExpensesCurrent to ions_AccruedCommercialExpensesCurrent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DebtInstrumentNumberOfConvertibleNotes" xlink:label="DebtInstrumentNumberOfConvertibleNotes" xlink:title="DebtInstrumentNumberOfConvertibleNotes" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl">Number of outstanding convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1">Debt Instrument, Number of convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xml:lang="en-US" id="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2">Number of outstanding convertible notes</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentNumberOfConvertibleNotes" xlink:to="ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" xlink:title="label: DebtInstrumentNumberOfConvertibleNotes to ions_DebtInstrumentNumberOfConvertibleNotes_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AstrazenecaCollaborationEplontersenMember" xlink:label="AstrazenecaCollaborationEplontersenMember" xlink:title="AstrazenecaCollaborationEplontersenMember" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl">Collaboration agreement entered into with AstraZeneca PLC in December 2021 to develop and commercialize eplontersen. Eplontersen, formerly known as IONIS-TTR-L and AKCEA-TTR-L, is a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl1">AstraZeneca Collaboration, Eplontersen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl1" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl2">Eplontersen Collaboration with AstraZeneca [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl2" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_AstrazenecaCollaborationEplontersenMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_AstrazenecaCollaborationEplontersenMember_lbl3" xml:lang="en-US" id="ions_AstrazenecaCollaborationEplontersenMember_lbl3">Eplontersen Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AstrazenecaCollaborationEplontersenMember" xlink:to="ions_AstrazenecaCollaborationEplontersenMember_lbl3" xlink:title="label: AstrazenecaCollaborationEplontersenMember to ions_AstrazenecaCollaborationEplontersenMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:label="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:title="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl">Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1">Incremental Common Shares Attributable to Employee Stock Purchase Plan</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xml:lang="en-US" id="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2">Shares issuable related to our ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan" xlink:to="ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" xlink:title="label: IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan to ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2">After one year but within two years</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl">The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within One Year, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2">One year or less</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl">The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1">Available-for-sale Securities, Debt Maturities, Total, Percentage</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2">Total</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage" xlink:to="ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" xlink:title="label: AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage to ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, within Two Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage_lbl2">Percentage of available-for-sale securities with a maturity of less than two years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:label="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" xlink:title="AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage" />
    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl">The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl1">Available-for-sale Securities, Debt Maturities, after Two Through Three and One Half Years, Percentage</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2" xml:lang="en-US" id="ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage_lbl2">After two years but within three and a half years</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumContractMaturityPeriodRange3" xlink:label="MaximumContractMaturityPeriodRange3" xlink:title="MaximumContractMaturityPeriodRange3" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange3_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange3_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange3_lbl">The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumContractMaturityPeriodRange1" xlink:label="MaximumContractMaturityPeriodRange1" xlink:title="MaximumContractMaturityPeriodRange1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange1_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange1_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange1_lbl">The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumContractMaturityPeriodRange2" xlink:label="MaximumContractMaturityPeriodRange2" xlink:title="MaximumContractMaturityPeriodRange2" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumContractMaturityPeriodRange2_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumContractMaturityPeriodRange2_lbl" xml:lang="en-US" id="ions_MaximumContractMaturityPeriodRange2_lbl">The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumContractMaturityPeriodRange2" xlink:to="ions_MaximumContractMaturityPeriodRange2_lbl2" xlink:title="label: MaximumContractMaturityPeriodRange2 to ions_MaximumContractMaturityPeriodRange2_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:label="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" xlink:title="EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleNotesDisclosureTable" xlink:to="ions_ConvertibleNotesDisclosureTable_lbl1" xlink:title="label: ConvertibleNotesDisclosureTable to ions_ConvertibleNotesDisclosureTable_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LesseeOperatingLeaseInformationTableTextBlock" xlink:label="LesseeOperatingLeaseInformationTableTextBlock" xlink:title="LesseeOperatingLeaseInformationTableTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl">Tabular disclosure of information on lessee's operating leases, including carrying value of right-of-use assets and lease liabilities, weighted-average remaining term and weighted-average discount rate.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1">Lessee, Operating Lease Information [Table Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2">Amounts Related to Operating Leases</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseInformationTableTextBlock" xlink:to="ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" xlink:title="label: LesseeOperatingLeaseInformationTableTextBlock to ions_LesseeOperatingLeaseInformationTableTextBlock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:label="IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:title="IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl">Increase (decrease) in the number of shares in the "fungible" share reserve for each share of common stock returning from a full value award.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1">Increase (decrease) in fungible share reserve for each share returning from full value award</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward" xlink:to="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" xlink:title="label: IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward to ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl2" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward_lbl2">Increase in fungible share reserve for each share returning from a full value award (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:label="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:title="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl">Increase (decrease) in the number of shares in the "fungible" share reserve for each share issued pursuant to full value award.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:to="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" xlink:title="label: IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward to ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1">Increase (decrease) in fungible share reserve for each share issued pursuant to full value award</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:to="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" xlink:title="label: IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward to ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl2" xml:lang="en-US" id="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl2">Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward" xlink:to="ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl2" xlink:title="label: IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward to ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EmployeeStockPurchasePlanMember" xlink:label="EmployeeStockPurchasePlanMember" xlink:title="EmployeeStockPurchasePlanMember" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanMember_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember_lbl">Represents the 2009 Employee Stock Purchase Plan, as amended and restated, which permits full-time employees to purchase common stock through payroll deductions at a percentage of the fair market value.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember_lbl" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanMember_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember_lbl1">Employee Stock Purchase Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember_lbl1" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanMember_lbl2" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanMember_lbl2">Employee Stock Purchase Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanMember" xlink:to="ions_EmployeeStockPurchasePlanMember_lbl2" xlink:title="label: EmployeeStockPurchasePlanMember to ions_EmployeeStockPurchasePlanMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_StockOptionPlan1989Member" xlink:label="StockOptionPlan1989Member" xlink:title="StockOptionPlan1989Member" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_StockOptionPlan1989Member_lbl" xml:lang="en-US" id="ions_StockOptionPlan1989Member_lbl">Represents the 1989 Stock Option Plan, which provides the issuance of non-qualified and incentive stock options for the purchase of common stock to the entity's employees, directors and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionPlan1989Member" xlink:to="ions_StockOptionPlan1989Member_lbl" xlink:title="label: StockOptionPlan1989Member to ions_StockOptionPlan1989Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_StockOptionPlan1989Member_lbl1" xml:lang="en-US" id="ions_StockOptionPlan1989Member_lbl1">Stock Option Plan 1989 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionPlan1989Member" xlink:to="ions_StockOptionPlan1989Member_lbl1" xlink:title="label: StockOptionPlan1989Member to ions_StockOptionPlan1989Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_StockOptionPlan1989Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_StockOptionPlan1989Member_lbl2" xml:lang="en-US" id="ions_StockOptionPlan1989Member_lbl2">1989 Stock Option Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="StockOptionPlan1989Member" xlink:to="ions_StockOptionPlan1989Member_lbl2" xlink:title="label: StockOptionPlan1989Member to ions_StockOptionPlan1989Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NonemployeeDirectorsStockOptionPlan2002Member" xlink:label="NonemployeeDirectorsStockOptionPlan2002Member" xlink:title="NonemployeeDirectorsStockOptionPlan2002Member" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl">Represents the 2002 Non-Employee Directors Stock Option Plan, which provided for the issuance of stock options to the entity's non-employee directors for the purchase of common stock.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1">Nonemployee Directors' Stock Option Plan 2002 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl2" xml:lang="en-US" id="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl2">2002 Non-Employee Directors' Stock Option Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NonemployeeDirectorsStockOptionPlan2002Member" xlink:to="ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl2" xlink:title="label: NonemployeeDirectorsStockOptionPlan2002Member to ions_NonemployeeDirectorsStockOptionPlan2002Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:label="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:title="EmployeeStockPurchasePlanSharesAvailableForPurchase" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl">The number of shares available for purchase under an employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1">Employee Stock Purchase Plan, Shares Available for Purchase</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl2" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl2">Shares available for purchase under ESPP (in shares)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanSharesAvailableForPurchase" xlink:to="ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl2" xlink:title="label: EmployeeStockPurchasePlanSharesAvailableForPurchase to ions_EmployeeStockPurchasePlanSharesAvailableForPurchase_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:label="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:title="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl">Weighted average sales price of shares purchased through an employee stock purchase plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1">Employee Stock Purchase Plan, Weighted Average Sales Price of Shares Purchased</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl2" xml:lang="en-US" id="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl2">Weighted average purchase price (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased" xlink:to="ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl2" xlink:title="label: EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased to ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl">Represents the holding period from the date of purchase for stock purchased under the plan.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Holding Period</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl2">Holding period for purchased stock</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">Period of time after a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Period after change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xml:lang="en-US" id="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2">Period after change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:title="label: PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">Period of time before a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xml:lang="en-US" id="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2">Period before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:title="label: PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:label="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:title="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl">The number of executive officers terminated by the Company during the period that begins three months before and ends twelve months following a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xml:lang="en-US" id="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2">Number of executive officers terminated before change in control when vesting will accelerate for executive officers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers" xlink:to="ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" xlink:title="label: NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers to ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ResearchDevelopmentAndPatentMember" xlink:label="ResearchDevelopmentAndPatentMember" xlink:title="ResearchDevelopmentAndPatentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl">Primary financial statement caption encompassing research, development and patent expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl1">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl1" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentMember_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentMember_lbl2">Research, Development and Patent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentMember" xlink:to="ions_ResearchDevelopmentAndPatentMember_lbl2" xlink:title="label: ResearchDevelopmentAndPatentMember to ions_ResearchDevelopmentAndPatentMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" xlink:label="LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" xlink:title="LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl" xml:lang="en-US" id="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl">Disclosure of accounting policy for estimating the liability for clinical development costs.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" xlink:to="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl" xlink:title="label: LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock to ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl1" xml:lang="en-US" id="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl1">Liability for Clinical Development Costs, Policy [Policy Text Block]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" xlink:to="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl1" xlink:title="label: LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock to ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl2" xml:lang="en-US" id="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl2">Estimated Liability for Clinical Development Costs</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock" xlink:to="ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl2" xlink:title="label: LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock to ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CommercialRawMaterialsMember" xlink:label="CommercialRawMaterialsMember" xlink:title="CommercialRawMaterialsMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CommercialRawMaterialsMember_lbl" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl">Raw materials purchased for manufacturing medicines for commercial production.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialRawMaterialsMember_lbl1" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl1">Commercial Raw Materials [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl1" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialRawMaterialsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialRawMaterialsMember_lbl2" xml:lang="en-US" id="ions_CommercialRawMaterialsMember_lbl2">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialRawMaterialsMember" xlink:to="ions_CommercialRawMaterialsMember_lbl2" xlink:title="label: CommercialRawMaterialsMember to ions_CommercialRawMaterialsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ClinicalRawMaterialsMember" xlink:label="ClinicalRawMaterialsMember" xlink:title="ClinicalRawMaterialsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ClinicalRawMaterialsMember_lbl" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl">Raw materials purchased for use in producing medicines that have alternative future uses until they are used.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ClinicalRawMaterialsMember_lbl1" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl1">Clinical Raw Materials [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl1" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ClinicalRawMaterialsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ClinicalRawMaterialsMember_lbl2" xml:lang="en-US" id="ions_ClinicalRawMaterialsMember_lbl2">Clinical [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ClinicalRawMaterialsMember" xlink:to="ions_ClinicalRawMaterialsMember_lbl2" xlink:title="label: ClinicalRawMaterialsMember to ions_ClinicalRawMaterialsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MetagenomiCollaborationMember" xlink:label="MetagenomiCollaborationMember" xlink:title="MetagenomiCollaborationMember" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiCollaborationMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MetagenomiCollaborationMember_lbl" xml:lang="en-US" id="ions_MetagenomiCollaborationMember_lbl">Collaboration agreement entered into with Metagenomi in November 2022 to research, develop and commercialize investigational medicines for up to eight potential targets using gene editing technologies.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MetagenomiCollaborationMember" xlink:to="ions_MetagenomiCollaborationMember_lbl" xlink:title="label: MetagenomiCollaborationMember to ions_MetagenomiCollaborationMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiCollaborationMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MetagenomiCollaborationMember_lbl1" xml:lang="en-US" id="ions_MetagenomiCollaborationMember_lbl1">Metagenomi Collaboration [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MetagenomiCollaborationMember" xlink:to="ions_MetagenomiCollaborationMember_lbl1" xlink:title="label: MetagenomiCollaborationMember to ions_MetagenomiCollaborationMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MetagenomiCollaborationMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MetagenomiCollaborationMember_lbl2" xml:lang="en-US" id="ions_MetagenomiCollaborationMember_lbl2">Metagenomi License Agreement [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MetagenomiCollaborationMember" xlink:to="ions_MetagenomiCollaborationMember_lbl2" xlink:title="label: MetagenomiCollaborationMember to ions_MetagenomiCollaborationMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PaymentToLicenseIntellectualProperty" xlink:label="PaymentToLicenseIntellectualProperty" xlink:title="PaymentToLicenseIntellectualProperty" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToLicenseIntellectualProperty_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PaymentToLicenseIntellectualProperty_lbl" xml:lang="en-US" id="ions_PaymentToLicenseIntellectualProperty_lbl">Amount of cash outflow to license intellectual property under a collaboration and license agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseIntellectualProperty" xlink:to="ions_PaymentToLicenseIntellectualProperty_lbl" xlink:title="label: PaymentToLicenseIntellectualProperty to ions_PaymentToLicenseIntellectualProperty_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToLicenseIntellectualProperty_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PaymentToLicenseIntellectualProperty_lbl1" xml:lang="en-US" id="ions_PaymentToLicenseIntellectualProperty_lbl1">Payment to license intellectual property</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseIntellectualProperty" xlink:to="ions_PaymentToLicenseIntellectualProperty_lbl1" xlink:title="label: PaymentToLicenseIntellectualProperty to ions_PaymentToLicenseIntellectualProperty_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PaymentToLicenseIntellectualProperty_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PaymentToLicenseIntellectualProperty_lbl2" xml:lang="en-US" id="ions_PaymentToLicenseIntellectualProperty_lbl2">Payment to license intellectual property</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PaymentToLicenseIntellectualProperty" xlink:to="ions_PaymentToLicenseIntellectualProperty_lbl2" xlink:title="label: PaymentToLicenseIntellectualProperty to ions_PaymentToLicenseIntellectualProperty_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CollaborativeArrangementAndLicensingAgreementAbstract" xlink:label="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:title="CollaborativeArrangementAndLicensingAgreementAbstract" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xml:lang="en-US" id="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1">Collaborative Arrangement and Licensing Agreement [Abstract]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeArrangementAndLicensingAgreementAbstract" xlink:to="ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" xlink:title="label: CollaborativeArrangementAndLicensingAgreementAbstract to ions_CollaborativeArrangementAndLicensingAgreementAbstract_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized" xlink:label="NumberOfTargetsToBeResearchedDevelopedAndCommercialized" xlink:title="NumberOfTargetsToBeResearchedDevelopedAndCommercialized" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl" xml:lang="en-US" id="ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized_lbl">The number of targets to be researched, developed and commercialized under the collaboration agreement.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:label="WeightedAverageNumberOfSharesOwnedInSubsidiary" xlink:title="WeightedAverageNumberOfSharesOwnedInSubsidiary" />
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IonisCoreMember" xlink:label="IonisCoreMember" xlink:title="IonisCoreMember" />
    <link:label xlink:type="resource" xlink:label="ions_IonisCoreMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IonisCoreMember_lbl" xml:lang="en-US" id="ions_IonisCoreMember_lbl">Reportable segment in which the Company is exploiting a novel drug discovery platform created to generate a broad pipeline of first-in-class or best-in-class drugs for the Company and its partners. This segment generates revenue from a multifaceted partnering strategy. This strategy includes revenue from collaborations with preferred partners, traditional alliances and working with a consortium of companies that can exploit the Company's drugs and technology. Revenue from collaborations with preferred partners and traditional alliances may consist of upfront payments, milestone payments, licensing fees and royalties.</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_RoyaltyMonetizationIssuanceCosts" xlink:label="RoyaltyMonetizationIssuanceCosts" xlink:title="RoyaltyMonetizationIssuanceCosts" />
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NonCashCapitalAndPatentExpenditures" xlink:label="NonCashCapitalAndPatentExpenditures" xlink:title="NonCashCapitalAndPatentExpenditures" />
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EarlyRepaymentOfConvertibleDebt" xlink:label="EarlyRepaymentOfConvertibleDebt" xlink:title="EarlyRepaymentOfConvertibleDebt" />
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:label="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" xlink:title="OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary" />
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl">The weighted average grant-date fair value of options exercised during the reporting period as calculated by applying the disclosed option pricing methodology.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Options, Exercises in Period, Weighted Average Fair Value</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl2">Weighted-average fair value of options exercised (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EquityIncentivePlan2020Member" xlink:label="EquityIncentivePlan2020Member" xlink:title="EquityIncentivePlan2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2020Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member_lbl">In December 2020, the Company amended and restated the Akcea 2015 Equity Incentive Plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to 2.6 million shares of Common Stock to employees, directors and consultants who were employees of Akcea prior to the Akcea Acquisition.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member_lbl" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2020Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member_lbl1">Equity Incentive Plan 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member_lbl1" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2020Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2020Member_lbl2" xml:lang="en-US" id="ions_EquityIncentivePlan2020Member_lbl2">2020 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2020Member" xlink:to="ions_EquityIncentivePlan2020Member_lbl2" xlink:title="label: EquityIncentivePlan2020Member to ions_EquityIncentivePlan2020Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EquityIncentivePlan2011Member" xlink:label="EquityIncentivePlan2011Member" xlink:title="EquityIncentivePlan2011Member" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquityIncentivePlan2011Member_lbl" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl">Represents the stock option plan that provides for the issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to employees, directors, and consultants.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquityIncentivePlan2011Member_lbl1" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl1">Equity Incentive Plan 2011 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl1" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquityIncentivePlan2011Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquityIncentivePlan2011Member_lbl2" xml:lang="en-US" id="ions_EquityIncentivePlan2011Member_lbl2">2011 Equity Incentive Plan [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquityIncentivePlan2011Member" xlink:to="ions_EquityIncentivePlan2011Member_lbl2" xlink:title="label: EquityIncentivePlan2011Member to ions_EquityIncentivePlan2011Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_IssuedAfterDecember312021Member" xlink:label="IssuedAfterDecember312021Member" xlink:title="IssuedAfterDecember312021Member" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_IssuedAfterDecember312021Member_lbl" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member_lbl">Awards issued after December 31, 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member_lbl" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_IssuedAfterDecember312021Member_lbl1" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member_lbl1">Issued after December 31, 2021 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member_lbl1" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_IssuedAfterDecember312021Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_IssuedAfterDecember312021Member_lbl2" xml:lang="en-US" id="ions_IssuedAfterDecember312021Member_lbl2">Issued after December 31, 2021 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="IssuedAfterDecember312021Member" xlink:to="ions_IssuedAfterDecember312021Member_lbl2" xlink:title="label: IssuedAfterDecember312021Member to ions_IssuedAfterDecember312021Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BoardOfDirectorStockOptionMember" xlink:label="BoardOfDirectorStockOptionMember" xlink:title="BoardOfDirectorStockOptionMember" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl">An arrangement whereby a member of the Board of Directors is entitled to receive in the future, subject to vesting and other restrictions, a number of shares in the entity at a specified price, as defined in the agreement, as a form of compensation.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl1" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl1">Board of Director Stock Option [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl1" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BoardOfDirectorStockOptionMember_lbl2" xml:lang="en-US" id="ions_BoardOfDirectorStockOptionMember_lbl2">Board of Director Stock Options [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BoardOfDirectorStockOptionMember" xlink:to="ions_BoardOfDirectorStockOptionMember_lbl2" xlink:title="label: BoardOfDirectorStockOptionMember to ions_BoardOfDirectorStockOptionMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:label="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:title="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl">Number of purchase and sale agreements entered into with a real estate investor.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xml:lang="en-US" id="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2">Number of purchase and sale agreements entered into with real estate investor</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor" xlink:to="ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" xlink:title="label: NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor to ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PrimaryResearchAndDevelopmentFacilityMember" xlink:label="PrimaryResearchAndDevelopmentFacilityMember" xlink:title="PrimaryResearchAndDevelopmentFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl">Facility constructed for the entity's primary research and development activities under a lease agreement with an affiliate of BioMed Realty, L.P.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1">Primary Research and Development Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2">Primary R&amp;D Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMember to ions_PrimaryResearchAndDevelopmentFacilityMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LongTermMortgageDebtMember" xlink:label="LongTermMortgageDebtMember" xlink:title="LongTermMortgageDebtMember" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermMortgageDebtMember_lbl" xml:lang="en-US" id="ions_LongTermMortgageDebtMember_lbl">Two loan agreements with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's research and development and manufacturing facilities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember_lbl" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LongTermMortgageDebtMember_lbl1" xml:lang="en-US" id="ions_LongTermMortgageDebtMember_lbl1">Long-term Mortgage Debt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember_lbl1" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermMortgageDebtMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LongTermMortgageDebtMember_lbl2" xml:lang="en-US" id="ions_LongTermMortgageDebtMember_lbl2">Long-term Mortgage Debt [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LongTermMortgageDebtMember" xlink:to="ions_LongTermMortgageDebtMember_lbl2" xlink:title="label: LongTermMortgageDebtMember to ions_LongTermMortgageDebtMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:label="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:title="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl">The number of purchased facilities financed with mortgage debt.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1">Number of purchased facilities financed with mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl2" xml:lang="en-US" id="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl2">Number of purchased facilities financed with mortgage debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfPurchasedFacilitiesFinancedWithMortgageDebt" xlink:to="ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl2" xlink:title="label: NumberOfPurchasedFacilitiesFinancedWithMortgageDebt to ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:label="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:title="PrimaryResearchAndDevelopmentFacilityMortgageMember" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl">Loan agreement with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's primary research and development (R&amp;D) facility.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1">Primary Research and Development Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl2" xml:lang="en-US" id="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl2">Primary R&amp;D Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PrimaryResearchAndDevelopmentFacilityMortgageMember" xlink:to="ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl2" xlink:title="label: PrimaryResearchAndDevelopmentFacilityMortgageMember to ions_PrimaryResearchAndDevelopmentFacilityMortgageMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ManufacturingFacilityMortgageMember" xlink:label="ManufacturingFacilityMortgageMember" xlink:title="ManufacturingFacilityMortgageMember" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ManufacturingFacilityMortgageMember_lbl" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember_lbl">Loan agreement with UBS AG entered into on July 18, 2017 to finance the purchase of the Company's research and development facility.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ManufacturingFacilityMortgageMember_lbl1" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember_lbl1">Manufacturing Facility Mortgage [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ManufacturingFacilityMortgageMember" xlink:to="ions_ManufacturingFacilityMortgageMember_lbl1" xlink:title="label: ManufacturingFacilityMortgageMember to ions_ManufacturingFacilityMortgageMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ManufacturingFacilityMortgageMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ManufacturingFacilityMortgageMember_lbl2" xml:lang="en-US" id="ions_ManufacturingFacilityMortgageMember_lbl2">Manufacturing Facility Mortgage [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:label="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:title="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl">Period of time to make only payments of interest on the mortgage loan, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1" xml:lang="en-US" id="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl1">Period to make interest only payments on mortgage loan</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodToMakeInterestOnlyPaymentsOnMortgageLoan" xlink:to="ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" xlink:title="label: PeriodToMakeInterestOnlyPaymentsOnMortgageLoan to ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NetProceedsFromSaleOfBuildingsAndLand" xlink:label="NetProceedsFromSaleOfBuildingsAndLand" xlink:title="NetProceedsFromSaleOfBuildingsAndLand" />
    <link:label xlink:type="resource" xlink:label="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl" xml:lang="en-US" id="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl">The cash inflow from sale of buildings and held for use in connection with a sale and leaseback transaction, net of the cash outflow to repay the outstanding mortgage debt and pay property taxes and fees.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetProceedsFromSaleOfBuildingsAndLand" xlink:to="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl1" xlink:title="label: NetProceedsFromSaleOfBuildingsAndLand to ions_NetProceedsFromSaleOfBuildingsAndLand_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl2" xml:lang="en-US" id="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl2">Net proceeds from sale of real estate assets</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NetProceedsFromSaleOfBuildingsAndLand" xlink:to="ions_NetProceedsFromSaleOfBuildingsAndLand_lbl2" xlink:title="label: NetProceedsFromSaleOfBuildingsAndLand to ions_NetProceedsFromSaleOfBuildingsAndLand_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EquipmentAndComputerSoftwareMember" xlink:label="EquipmentAndComputerSoftwareMember" xlink:title="EquipmentAndComputerSoftwareMember" />
    <link:label xlink:type="resource" xlink:label="ions_EquipmentAndComputerSoftwareMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EquipmentAndComputerSoftwareMember_lbl" xml:lang="en-US" id="ions_EquipmentAndComputerSoftwareMember_lbl">Long lived, depreciable assets that are used in the creation, maintenance and utilization of information systems and purchased software applications and internally developed software for long-term internal use. Includes other tangible personal property, nonconsumable in nature, with finite lives used to produce goods and services, such as laboratory, manufacturing and other equipment.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquipmentAndComputerSoftwareMember" xlink:to="ions_EquipmentAndComputerSoftwareMember_lbl" xlink:title="label: EquipmentAndComputerSoftwareMember to ions_EquipmentAndComputerSoftwareMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EquipmentAndComputerSoftwareMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EquipmentAndComputerSoftwareMember_lbl1" xml:lang="en-US" id="ions_EquipmentAndComputerSoftwareMember_lbl1">Equipment and Computer Software [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquipmentAndComputerSoftwareMember" xlink:to="ions_EquipmentAndComputerSoftwareMember_lbl1" xlink:title="label: EquipmentAndComputerSoftwareMember to ions_EquipmentAndComputerSoftwareMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EquipmentAndComputerSoftwareMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EquipmentAndComputerSoftwareMember_lbl2" xml:lang="en-US" id="ions_EquipmentAndComputerSoftwareMember_lbl2">Computer Software, Laboratory, Manufacturing and Other Equipment [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EquipmentAndComputerSoftwareMember" xlink:to="ions_EquipmentAndComputerSoftwareMember_lbl2" xlink:title="label: EquipmentAndComputerSoftwareMember to ions_EquipmentAndComputerSoftwareMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PropertyPlantAndEquipmentExcludingLandMember" xlink:label="PropertyPlantAndEquipmentExcludingLandMember" xlink:title="PropertyPlantAndEquipmentExcludingLandMember" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl">Physical assets used in the normal conduct of business and not intended for resale, excluding land. Examples include, but are not limited to, buildings, land and leasehold improvements, machinery and equipment, office equipment, and furniture and fixtures.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xml:lang="en-US" id="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1">Property, Plant and Equipment, Excluding Land [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PropertyPlantAndEquipmentExcludingLandMember" xlink:to="ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" xlink:title="label: PropertyPlantAndEquipmentExcludingLandMember to ions_PropertyPlantAndEquipmentExcludingLandMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:label="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:title="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted prior to January 1, 2022.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1">Share-based Payment Arrangement, Options Granted Prior to January 1, 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2">Stock Options Granted Prior to January 1, 2022 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member to ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:label="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:title="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl">Share-based payment arrangement granting right, subject to vesting and other restrictions, to purchase or sell certain number of shares at predetermined price for specified period of time granted on January 1, 2022 and thereafter.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1">Share-based Payment Arrangement, Options Granted on January 1, 2022 and Thereafter [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2">Stock Options Granted on January 1, 2022 and Thereafter [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember" xlink:to="ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" xlink:title="label: ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember to ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl">Percentage of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Percentage of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2">Percentage of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl">Number of units guaranteed to vest under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of units guaranteed to vest</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest_lbl2">Number of units guaranteed to vest (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:label="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:title="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl">Number of separate performance periods under share-based payment arrangement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1">Share-based Compensation Arrangement by Share-based Payment Award, Number of Performance Periods</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods" xlink:to="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" xlink:title="label: ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods to ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2" xml:lang="en-US" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods_lbl2">Number of performance periods</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_GrantedAfterJune2020Member" xlink:label="GrantedAfterJune2020Member" xlink:title="GrantedAfterJune2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAfterJune2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedAfterJune2020Member_lbl" xml:lang="en-US" id="ions_GrantedAfterJune2020Member_lbl">Awards granted after June 2020.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAfterJune2020Member" xlink:to="ions_GrantedAfterJune2020Member_lbl" xlink:title="label: GrantedAfterJune2020Member to ions_GrantedAfterJune2020Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAfterJune2020Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedAfterJune2020Member_lbl1" xml:lang="en-US" id="ions_GrantedAfterJune2020Member_lbl1">Granted After June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAfterJune2020Member" xlink:to="ions_GrantedAfterJune2020Member_lbl1" xlink:title="label: GrantedAfterJune2020Member to ions_GrantedAfterJune2020Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedAfterJune2020Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedAfterJune2020Member_lbl2" xml:lang="en-US" id="ions_GrantedAfterJune2020Member_lbl2">Granted After June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedAfterJune2020Member" xlink:to="ions_GrantedAfterJune2020Member_lbl2" xlink:title="label: GrantedAfterJune2020Member to ions_GrantedAfterJune2020Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_GrantedPriorToJune2020Member" xlink:label="GrantedPriorToJune2020Member" xlink:title="GrantedPriorToJune2020Member" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_GrantedPriorToJune2020Member_lbl" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member_lbl">Awards granted prior to June 2020.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member_lbl" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_GrantedPriorToJune2020Member_lbl1" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member_lbl1">Granted Prior to June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member_lbl1" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_GrantedPriorToJune2020Member_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_GrantedPriorToJune2020Member_lbl2" xml:lang="en-US" id="ions_GrantedPriorToJune2020Member_lbl2">Granted Prior to June 2020 [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="GrantedPriorToJune2020Member" xlink:to="ions_GrantedPriorToJune2020Member_lbl2" xlink:title="label: GrantedPriorToJune2020Member to ions_GrantedPriorToJune2020Member_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:label="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:title="ShareBasedPaymentArrangementBoardOfDirectorMember" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl">Recipient, of award granted under share-based payment arrangement, over whom grantor exercises or has right to exercise sufficient control to establish employer-employee relationship based on law of pertinent jurisdiction. Includes nonemployee director treated as employee when acting as member of board of directors, if elected by grantor's shareholders or appointed to board position to be filled by shareholder election when existing term expires.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1">Share-based Payment Arrangement, Board of Director [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xml:lang="en-US" id="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2">Board of Directors [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ShareBasedPaymentArrangementBoardOfDirectorMember" xlink:to="ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" xlink:title="label: ShareBasedPaymentArrangementBoardOfDirectorMember to ions_ShareBasedPaymentArrangementBoardOfDirectorMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PelacarsenMember" xlink:label="PelacarsenMember" xlink:title="PelacarsenMember" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PelacarsenMember_lbl" xml:lang="en-US" id="ions_PelacarsenMember_lbl">Pelacarsen, also known as IONIS-APO(a)-L, AKCEA-APO(a)-L, and TQJ230, is an investigational antisense medicine designed to reduce apolipoprotein(a) in the liver in patients suffering from high levels of the lipoprotein Lp(a).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PelacarsenMember_lbl1" xml:lang="en-US" id="ions_PelacarsenMember_lbl1">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl1" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PelacarsenMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PelacarsenMember_lbl2" xml:lang="en-US" id="ions_PelacarsenMember_lbl2">Pelacarsen [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PelacarsenMember" xlink:to="ions_PelacarsenMember_lbl2" xlink:title="label: PelacarsenMember to ions_PelacarsenMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_UpfrontRoyaltyPaymentReceived" xlink:label="UpfrontRoyaltyPaymentReceived" xlink:title="UpfrontRoyaltyPaymentReceived" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl">The amount of upfront payments received during the period under the royalty purchase agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl1" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl1">Upfront royalty payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl1" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_UpfrontRoyaltyPaymentReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_UpfrontRoyaltyPaymentReceived_lbl2" xml:lang="en-US" id="ions_UpfrontRoyaltyPaymentReceived_lbl2">Upfront payment received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="UpfrontRoyaltyPaymentReceived" xlink:to="ions_UpfrontRoyaltyPaymentReceived_lbl2" xlink:title="label: UpfrontRoyaltyPaymentReceived to ions_UpfrontRoyaltyPaymentReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:label="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:title="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl">Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl2" xml:lang="en-US" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl2">Maximum royalty payments made before royalty interest reverts back</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" xlink:to="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl2" xlink:title="label: MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack to ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:label="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:title="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" />
    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl">The maximum amount of payments receivable for additional milestones under the royalty purchase agreement.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xml:lang="en-US" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1">Maximum amount of payments receivable for additional milestones</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" xlink:to="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" xlink:title="label: MaximumAmountOfPaymentsReceivableForAdditionalMilestones to ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:label="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:title="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl">The percentage of royalty payments paid on annual sales of medicine.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl3" xml:lang="en-US" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl3">Percentage of royalty payments paid on annual sales of medicine</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" xlink:to="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl3" xlink:title="label: PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine to ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_SpinrazaMember" xlink:label="SpinrazaMember" xlink:title="SpinrazaMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaMember_lbl" xml:lang="en-US" id="ions_SpinrazaMember_lbl">Nusinersen, marketed as Spinraza, is a medicine used in treating spinal muscular atrophy (SMA), a progressive, debilitating and often fatal genetic disease.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_SpinrazaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaMember_lbl1" xml:lang="en-US" id="ions_SpinrazaMember_lbl1">Spinraza [Member]</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DeferredTaxAssetsLeasingArrangements" xlink:label="DeferredTaxAssetsLeasingArrangements" xlink:title="DeferredTaxAssetsLeasingArrangements" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLeasingArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsLeasingArrangements_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsLeasingArrangements_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to leasing arrangements.</link:label>
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLeasingArrangements" xlink:to="ions_DeferredTaxAssetsLeasingArrangements_lbl1" xlink:title="label: DeferredTaxAssetsLeasingArrangements to ions_DeferredTaxAssetsLeasingArrangements_lbl1" />
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    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLeasingArrangements" xlink:to="ions_DeferredTaxAssetsLeasingArrangements_lbl2" xlink:title="label: DeferredTaxAssetsLeasingArrangements to ions_DeferredTaxAssetsLeasingArrangements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:label="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:title="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl">Represents the net amount of deferred tax assets (before reduction for valuation allowance) and liabilities as of the balance sheet date, which result from applying the applicable enacted tax rate to net temporary differences and carryforwards pertaining to assets or liabilities.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:to="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" xlink:title="label: DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance to ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1">Deferred Tax Assets (Liabilities), Net, before Valuation Allowance</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:to="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" xlink:title="label: DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance to ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl2" xlink:role="http://www.xbrl.org/2003/role/totalLabel" xlink:title="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl2" xml:lang="en-US" id="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl2">Net deferred tax asset</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance" xlink:to="ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl2" xlink:title="label: DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance to ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DeferredTaxAssetsFinancingArrangements" xlink:label="DeferredTaxAssetsFinancingArrangements" xlink:title="DeferredTaxAssetsFinancingArrangements" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsFinancingArrangements_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from financing arrangements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsFinancingArrangements" xlink:to="ions_DeferredTaxAssetsFinancingArrangements_lbl" xlink:title="label: DeferredTaxAssetsFinancingArrangements to ions_DeferredTaxAssetsFinancingArrangements_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements_lbl1">Deferred Tax Assets, Financing Arrangements</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsFinancingArrangements" xlink:to="ions_DeferredTaxAssetsFinancingArrangements_lbl1" xlink:title="label: DeferredTaxAssetsFinancingArrangements to ions_DeferredTaxAssetsFinancingArrangements_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsFinancingArrangements_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsFinancingArrangements_lbl2" xml:lang="en-US" id="ions_DeferredTaxAssetsFinancingArrangements_lbl2">Convertible debt</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsFinancingArrangements" xlink:to="ions_DeferredTaxAssetsFinancingArrangements_lbl2" xlink:title="label: DeferredTaxAssetsFinancingArrangements to ions_DeferredTaxAssetsFinancingArrangements_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DeferredTaxAssetsInterestExpenseLimitation" xlink:label="DeferredTaxAssetsInterestExpenseLimitation" xlink:title="DeferredTaxAssetsInterestExpenseLimitation" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from a limitation on interest expense.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsInterestExpenseLimitation" xlink:to="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl" xlink:title="label: DeferredTaxAssetsInterestExpenseLimitation to ions_DeferredTaxAssetsInterestExpenseLimitation_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl1">Deferred Tax Assets, Interest Expense Limitation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsInterestExpenseLimitation" xlink:to="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl1" xlink:title="label: DeferredTaxAssetsInterestExpenseLimitation to ions_DeferredTaxAssetsInterestExpenseLimitation_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl2" xml:lang="en-US" id="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl2">Interest expense limitation</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsInterestExpenseLimitation" xlink:to="ions_DeferredTaxAssetsInterestExpenseLimitation_lbl2" xlink:title="label: DeferredTaxAssetsInterestExpenseLimitation to ions_DeferredTaxAssetsInterestExpenseLimitation_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:label="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:title="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" xml:lang="en-US" id="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl">Amount before allocation of valuation allowances of deferred tax asset attributable to capitalized research and development expenses.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:to="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" xlink:title="label: DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses to ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl1" xml:lang="en-US" id="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl1">Deferred Tax Assets, Capitalized Research and Development Expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:to="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl1" xlink:title="label: DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses to ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl2" xml:lang="en-US" id="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl2">Capitalized research and development expenses</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses" xlink:to="ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl2" xlink:title="label: DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses to ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_TwoSignificantCustomersMember" xlink:label="TwoSignificantCustomersMember" xlink:title="TwoSignificantCustomersMember" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_TwoSignificantCustomersMember_lbl" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl">Two significant corporate partners and leading global pharmaceutical companies that are working alongside the Company to develop the Company's drugs, advance the Company's technology, and prepare to commercialize and sell the Company's drugs under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_TwoSignificantCustomersMember_lbl1" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl1">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl1" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_TwoSignificantCustomersMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_TwoSignificantCustomersMember_lbl2" xml:lang="en-US" id="ions_TwoSignificantCustomersMember_lbl2">Two Significant Customers [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="TwoSignificantCustomersMember" xlink:to="ions_TwoSignificantCustomersMember_lbl2" xlink:title="label: TwoSignificantCustomersMember to ions_TwoSignificantCustomersMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfSignificantCustomers" xlink:label="NumberOfSignificantCustomers" xlink:title="NumberOfSignificantCustomers" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfSignificantCustomers_lbl" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl">The number of significant customers with which the Company does business.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfSignificantCustomers_lbl1" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl1">Number of Significant Customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl1" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfSignificantCustomers_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfSignificantCustomers_lbl2" xml:lang="en-US" id="ions_NumberOfSignificantCustomers_lbl2">Number of significant customers</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfSignificantCustomers" xlink:to="ions_NumberOfSignificantCustomers_lbl2" xlink:title="label: NumberOfSignificantCustomers to ions_NumberOfSignificantCustomers_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_PeriodAfterBillingWhenPaymentIsReceived" xlink:label="PeriodAfterBillingWhenPaymentIsReceived" xlink:title="PeriodAfterBillingWhenPaymentIsReceived" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl">The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1">Period after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xml:lang="en-US" id="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2">Period of time after billing when payment is received</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="PeriodAfterBillingWhenPaymentIsReceived" xlink:to="ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" xlink:title="label: PeriodAfterBillingWhenPaymentIsReceived to ions_PeriodAfterBillingWhenPaymentIsReceived_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_OneSignificantCustomerMember" xlink:label="OneSignificantCustomerMember" xlink:title="OneSignificantCustomerMember" />
    <link:label xlink:type="resource" xlink:label="ions_OneSignificantCustomerMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_OneSignificantCustomerMember_lbl" xml:lang="en-US" id="ions_OneSignificantCustomerMember_lbl">One significant corporate partner and leading global pharmaceutical company that is working alongside the Company to develop the Company's medicines, advance the Company's technology, and prepare to commercialize and sell the Company's medicines under collaborative arrangement and licensing agreements.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OneSignificantCustomerMember" xlink:to="ions_OneSignificantCustomerMember_lbl" xlink:title="label: OneSignificantCustomerMember to ions_OneSignificantCustomerMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_OneSignificantCustomerMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_OneSignificantCustomerMember_lbl1" xml:lang="en-US" id="ions_OneSignificantCustomerMember_lbl1">One Significant Customer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OneSignificantCustomerMember" xlink:to="ions_OneSignificantCustomerMember_lbl1" xlink:title="label: OneSignificantCustomerMember to ions_OneSignificantCustomerMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_OneSignificantCustomerMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_OneSignificantCustomerMember_lbl2" xml:lang="en-US" id="ions_OneSignificantCustomerMember_lbl2">One Significant Customer [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="OneSignificantCustomerMember" xlink:to="ions_OneSignificantCustomerMember_lbl2" xlink:title="label: OneSignificantCustomerMember to ions_OneSignificantCustomerMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CollaborativeAgreementRevenueMember" xlink:label="CollaborativeAgreementRevenueMember" xlink:title="CollaborativeAgreementRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl">Revenue from research and development services performed under a collaborative agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl1" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl1">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl1" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CollaborativeAgreementRevenueMember_lbl2" xml:lang="en-US" id="ions_CollaborativeAgreementRevenueMember_lbl2">Collaborative Agreement Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CollaborativeAgreementRevenueMember" xlink:to="ions_CollaborativeAgreementRevenueMember_lbl2" xlink:title="label: CollaborativeAgreementRevenueMember to ions_CollaborativeAgreementRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ResearchAndDevelopmentRevenueMember" xlink:label="ResearchAndDevelopmentRevenueMember" xlink:title="ResearchAndDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl">Revenue from research and development services.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl1">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl1" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl2">Research and Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl2" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchAndDevelopmentRevenueMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchAndDevelopmentRevenueMember_lbl3" xml:lang="en-US" id="ions_ResearchAndDevelopmentRevenueMember_lbl3">R&amp;D Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchAndDevelopmentRevenueMember" xlink:to="ions_ResearchAndDevelopmentRevenueMember_lbl3" xlink:title="label: ResearchAndDevelopmentRevenueMember to ions_ResearchAndDevelopmentRevenueMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LicensingAndOtherRoyaltiesMember" xlink:label="LicensingAndOtherRoyaltiesMember" xlink:title="LicensingAndOtherRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl">Revenue from license fees and other royalties, excluding royalties from the sale of SPINRAZA.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl1">Licensing and Other Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl1" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_LicensingAndOtherRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_LicensingAndOtherRoyaltiesMember_lbl2">Licensing and Other Royalty Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LicensingAndOtherRoyaltiesMember" xlink:to="ions_LicensingAndOtherRoyaltiesMember_lbl2" xlink:title="label: LicensingAndOtherRoyaltiesMember to ions_LicensingAndOtherRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_SpinrazaRoyaltiesMember" xlink:label="SpinrazaRoyaltiesMember" xlink:title="SpinrazaRoyaltiesMember" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SpinrazaRoyaltiesMember_lbl" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl">Royalty revenues from the sale of SPINRAZA (nusinersen).</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SpinrazaRoyaltiesMember_lbl1" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl1">Spinraza Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl1" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_SpinrazaRoyaltiesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_SpinrazaRoyaltiesMember_lbl2" xml:lang="en-US" id="ions_SpinrazaRoyaltiesMember_lbl2">SPINRAZA Royalties [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SpinrazaRoyaltiesMember" xlink:to="ions_SpinrazaRoyaltiesMember_lbl2" xlink:title="label: SpinrazaRoyaltiesMember to ions_SpinrazaRoyaltiesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CommercialMember" xlink:label="CommercialMember" xlink:title="CommercialMember" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CommercialMember_lbl" xml:lang="en-US" id="ions_CommercialMember_lbl">Revenue from the sale of medicines commercially as well as licensing and royalty revenues from other medicines, including SPINRAZA..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl" xlink:title="label: CommercialMember to ions_CommercialMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CommercialMember_lbl1" xml:lang="en-US" id="ions_CommercialMember_lbl1">Commercial [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl1" xlink:title="label: CommercialMember to ions_CommercialMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CommercialMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CommercialMember_lbl2" xml:lang="en-US" id="ions_CommercialMember_lbl2">Commercial Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CommercialMember" xlink:to="ions_CommercialMember_lbl2" xlink:title="label: CommercialMember to ions_CommercialMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_EplontersenJointDevelopmentRevenueMember" xlink:label="EplontersenJointDevelopmentRevenueMember" xlink:title="EplontersenJointDevelopmentRevenueMember" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl">Joint development revenue for eplontersen.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl1">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl1" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xml:lang="en-US" id="ions_EplontersenJointDevelopmentRevenueMember_lbl2">Eplontersen Joint Development Revenue [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="EplontersenJointDevelopmentRevenueMember" xlink:to="ions_EplontersenJointDevelopmentRevenueMember_lbl2" xlink:title="label: EplontersenJointDevelopmentRevenueMember to ions_EplontersenJointDevelopmentRevenueMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ResearchDevelopmentAndPatentExpense" xlink:label="ResearchDevelopmentAndPatentExpense" xlink:title="ResearchDevelopmentAndPatentExpense" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl">The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl1" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl1">Research, Development and Patent Expense</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl1" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ResearchDevelopmentAndPatentExpense_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ResearchDevelopmentAndPatentExpense_lbl2" xml:lang="en-US" id="ions_ResearchDevelopmentAndPatentExpense_lbl2">Research, development and patent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ResearchDevelopmentAndPatentExpense" xlink:to="ions_ResearchDevelopmentAndPatentExpense_lbl2" xlink:title="label: ResearchDevelopmentAndPatentExpense to ions_ResearchDevelopmentAndPatentExpense_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:label="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:title="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl">The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1">Debt Instrument, Convertible, Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2">Percentage of principal amount used as purchase price upon occurrence of fundamental change</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" xlink:to="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" xlink:title="label: DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange to ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CallSpread" xlink:label="CallSpread" xlink:title="CallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CallSpread_lbl" xml:lang="en-US" id="ions_CallSpread_lbl">The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl" xlink:title="label: CallSpread to ions_CallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CallSpread_lbl1" xml:lang="en-US" id="ions_CallSpread_lbl1">Call Spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl1" xlink:title="label: CallSpread to ions_CallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CallSpread_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CallSpread_lbl2" xml:lang="en-US" id="ions_CallSpread_lbl2">Cost of call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CallSpread" xlink:to="ions_CallSpread_lbl2" xlink:title="label: CallSpread to ions_CallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:label="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:title="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl">The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1">Debt Instrument, Convertible, Conversion Price including call spread</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2">Effective conversion price per share with call spread (in dollars per share)</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" xlink:to="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" xlink:title="label: DebtInstrumentConvertibleConversionPriceIncludingCallSpread to ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DebtInstrumentConvertibleSharesSubjectToConversion" xlink:label="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:title="DebtInstrumentConvertibleSharesSubjectToConversion" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl">The number of shares of common stock subject to conversion if the debt was converted to equity.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1">Debt Instrument, Convertible, Shares Subject to Conversion</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DebtInstrumentConvertibleSharesSubjectToConversion" xlink:to="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" xlink:title="label: DebtInstrumentConvertibleSharesSubjectToConversion to ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2" xml:lang="en-US" id="ions_DebtInstrumentConvertibleSharesSubjectToConversion_lbl2">Total shares of common stock subject to conversion (in shares)</link:label>
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    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotesMember" xlink:label="ConvertibleSeniorNotesMember" xlink:title="ConvertibleSeniorNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember_lbl">Includes 0% convertible senior notes due April 2026, 0.125% convertible senior notes due December 2024, and 1% convertible senior notes due November 2021.</link:label>
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    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember_lbl1">Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotesMember" xlink:to="ions_ConvertibleSeniorNotesMember_lbl1" xlink:title="label: ConvertibleSeniorNotesMember to ions_ConvertibleSeniorNotesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotesMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotesMember_lbl2">Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotesMember" xlink:to="ions_ConvertibleSeniorNotesMember_lbl2" xlink:title="label: ConvertibleSeniorNotesMember to ions_ConvertibleSeniorNotesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:label="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:title="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl">0.125 percent convertible senior notes due December 2024 that were issued under subscription agreements in December 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1">Convertible Senior Notes 0.125 Percent, Issued under Subscription Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl2">0.125% Convertible Senior Notes Issued under Subscription Agreements [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember to ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:label="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:title="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl">0.125 percent convertible senior notes due December 2024 that were issued in exchange for 1 percent notes in December 2019.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1">Convertible Senior Notes 0.125 Percent, Issued in Exchange for 1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2">0.125% Convertible Senior Notes Issued in Exchange for 1 Percent Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember to ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:label="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:title="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl">Development chemistry and manufacturing facility located in Oceanside, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xml:lang="en-US" id="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember" xlink:to="ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" xlink:title="label: DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember to ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:label="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:title="LesseeOperatingLeaseNumberOfOptionsToExtendLease" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl">The number of options to extend the lease under the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1">Lessee, Operating Lease, Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2">Number of options to extend lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfOptionsToExtendLease" xlink:to="ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" xlink:title="label: LesseeOperatingLeaseNumberOfOptionsToExtendLease to ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CarlsbadFacilityMember" xlink:label="CarlsbadFacilityMember" xlink:title="CarlsbadFacilityMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadFacilityMember_lbl" xml:lang="en-US" id="ions_CarlsbadFacilityMember_lbl">Office and laboratory space in a facility adjacent to the Company's manufacturing facility located in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember_lbl" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadFacilityMember_lbl1" xml:lang="en-US" id="ions_CarlsbadFacilityMember_lbl1">Carlsbad Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember_lbl1" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadFacilityMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadFacilityMember_lbl2" xml:lang="en-US" id="ions_CarlsbadFacilityMember_lbl2">Carlsbad Facility [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadFacilityMember" xlink:to="ions_CarlsbadFacilityMember_lbl2" xlink:title="label: CarlsbadFacilityMember to ions_CarlsbadFacilityMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_BostonOfficeSpaceMember" xlink:label="BostonOfficeSpaceMember" xlink:title="BostonOfficeSpaceMember" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_BostonOfficeSpaceMember_lbl" xml:lang="en-US" id="ions_BostonOfficeSpaceMember_lbl">Office space located in Boston, Massachusetts leased under non-cancelable operating lease entered into in the second quarter of 2018..</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember_lbl" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_BostonOfficeSpaceMember_lbl1" xml:lang="en-US" id="ions_BostonOfficeSpaceMember_lbl1">Boston Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember_lbl1" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_BostonOfficeSpaceMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_BostonOfficeSpaceMember_lbl2" xml:lang="en-US" id="ions_BostonOfficeSpaceMember_lbl2">Boston Office Space [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="BostonOfficeSpaceMember" xlink:to="ions_BostonOfficeSpaceMember_lbl2" xlink:title="label: BostonOfficeSpaceMember to ions_BostonOfficeSpaceMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_HeadquartersLocationInCarlsbadCaliforniaMember" xlink:label="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:title="HeadquartersLocationInCarlsbadCaliforniaMember" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl">Headquarters location located in Carlsbad, California.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xml:lang="en-US" id="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2">Headquarters Location in Carlsbad, California [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="HeadquartersLocationInCarlsbadCaliforniaMember" xlink:to="ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" xlink:title="label: HeadquartersLocationInCarlsbadCaliforniaMember to ions_HeadquartersLocationInCarlsbadCaliforniaMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LesseeOperatingLeasePeriodOfFreeRent" xlink:label="LesseeOperatingLeasePeriodOfFreeRent" xlink:title="LesseeOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1">Lessee, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2">Period of free rent under lease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeasePeriodOfFreeRent" xlink:to="ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" xlink:title="label: LesseeOperatingLeasePeriodOfFreeRent to ions_LesseeOperatingLeasePeriodOfFreeRent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended" xlink:label="LesseeOperatingLeaseNumberOfLeasesThatWereExtended" xlink:title="LesseeOperatingLeaseNumberOfLeasesThatWereExtended" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl">The number of leases whose term was extended under the lessee's operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfLeasesThatWereExtended" xlink:to="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl" xlink:title="label: LesseeOperatingLeaseNumberOfLeasesThatWereExtended to ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl1" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl1">Lessee, Operating Lease, Number of leases that were extended</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfLeasesThatWereExtended" xlink:to="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl1" xlink:title="label: LesseeOperatingLeaseNumberOfLeasesThatWereExtended to ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl2" xml:lang="en-US" id="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl2">Number of leases that were extended</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LesseeOperatingLeaseNumberOfLeasesThatWereExtended" xlink:to="ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl2" xlink:title="label: LesseeOperatingLeaseNumberOfLeasesThatWereExtended to ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_CarlsbadOfficeSpacesMember" xlink:label="CarlsbadOfficeSpacesMember" xlink:title="CarlsbadOfficeSpacesMember" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl">Additional office spaces in Carlsbad, California leased under non-cancelable operating lease.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl1" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl1">Carlsbad Office Spaces [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl1" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_CarlsbadOfficeSpacesMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_CarlsbadOfficeSpacesMember_lbl2" xml:lang="en-US" id="ions_CarlsbadOfficeSpacesMember_lbl2">Carlsbad Office Spaces [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="CarlsbadOfficeSpacesMember" xlink:to="ions_CarlsbadOfficeSpacesMember_lbl2" xlink:title="label: CarlsbadOfficeSpacesMember to ions_CarlsbadOfficeSpacesMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:label="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:title="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl">Number of lots of undeveloped land adjacent to the Company's headquarters in Carlsbad, California included in purchase and sale agreement.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:to="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" xlink:title="label: NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement to ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1">Number of lots of undeveloped land included in purchase and sale agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:to="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" xlink:title="label: NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement to ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl2" xml:lang="en-US" id="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl2">Number of lots of undeveloped land included in purchase and sale agreement</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement" xlink:to="ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl2" xlink:title="label: NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement to ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_SubleasedOfficeSpaceInBostonMember" xlink:label="SubleasedOfficeSpaceInBostonMember" xlink:title="SubleasedOfficeSpaceInBostonMember" />
    <link:label xlink:type="resource" xlink:label="ions_SubleasedOfficeSpaceInBostonMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_SubleasedOfficeSpaceInBostonMember_lbl" xml:lang="en-US" id="ions_SubleasedOfficeSpaceInBostonMember_lbl">Sublease of office space located in Boston, Massachusetts leased under non-cancelable sublease operating lease entered into in January 2022.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubleasedOfficeSpaceInBostonMember" xlink:to="ions_SubleasedOfficeSpaceInBostonMember_lbl" xlink:title="label: SubleasedOfficeSpaceInBostonMember to ions_SubleasedOfficeSpaceInBostonMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xml:lang="en-US" id="ions_SubleasedOfficeSpaceInBostonMember_lbl1">Subleased Office Space in Boston [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="SubleasedOfficeSpaceInBostonMember" xlink:to="ions_SubleasedOfficeSpaceInBostonMember_lbl1" xlink:title="label: SubleasedOfficeSpaceInBostonMember to ions_SubleasedOfficeSpaceInBostonMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AnotherOfficeSpaceInBostonMember" xlink:label="AnotherOfficeSpaceInBostonMember" xlink:title="AnotherOfficeSpaceInBostonMember" />
    <link:label xlink:type="resource" xlink:label="ions_AnotherOfficeSpaceInBostonMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AnotherOfficeSpaceInBostonMember_lbl" xml:lang="en-US" id="ions_AnotherOfficeSpaceInBostonMember_lbl">Another office space located in Boston, Massachusetts leased under non-cancelable operating lease entered into in September 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AnotherOfficeSpaceInBostonMember" xlink:to="ions_AnotherOfficeSpaceInBostonMember_lbl" xlink:title="label: AnotherOfficeSpaceInBostonMember to ions_AnotherOfficeSpaceInBostonMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AnotherOfficeSpaceInBostonMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AnotherOfficeSpaceInBostonMember_lbl1" xml:lang="en-US" id="ions_AnotherOfficeSpaceInBostonMember_lbl1">Another Office Space in Boston [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AnotherOfficeSpaceInBostonMember" xlink:to="ions_AnotherOfficeSpaceInBostonMember_lbl1" xlink:title="label: AnotherOfficeSpaceInBostonMember to ions_AnotherOfficeSpaceInBostonMember_lbl1" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LessorOperatingLeasePeriodOfFreeRent" xlink:label="LessorOperatingLeasePeriodOfFreeRent" xlink:title="LessorOperatingLeasePeriodOfFreeRent" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent_lbl">Period of time in which the lessor provides free rent under operating lease to the lessee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent_lbl" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1">Lessor, Operating Lease, Period of Free Rent</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_LessorOperatingLeasePeriodOfFreeRent_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_LessorOperatingLeasePeriodOfFreeRent_lbl2" xml:lang="en-US" id="ions_LessorOperatingLeasePeriodOfFreeRent_lbl2">Period of free rent under sublease</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="LessorOperatingLeasePeriodOfFreeRent" xlink:to="ions_LessorOperatingLeasePeriodOfFreeRent_lbl2" xlink:title="label: LessorOperatingLeasePeriodOfFreeRent to ions_LessorOperatingLeasePeriodOfFreeRent_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_AkceaTherapeuticsIncMember" xlink:label="AkceaTherapeuticsIncMember" xlink:title="AkceaTherapeuticsIncMember" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_AkceaTherapeuticsIncMember_lbl" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl">Akcea Therapeutics, Inc. is a subsidiary of the Company and was formed to develop and commercialize drugs for cardiometabolic disorders.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_AkceaTherapeuticsIncMember_lbl1" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl1">Akcea Therapeutics, Inc. [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl1" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_AkceaTherapeuticsIncMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_AkceaTherapeuticsIncMember_lbl2" xml:lang="en-US" id="ions_AkceaTherapeuticsIncMember_lbl2">Akcea [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="AkceaTherapeuticsIncMember" xlink:to="ions_AkceaTherapeuticsIncMember_lbl2" xlink:title="label: AkceaTherapeuticsIncMember to ions_AkceaTherapeuticsIncMember_lbl2" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotes1PercentMember" xlink:label="ConvertibleSeniorNotes1PercentMember" xlink:title="ConvertibleSeniorNotes1PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl">1 percent convertible senior notes due November 2021.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl1">Convertible Senior Notes 1 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl2">1% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes1PercentMember_lbl3">1 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes1PercentMember" xlink:to="ions_ConvertibleSeniorNotes1PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes1PercentMember to ions_ConvertibleSeniorNotes1PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotes0PercentMember" xlink:label="ConvertibleSeniorNotes0PercentMember" xlink:title="ConvertibleSeniorNotes0PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl">0 percent convertible senior notes due April 2026.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl1">Convertible Senior Notes 0 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl2">0 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0PercentMember_lbl3">0% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0PercentMember" xlink:to="ions_ConvertibleSeniorNotes0PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0PercentMember to ions_ConvertibleSeniorNotes0PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_ConvertibleSeniorNotes0125PercentMember" xlink:label="ConvertibleSeniorNotes0125PercentMember" xlink:title="ConvertibleSeniorNotes0125PercentMember" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl">0.125 percent convertible senior notes due December 2024.</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:role="http://www.xbrl.org/2003/role/label" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl1">Convertible Senior Notes 0.125 Percent [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl1" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl1" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:role="http://www.xbrl.org/2003/role/terseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl2">0.125 Percent Convertible Senior Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl2" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl2" />
    <link:label xlink:type="resource" xlink:label="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:role="http://www.xbrl.org/2003/role/verboseLabel" xlink:title="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xml:lang="en-US" id="ions_ConvertibleSeniorNotes0125PercentMember_lbl3">0.125% Notes [Member]</link:label>
    <link:labelArc xlink:type="arc" xlink:arcrole="http://www.xbrl.org/2003/arcrole/concept-label" xlink:from="ConvertibleSeniorNotes0125PercentMember" xlink:to="ions_ConvertibleSeniorNotes0125PercentMember_lbl3" xlink:title="label: ConvertibleSeniorNotes0125PercentMember to ions_ConvertibleSeniorNotes0125PercentMember_lbl3" />
    <link:loc xlink:type="locator" xlink:href="ions-20221231.xsd#ions_LongTermObligations" xlink:label="LongTermObligations" xlink:title="LongTermObligations" />
    <link:label xlink:type="resource" xlink:label="ions_LongTermObligations_lbl" xlink:role="http://www.xbrl.org/2003/role/documentation" xlink:title="ions_LongTermObligations_lbl" xml:lang="en-US" id="ions_LongTermObligations_lbl">Including the current and noncurrent portions, amount of long-term debt, lease obligations and other obligations.</link:label>
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<SEQUENCE>31
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end
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</DOCUMENT>
<DOCUMENT>
<TYPE>GRAPHIC
<SEQUENCE>32
<FILENAME>image6.jpg
<TEXT>
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<SEQUENCE>33
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368499776">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Document and Entity Information - USD ($)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Feb. 16, 2023</div></th>
<th class="th"><div>Jun. 30, 2022</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CoverAbstract', window );"><strong>Cover [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentType', window );">Document Type</a></td>
<td class="text">10-K<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AmendmentFlag', window );">Amendment Flag</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentAnnualReport', window );">Document Annual Report</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentPeriodEndDate', window );">Document Period End Date</a></td>
<td class="text">Dec. 31,  2022<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CurrentFiscalYearEndDate', window );">Current Fiscal Year End Date</a></td>
<td class="text">--12-31<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalYearFocus', window );">Document Fiscal Year Focus</a></td>
<td class="text">2022<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentFiscalPeriodFocus', window );">Document Fiscal Period Focus</a></td>
<td class="text">FY<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_DocumentTransitionReport', window );">Document Transition Report</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFileNumber', window );">Entity File Number</a></td>
<td class="text">000-19125<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityRegistrantName', window );">Entity Registrant Name</a></td>
<td class="text">Ionis Pharmaceuticals, Inc<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCentralIndexKey', window );">Entity Central Index Key</a></td>
<td class="text">0000874015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityIncorporationStateCountryCode', window );">Entity Incorporation, State or Country Code</a></td>
<td class="text">DE<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityTaxIdentificationNumber', window );">Entity Tax Identification Number</a></td>
<td class="text">33-0336973<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressAddressLine1', window );">Entity Address, Address Line One</a></td>
<td class="text">2855 Gazelle Court<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressCityOrTown', window );">Entity Address, City or Town</a></td>
<td class="text">Carlsbad<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressStateOrProvince', window );">Entity Address, State or Province</a></td>
<td class="text">CA<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityAddressPostalZipCode', window );">Entity Address, Postal Zip Code</a></td>
<td class="text">92010<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_CityAreaCode', window );">City Area Code</a></td>
<td class="text">760<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_LocalPhoneNumber', window );">Local Phone Number</a></td>
<td class="text">931-9200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_Security12bTitle', window );">Title of 12(b) Security</a></td>
<td class="text">Common Stock, $.001 Par Value<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_TradingSymbol', window );">Trading Symbol</a></td>
<td class="text">IONS<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_SecurityExchangeName', window );">Security Exchange Name</a></td>
<td class="text">NASDAQ<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityWellKnownSeasonedIssuer', window );">Entity Well-known Seasoned Issuer</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityVoluntaryFilers', window );">Entity Voluntary Filers</a></td>
<td class="text">No<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCurrentReportingStatus', window );">Entity Current Reporting Status</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityInteractiveDataCurrent', window );">Entity Interactive Data Current</a></td>
<td class="text">Yes<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityFilerCategory', window );">Entity Filer Category</a></td>
<td class="text">Large Accelerated Filer<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntitySmallBusiness', window );">Entity Small Business</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityEmergingGrowthCompany', window );">Entity Emerging Growth Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_IcfrAuditorAttestationFlag', window );">ICFR Auditor Attestation Flag</a></td>
<td class="text">true<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityShellCompany', window );">Entity Shell Company</a></td>
<td class="text">false<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityPublicFloat', window );">Entity Public Float</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,804,704,734<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_EntityCommonStockSharesOutstanding', window );">Entity Common Stock, Shares Outstanding</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">142,953,993<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorFirmId', window );">Auditor Firm ID</a></td>
<td class="text">42<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorName', window );">Auditor Name</a></td>
<td class="text">Ernst & Young LLP<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_dei_AuditorLocation', window );">Auditor Location</a></td>
<td class="text">San Diego, California<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AmendmentFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the XBRL content amends previously-filed or accepted submission.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AmendmentFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorFirmId">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>PCAOB issued Audit Firm Identifier</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorFirmId</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:nonemptySequenceNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorLocation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorLocation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:internationalNameItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_AuditorName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_AuditorName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:internationalNameItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CityAreaCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Area code of city</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CityAreaCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CoverAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cover page.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CoverAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_CurrentFiscalYearEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>End date of current fiscal year in the format --MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_CurrentFiscalYearEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gMonthDayItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentAnnualReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as an annual report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentAnnualReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalPeriodFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fiscal period values are FY, Q1, Q2, and Q3.  1st, 2nd and 3rd quarter 10-Q or 10-QT statements have value Q1, Q2, and Q3 respectively, with 10-K, 10-KT or other fiscal year statements having FY.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalPeriodFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fiscalPeriodItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentFiscalYearFocus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>This is focus fiscal year of the document report in YYYY format. For a 2006 annual report, which may also provide financial information from prior periods, fiscal 2006 should be given as the fiscal year focus. Example: 2006.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentFiscalYearFocus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:gYearItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentPeriodEndDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period.  The format of the date is YYYY-MM-DD.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentPeriodEndDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentTransitionReport">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true only for a form used as a transition report.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Forms 10-K, 10-Q, 20-F<br> -Number 240<br> -Section 13<br> -Subsection a-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentTransitionReport</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_DocumentType">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_DocumentType</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:submissionTypeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressAddressLine1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Address Line 1 such as Attn, Building Name, Street Name</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressAddressLine1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressCityOrTown">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the City or Town</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressCityOrTown</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressPostalZipCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Code for the postal or zip code</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressPostalZipCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityAddressStateOrProvince">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the state or province.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityAddressStateOrProvince</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:stateOrProvinceItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCentralIndexKey">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCentralIndexKey</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:centralIndexKeyItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate number of shares or other units outstanding of each of registrant's classes of capital or common stock or other ownership interests, if and as stated on cover of related periodic report. Where multiple classes or units exist define each class/interest by adding class of stock items such as Common Class A [Member], Common Class B [Member] or Partnership Interest [Member] onto the Instrument [Domain] of the Entity Listings, Instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityCurrentReportingStatus">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' whether registrants (1) have filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that registrants were required to file such reports), and (2) have been subject to such filing requirements for the past 90 days. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityCurrentReportingStatus</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityEmergingGrowthCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate if registrant meets the emerging growth company criteria.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityEmergingGrowthCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFileNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Commission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFileNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:fileNumberItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityFilerCategory">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate whether the registrant is one of the following: Large Accelerated Filer, Accelerated Filer, Non-accelerated Filer. Definitions of these categories are stated in Rule 12b-2 of the Exchange Act. This information should be based on the registrant's current or most recent filing containing the related disclosure.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityFilerCategory</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:filerCategoryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityIncorporationStateCountryCode">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Two-character EDGAR code representing the state or country of incorporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityIncorporationStateCountryCode</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarStateCountryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityInteractiveDataCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Regulation S-T<br> -Number 232<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityInteractiveDataCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityPublicFloat">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the price at which the common equity was last sold, or the average bid and asked price of such common equity, as of the last business day of the registrant's most recently completed second fiscal quarter.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityPublicFloat</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityRegistrantName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityRegistrantName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityShellCompany">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Boolean flag that is true when the registrant is a shell company as defined in Rule 12b-2 of the Exchange Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityShellCompany</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntitySmallBusiness">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates that the company is a Smaller Reporting Company (SRC).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntitySmallBusiness</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityTaxIdentificationNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b-2<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityTaxIdentificationNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:employerIdItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityVoluntaryFilers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityVoluntaryFilers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_EntityWellKnownSeasonedIssuer">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicate 'Yes' or 'No' if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Is used on Form Type: 10-K, 10-Q, 8-K, 20-F, 6-K, 10-K/A, 10-Q/A, 20-F/A, 6-K/A, N-CSR, N-Q, N-1A.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Securities Act<br> -Number 230<br> -Section 405<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_EntityWellKnownSeasonedIssuer</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:yesNoItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_IcfrAuditorAttestationFlag">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 10-K<br> -Number 249<br> -Section 310<br><br>Reference 2: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 20-F<br> -Number 249<br> -Section 220<br> -Subsection f<br><br>Reference 3: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Form 40-F<br> -Number 249<br> -Section 240<br> -Subsection f<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_IcfrAuditorAttestationFlag</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:booleanItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_LocalPhoneNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Local phone number for entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_LocalPhoneNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:normalizedStringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_Security12bTitle">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Title of a 12(b) registered security.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection b<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_Security12bTitle</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:securityTitleItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_SecurityExchangeName">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Name of the Exchange on which a security is registered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/presentationRef<br> -Publisher SEC<br> -Name Exchange Act<br> -Number 240<br> -Section 12<br> -Subsection d1-1<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_SecurityExchangeName</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:edgarExchangeCodeItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_dei_TradingSymbol">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Trading symbol of an instrument as listed on an exchange.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">dei_TradingSymbol</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>dei_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dei:tradingSymbolItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368732752">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED BALANCE SHEETS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrentAbstract', window );"><strong>Current assets:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsAtCarryingValue', window );">Cash and cash equivalents</a></td>
<td class="nump">$ 276,472<span></span>
</td>
<td class="nump">$ 869,191<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShortTermInvestments', window );">Short-term investments</a></td>
<td class="nump">1,710,397<span></span>
</td>
<td class="nump">1,245,782<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrent', window );">Contracts receivable</a></td>
<td class="nump">25,538<span></span>
</td>
<td class="nump">61,896<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNet', window );">Inventories</a></td>
<td class="nump">22,033<span></span>
</td>
<td class="nump">24,806<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsCurrent', window );">Other current assets</a></td>
<td class="nump">168,254<span></span>
</td>
<td class="nump">143,374<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsCurrent', window );">Total current assets</a></td>
<td class="nump">2,202,694<span></span>
</td>
<td class="nump">2,345,049<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="nump">74,294<span></span>
</td>
<td class="nump">178,069<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use assets</a></td>
<td class="nump">181,544<span></span>
</td>
<td class="nump">17,974<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAssetsNoncurrent', window );">Deposits and other assets</a></td>
<td class="nump">75,344<span></span>
</td>
<td class="nump">70,598<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Assets', window );">Total assets</a></td>
<td class="nump">2,533,876<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccountsPayableCurrent', window );">Accounts payable</a></td>
<td class="nump">17,921<span></span>
</td>
<td class="nump">11,904<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeRelatedLiabilitiesCurrent', window );">Accrued compensation</a></td>
<td class="nump">49,178<span></span>
</td>
<td class="nump">38,810<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Accrued liabilities</a></td>
<td class="nump">140,101<span></span>
</td>
<td class="nump">88,560<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedIncomeTaxesCurrent', window );">Income taxes payable</a></td>
<td class="nump">6,249<span></span>
</td>
<td class="nump">36<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityCurrent', window );">Current portion of deferred contract revenue</a></td>
<td class="nump">90,577<span></span>
</td>
<td class="nump">97,714<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilitiesCurrent', window );">Other current liabilities</a></td>
<td class="nump">7,535<span></span>
</td>
<td class="nump">3,526<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrent', window );">Total current liabilities</a></td>
<td class="nump">311,561<span></span>
</td>
<td class="nump">240,550<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityNoncurrent', window );">Long-term deferred contract revenue</a></td>
<td class="nump">287,768<span></span>
</td>
<td class="nump">351,879<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityNoncurrent', window );">Long-term lease liabilities</a></td>
<td class="nump">178,941<span></span>
</td>
<td class="nump">19,432<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermLoansFromBank', window );">Long-term mortgage debt</a></td>
<td class="nump">8,847<span></span>
</td>
<td class="nump">59,713<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilitiesNoncurrent', window );">Long-term obligations</a></td>
<td class="nump">7,126<span></span>
</td>
<td class="nump">6,946<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Liabilities', window );">Total liabilities</a></td>
<td class="nump">1,960,989<span></span>
</td>
<td class="nump">1,839,953<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockValue', window );">Common stock, $0.001 par value; 300,000,000 shares authorized, 142,057,736 and 141,210,015 shares issued and outstanding at December 31, 2022 and December 31, 2021, respectively</a></td>
<td class="nump">142<span></span>
</td>
<td class="nump">141<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdditionalPaidInCapitalCommonStock', window );">Additional paid-in capital</a></td>
<td class="nump">2,059,850<span></span>
</td>
<td class="nump">1,964,167<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax', window );">Accumulated other comprehensive loss</a></td>
<td class="num">(57,480)<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RetainedEarningsAccumulatedDeficit', window );">Accumulated deficit</a></td>
<td class="num">(1,429,625)<span></span>
</td>
<td class="num">(1,159,903)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquity', window );">Total stockholders' equity</a></td>
<td class="nump">572,887<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquity', window );">Total liabilities and stockholders' equity</a></td>
<td class="nump">2,533,876<span></span>
</td>
<td class="nump">2,611,690<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">622,242<span></span>
</td>
<td class="nump">619,119<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesCurrentAbstract', window );"><strong>Current liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtNoncurrent', window );">Convertible senior notes, net</a></td>
<td class="nump">$ 544,504<span></span>
</td>
<td class="nump">$ 542,314<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccountsPayableCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccountsPayableCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedIncomeTaxesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount as of the balance sheet date of the unpaid sum of the known and estimated amounts payable to satisfy all currently due domestic and foreign income tax obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(15)(b)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(15)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(20))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedIncomeTaxesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated change in equity from transactions and other events and circumstances from non-owner sources, net of tax effect, at period end. Excludes Net Income (Loss), and accumulated changes in equity from transactions resulting from investments by owners and distributions to owners. Includes foreign currency translation items, certain pension adjustments, unrealized gains and losses on certain investments in debt and equity securities, other than temporary impairment (OTTI) losses related to factors other than credit losses on available-for-sale and held-to-maturity debt securities that an entity does not intend to sell and it is not more likely than not that the entity will be required to sell before recovery of the amortized cost basis, as well as changes in the fair value of derivatives related to the effective portion of a designated cash flow hedge.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669686-108580<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e681-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdditionalPaidInCapitalCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value received from shareholders in common stock-related transactions that are in excess of par value or stated value and amounts received from other stock-related transactions. Includes only common stock transactions (excludes preferred stock transactions). May be called contributed capital, capital in excess of par, capital surplus, or paid-in capital.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdditionalPaidInCapitalCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Assets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are recognized. Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Assets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all assets that are expected to be realized in cash, sold, or consumed within one year (or the normal operating cycle, if longer). Assets are probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 4: 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3<br> -Subparagraph (bb)<br> -URI https://asc.fasb.org/extlink&amp;oid=123419778&amp;loc=d3e5710-111685<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iv))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 18: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 19: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrent</td>
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<tr>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AssetsCurrentAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashAndCashEquivalentsAtCarryingValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates. Excludes cash and cash equivalents within disposal group and discontinued operation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3044-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashAndCashEquivalentsAtCarryingValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate par or stated value of issued nonredeemable common stock (or common stock redeemable solely at the option of the issuer). This item includes treasury stock repurchased by the entity. Note: elements for number of nonredeemable common shares, par value and other disclosure concepts are in another section within stockholders' equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerAssetNetCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after allowance for credit loss, of right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130533-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerAssetNetCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebtNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying amount of long-term convertible debt as of the balance sheet date, net of the amount due in the next twelve months or greater than the normal operating cycle, if longer. The debt is convertible into another form of financial instrument, typically the entity's common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebtNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeRelatedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of the carrying values as of the balance sheet date of obligations incurred through that date and payable for obligations related to services received from employees, such as accrued salaries and bonuses, payroll taxes and fringe benefits. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeRelatedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Liabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Sum of the carrying amounts as of the balance sheet date of all liabilities that are recognized. Liabilities are probable future sacrifices of economic benefits arising from present obligations of an entity to transfer assets or provide services to other entities in the future.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19-26)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (d)<br> -URI 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10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Liabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities and equity items, including the portion of equity attributable to noncontrolling interests, if any.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 5: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(32))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquity</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total obligations incurred as part of normal operations that are expected to be paid during the following twelve months or within one business cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124433192&amp;loc=SL2890621-112765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(A))<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermLoansFromBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the operating cycle if longer, excluding current portion.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16)(a)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermLoansFromBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAssetsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncurrent assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(17))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAssetsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities classified as other, due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherLiabilitiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities classified as other, due after one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.24)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherLiabilitiesNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business to produce goods and services and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429447&amp;loc=SL124453093-239630<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RetainedEarningsAccumulatedDeficit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cumulative amount of the reporting entity's undistributed earnings or deficit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(23)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (h)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 40<br> -Section 65<br> -Paragraph 2<br> -Subparagraph (g)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=124501264&amp;loc=SL117420844-207641<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RetainedEarningsAccumulatedDeficit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShortTermInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investments including trading securities, available-for-sale securities, held-to-maturity securities, and short-term investments classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(1)(g))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShortTermInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquity">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of all stockholders' equity (deficit) items, net of receivables from officers, directors, owners, and affiliates of the entity which are attributable to the parent. The amount of the economic entity's stockholders' equity attributable to the parent excludes the amount of stockholders' equity which is allocable to that ownership interest in subsidiary equity which is not attributable to the parent (noncontrolling interest, minority interest). This excludes temporary equity and is sometimes called permanent equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SAB Topic 4.E)<br> -URI https://asc.fasb.org/extlink&amp;oid=122038336&amp;loc=d3e74512-122707<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(31))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(30))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 7: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 28<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=123596393&amp;loc=d3e14064-108612<br><br>Reference 8: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquity</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378606960">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares<br></strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityAbstract', window );"><strong>Stockholders' equity:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockParOrStatedValuePerShare', window );">Common stock, par value (in dollars per share)</a></td>
<td class="nump">$ 0.001<span></span>
</td>
<td class="nump">$ 0.001<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">142,057,736<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">142,057,736<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract', window );"><strong>LIABILITIES AND STOCKHOLDERS' EQUITY</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockParOrStatedValuePerShare">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face amount or stated value per share of common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockParOrStatedValuePerShare</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<td>dtr-types:perShareItemType</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:sharesItemType</td>
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<td>na</td>
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<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LiabilitiesAndStockholdersEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LiabilitiesAndStockholdersEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<head>
<title></title>
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<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367545376">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpensesAbstract', window );"><strong>Expenses:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfGoodsAndServicesSold', window );">Cost of sales</a></td>
<td class="nump">14,116<span></span>
</td>
<td class="nump">10,842<span></span>
</td>
<td class="nump">11,947<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ResearchDevelopmentAndPatentExpense', window );">Research, development and patent</a></td>
<td class="nump">833,147<span></span>
</td>
<td class="nump">643,453<span></span>
</td>
<td class="nump">535,077<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SellingGeneralAndAdministrativeExpense', window );">Selling, general and administrative</a></td>
<td class="nump">150,295<span></span>
</td>
<td class="nump">186,347<span></span>
</td>
<td class="nump">354,322<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Total operating expenses</a></td>
<td class="nump">997,558<span></span>
</td>
<td class="nump">840,642<span></span>
</td>
<td class="nump">901,346<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Loss from operations</a></td>
<td class="num">(410,191)<span></span>
</td>
<td class="num">(30,186)<span></span>
</td>
<td class="num">(172,082)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NonoperatingIncomeExpenseAbstract', window );"><strong>Other income (expense):</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentIncomeNet', window );">Investment income</a></td>
<td class="nump">25,331<span></span>
</td>
<td class="nump">10,044<span></span>
</td>
<td class="nump">30,562<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestExpense', window );">Interest expense</a></td>
<td class="num">(8,122)<span></span>
</td>
<td class="num">(9,349)<span></span>
</td>
<td class="num">(9,510)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnInvestments', window );">Gain (loss) on investments</a></td>
<td class="num">(7,333)<span></span>
</td>
<td class="nump">10,103<span></span>
</td>
<td class="nump">16,540<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets1', window );">Gain on sale of real estate assets</a></td>
<td class="nump">149,604<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherNonoperatingIncomeExpense', window );">Other expenses</a></td>
<td class="num">(7,274)<span></span>
</td>
<td class="num">(9,760)<span></span>
</td>
<td class="num">(62)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax benefit (expense)</a></td>
<td class="num">(257,985)<span></span>
</td>
<td class="num">(29,148)<span></span>
</td>
<td class="num">(134,552)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Income tax benefit (expense)</a></td>
<td class="num">(11,737)<span></span>
</td>
<td class="nump">551<span></span>
</td>
<td class="num">(345,191)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net loss</a></td>
<td class="num">(269,722)<span></span>
</td>
<td class="num">(28,597)<span></span>
</td>
<td class="num">(479,743)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest', window );">Net loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">35,480<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
<td class="num">$ (444,263)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
<td class="num">$ (3.18)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net loss per share (in dollars per share)</a></td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
<td class="num">$ (3.18)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net loss per share (in shares)</a></td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CommercialMember', window );">Commercial Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 303,358<span></span>
</td>
<td class="nump">$ 342,395<span></span>
</td>
<td class="nump">$ 364,699<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">242,314<span></span>
</td>
<td class="nump">267,776<span></span>
</td>
<td class="nump">286,583<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=us-gaap_ProductMember', window );">TEGSEDI and WAYLIVRA Revenue, Net [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">30,051<span></span>
</td>
<td class="nump">55,500<span></span>
</td>
<td class="nump">69,999<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_LicensingAndOtherRoyaltiesMember', window );">Licensing and Other Royalty Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">30,993<span></span>
</td>
<td class="nump">19,119<span></span>
</td>
<td class="nump">8,117<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">Research and Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">364,565<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_CollaborativeAgreementRevenueMember', window );">Collaborative Agreement Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">207,222<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">364,565<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_EplontersenJointDevelopmentRevenueMember', window );">Eplontersen Joint Development Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenuesAbstract', window );"><strong>Revenue:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 76,787<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ResearchDevelopmentAndPatentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects. Also includes charges for amortization and write-downs of capitalized patent costs, as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ResearchDevelopmentAndPatentExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostOfGoodsAndServicesSold">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs related to goods produced and sold and services rendered by an entity during the reporting period. This excludes costs incurred during the reporting period related to financial services rendered and other revenue generating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.2(a),(d))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfGoodsAndServicesSold</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CostsAndExpensesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostsAndExpensesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: 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-SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1252-109256<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 17: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e3842-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1252-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1337-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of assets, including but not limited to property plant and equipment, intangible assets and equity in securities of subsidiaries or equity method investee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized and unrealized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27405-111563<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(c),9(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/recommendedDisclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 940<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126941158&amp;loc=d3e41242-110953<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the cost of borrowed funds accounted for as interest expense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=6450988&amp;loc=d3e26243-108391<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (210.5-03(11))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04.9)<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentIncomeNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accretion (amortization) of discount (premium), and investment expense, of interest income and dividend income on nonoperating securities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.7(a),(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.8)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentIncomeNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of Net Income (Loss) attributable to noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NonoperatingIncomeExpenseAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherNonoperatingIncomeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (expense) related to nonoperating activities, classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.9)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherNonoperatingIncomeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenuesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenuesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SellingGeneralAndAdministrativeExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate total costs related to selling a firm's product and services, as well as all other general and administrative expenses. Direct selling expenses (for example, credit, warranty, and advertising) are expenses that can be directly linked to the sale of specific products. Indirect selling expenses are expenses that cannot be directly linked to the sale of specific products, for example telephone expenses, Internet, and postal charges. General and administrative expenses include salaries of non-sales personnel, rent, utilities, communication, etc.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SellingGeneralAndAdministrativeExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The average number of shares or units issued and outstanding that are used in calculating diluted EPS or earnings per unit (EPU), determined based on the timing of issuance of shares or units in the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1505-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of [basic] shares or units, after adjustment for contingently issuable shares or units and other shares or units not deemed outstanding, determined by relating the portion of time within a reporting period that common shares or units have been outstanding to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1448-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378605280">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract', window );"><strong>CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net loss</a></td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
<td class="num">$ (479,743)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax', window );">Unrealized gains (losses) on investments, net of tax</a></td>
<td class="num">(24,395)<span></span>
</td>
<td class="num">(11,486)<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Currency translation adjustment</a></td>
<td class="num">(417)<span></span>
</td>
<td class="num">(111)<span></span>
</td>
<td class="nump">617<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary', window );">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(127)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest', window );">Comprehensive loss</a></td>
<td class="num">(294,534)<span></span>
</td>
<td class="num">(40,194)<span></span>
</td>
<td class="num">(475,524)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest', window );">Comprehensive loss attributable to noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(35,480)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ComprehensiveIncomeNetOfTax', window );">Comprehensive loss attributable to Ionis Pharmaceuticals, Inc. common stockholders</a></td>
<td class="num">$ (294,534)<span></span>
</td>
<td class="num">$ (40,194)<span></span>
</td>
<td class="num">$ (440,044)<span></span>
</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Adjustments to other comprehensive income (loss) from purchase of noncontrolling interest of subsidiary.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income, attributable to parent entity. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(24))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e557-108580<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(26))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669619-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income (loss) and other comprehensive income (loss), attributable to noncontrolling interests. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669625-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(21))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669619-108580<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 21<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4613674-111683<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 8: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxAttributableToNoncontrollingInterest</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax of increase (decrease) in equity from transactions and other events and circumstances from net income and other comprehensive income. Excludes changes in equity resulting from investments by owners and distributions to owners.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669619-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(20))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569616-111683<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669625-108580<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(24))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ComprehensiveIncomeNetOfTaxIncludingPortionAttributableToNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=126980362&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after tax and before adjustment, of unrealized holding gain (loss) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale). Excludes unrealized gain (loss) on investment in debt security measured at amortized cost (held-to-maturity) from transfer to available-for-sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementOfIncomeAndComprehensiveIncomeAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>42
<FILENAME>R6.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366842128">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($)<br> shares in Thousands, $ in Thousands</strong></div></th>
<th class="th"><div>Common Stock [Member]</div></th>
<th class="th"><div>Additional Paid In Capital [Member]</div></th>
<th class="th"><div>Accumulated Other Comprehensive Loss [Member]</div></th>
<th class="th"><div>Accumulated Deficit [Member]</div></th>
<th class="th"><div>Total Ionis Stockholders' Equity [Member]</div></th>
<th class="th"><div>Noncontrolling Interest in Akcea Therapeutics, Inc. [Member]</div></th>
<th class="th"><div>Total</div></th>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2019</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">$ 1,985,650<span></span>
</td>
<td class="num">$ (25,290)<span></span>
</td>
<td class="num">$ (596,495)<span></span>
</td>
<td class="nump">$ 1,364,005<span></span>
</td>
<td class="nump">$ 213,454<span></span>
</td>
<td class="nump">$ 1,577,459<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2019</a></td>
<td class="nump">140,340<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(444,263)<span></span>
</td>
<td class="num">(444,263)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(444,263)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">617<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">52,033<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">52,034<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">52,034<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,721<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestDecreaseFromRedemptions', window );">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(324,022)<span></span>
</td>
<td class="nump">301<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(323,721)<span></span>
</td>
<td class="num">(220,965)<span></span>
</td>
<td class="num">(544,686)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue', window );">Repurchases and retirements of common stock</a></td>
<td class="num">$ (1)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,548)<span></span>
</td>
<td class="num">(90,549)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,549)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodShares', window );">Repurchases and retirements of common stock (in shares)</a></td>
<td class="num">(1,478)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(13,410)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(217)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment', window );">Deferred tax liability adjustment due to purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,714<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestPeriodIncreaseDecrease', window );">Noncontrolling interest in Akcea Therapeutics, Inc.</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(42,563)<span></span>
</td>
<td class="num">(428)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(42,991)<span></span>
</td>
<td class="nump">7,511<span></span>
</td>
<td class="num">(35,480)<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2020</a></td>
<td class="nump">$ 140<span></span>
</td>
<td class="nump">1,895,519<span></span>
</td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(1,131,306)<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2020</a></td>
<td class="nump">140,366<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(28,597)<span></span>
</td>
<td class="num">(28,597)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(28,597)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(11,486)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(11,486)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(11,486)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(111)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(111)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(111)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">11,563<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">11,564<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">11,564<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,132<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued', window );">Issuance of warrants</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther', window );">Purchase of note hedges</a></td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">120,678<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">120,678<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">120,678<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(16,725)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(16,725)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(16,725)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(288)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2021</a></td>
<td class="nump">$ 141<span></span>
</td>
<td class="nump">1,964,167<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
<td class="num">(1,159,903)<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2021</a></td>
<td class="nump">141,210<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward', window );"><strong>Increase (Decrease) in Stockholders' Equity [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(269,722)<span></span>
</td>
<td class="num">(269,722)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(269,722)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent', window );">Change in unrealized gains (losses), net of tax</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24,395)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24,395)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(24,395)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax', window );">Foreign currency translation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(417)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(417)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(417)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross', window );">Issuance of common stock in connection with employee stock plans</a></td>
<td class="nump">$ 1<span></span>
</td>
<td class="nump">6,372<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,373<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,373<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation', window );">Issuance of common stock in connection with employee stock plans (in shares)</a></td>
<td class="nump">1,194<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)</a></td>
<td class="num">(346)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance at Dec. 31, 2022</a></td>
<td class="nump">$ 142<span></span>
</td>
<td class="nump">$ 2,059,850<span></span>
</td>
<td class="num">$ (57,480)<span></span>
</td>
<td class="num">$ (1,429,625)<span></span>
</td>
<td class="nump">$ 572,887<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 572,887<span></span>
</td>
</tr>
<tr class="rc">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharesIssued', window );">Balance (in shares) at Dec. 31, 2022</a></td>
<td class="nump">142,058<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in additional paid in capital (APIC) due to deferred tax liability adjustment associated with the purchase of noncontrolling interest of Akcea Therapeutics, Inc.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AdjustmentsToAdditionalPaidInCapitalDeferredTaxLiabilityAdjustment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease to equity for grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of other increase (decrease) in additional paid in capital (APIC).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase to additional paid-in capital (APIC) for recognition of cost for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=126964447&amp;loc=d3e11149-113907<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 20<br> -Section 55<br> -Paragraph 13<br> -URI https://asc.fasb.org/extlink&amp;oid=126964447&amp;loc=d3e11178-113907<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 35<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126961718&amp;loc=d3e4534-113899<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in additional paid in capital (APIC) resulting from the issuance of warrants. Includes allocation of proceeds of debt securities issued with detachable stock purchase warrants.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 25<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=123466302&amp;loc=d3e4724-112606<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToAdditionalPaidInCapitalWarrantIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInStockholdersEquityRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestDecreaseFromRedemptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Decrease in noncontrolling interest (for example, but not limited to, redeeming or purchasing the interests of noncontrolling shareholders, issuance of shares (interests) by the non-wholly owned subsidiary to the parent entity for other than cash, and a buyback of shares (interest) by the non-wholly owned subsidiary from the noncontrolling interests).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 23<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569655-111683<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4616395-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestDecreaseFromRedemptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Net Increase or Decrease in balance of noncontrolling interest in the subsidiary during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4568740-111683<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments, of appreciation (loss) in value of unsold available-for-sale securities, attributable to parent entity. Excludes amounts related to other than temporary impairment (OTTI) loss.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569616-111683<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 45<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=126929396&amp;loc=SL4569643-111683<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of gain (loss) on foreign currency translation adjustments, foreign currency transactions designated and effective as economic hedges of a net investment in a foreign entity and intra-entity foreign currency transactions that are of a long-term-investment nature.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 20<br> -Section 35<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=123602790&amp;loc=d3e30304-110892<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 10<br> -Section 45<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=126980362&amp;loc=d3e28129-110885<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32022-110900<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10A<br> -Subparagraph (a-c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669646-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=d3e637-108580<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationGainLossArisingDuringPeriodNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of stock issued as of the balance sheet date, including shares that had been issued and were previously outstanding but which are now held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares used to settle grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number, after forfeiture, of shares or units issued under share-based payment arrangement. Excludes shares or units issued under employee stock ownership plan (ESOP).</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Value, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodValueShareBasedCompensationGross</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares that have been repurchased and retired during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedAndRetiredDuringPeriodShares</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockRepurchasedAndRetiredDuringPeriodValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Equity impact of the value of stock that has been repurchased and retired during the period. The excess of the purchase price over par value can be charged against retained earnings (once the excess is fully allocated to additional paid in capital).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockRepurchasedAndRetiredDuringPeriodValue</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367141424">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
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<tr>
<th class="th" colspan="2"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Mar. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net loss</a></td>
<td class="num">$ (52,430)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 224,613<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
<td class="num">$ (479,743)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract', window );"><strong>Adjustments to reconcile net loss to net cash provided by (used in) operating activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Depreciation', window );">Depreciation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14,328<span></span>
</td>
<td class="nump">15,487<span></span>
</td>
<td class="nump">13,365<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense', window );">Amortization of right-of-use operating lease assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,362<span></span>
</td>
<td class="nump">1,721<span></span>
</td>
<td class="nump">1,731<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfIntangibleAssets', window );">Amortization of other assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,415<span></span>
</td>
<td class="nump">2,352<span></span>
</td>
<td class="nump">2,064<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments', window );">Amortization of premium on investments, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7,389<span></span>
</td>
<td class="nump">17,776<span></span>
</td>
<td class="nump">11,521<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
<td class="nump">4,958<span></span>
</td>
<td class="nump">3,255<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensation', window );">Stock-based compensation expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100,264<span></span>
</td>
<td class="nump">120,678<span></span>
</td>
<td class="nump">230,117<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">8,627<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossOnDispositionOfAssets', window );">Non-cash losses related to disposal of property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">531<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SaleAndLeasebackTransactionGainLossNet', window );">Gain on sale of real estate assets</a></td>
<td class="num">(150,100)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(150,135)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RealizedInvestmentGainsLosses', window );">Gain on investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">224<span></span>
</td>
<td class="num">(1,092)<span></span>
</td>
<td class="num">(16,540)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxesAndTaxCredits', window );">Deferred income taxes, including changes in valuation allowance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">341,729<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived', window );">Non-cash losses related to other assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,030<span></span>
</td>
<td class="nump">2,707<span></span>
</td>
<td class="nump">1,948<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract', window );"><strong>Changes in operating assets and liabilities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset', window );">Contracts receivable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">36,358<span></span>
</td>
<td class="nump">14,308<span></span>
</td>
<td class="num">(13,170)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInInventories', window );">Inventories</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,773<span></span>
</td>
<td class="num">(2,841)<span></span>
</td>
<td class="num">(1,261)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets', window );">Other current and long-term assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(24,682)<span></span>
</td>
<td class="num">(877)<span></span>
</td>
<td class="num">(9,975)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncreaseDecreaseInIncomeTaxesReceivablePayable', window );">Long-term income taxes receivable (payable)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">1,008<span></span>
</td>
<td class="num">(89)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInAccountsPayable', window );">Accounts payable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,094<span></span>
</td>
<td class="num">(6,000)<span></span>
</td>
<td class="num">(2,755)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable', window );">Income taxes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,213<span></span>
</td>
<td class="num">(1,288)<span></span>
</td>
<td class="num">(31,190)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities', window );">Accrued compensation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,368<span></span>
</td>
<td class="num">(26,918)<span></span>
</td>
<td class="nump">28,371<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities', window );">Accrued liabilities and other current liabilities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">46,695<span></span>
</td>
<td class="num">(8,381)<span></span>
</td>
<td class="nump">32,424<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability', window );">Deferred contract revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(71,248)<span></span>
</td>
<td class="num">(82,829)<span></span>
</td>
<td class="num">(75,910)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInOperatingActivities', window );">Net cash provided by (used in) operating activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(274,370)<span></span>
</td>
<td class="nump">30,799<span></span>
</td>
<td class="nump">35,892<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract', window );"><strong>Investing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt', window );">Purchases of short-term investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1,485,772)<span></span>
</td>
<td class="num">(1,124,193)<span></span>
</td>
<td class="num">(1,570,410)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities', window );">Proceeds from sale of short-term investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">989,152<span></span>
</td>
<td class="nump">1,344,185<span></span>
</td>
<td class="nump">1,885,935<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment', window );">Purchases of property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(15,721)<span></span>
</td>
<td class="num">(11,955)<span></span>
</td>
<td class="num">(35,120)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">254,083<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireIntangibleAssets', window );">Acquisition of licenses and other assets, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(4,378)<span></span>
</td>
<td class="num">(5,946)<span></span>
</td>
<td class="num">(5,928)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireOtherInvestments', window );">Purchases of strategic investments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(7,185)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInInvestingActivities', window );">Net cash provided by (used in) investing activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(262,636)<span></span>
</td>
<td class="nump">194,906<span></span>
</td>
<td class="nump">274,477<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Proceeds from equity, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,373<span></span>
</td>
<td class="nump">11,565<span></span>
</td>
<td class="nump">52,036<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation', window );">Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(10,953)<span></span>
</td>
<td class="num">(16,725)<span></span>
</td>
<td class="num">(13,411)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromConvertibleDebt', window );">Proceeds from the issuance of 0 percent convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">632,500<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyMonetizationIssuanceCosts', window );">Royalty monetization issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(29)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsOfDebtIssuanceCosts', window );">0 percent convertible senior notes issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(15,609)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EarlyRepaymentOfConvertibleDebt', window );">Repurchase of $247.9 million principal amount of 1 percent convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(256,963)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repayment of remaining principal amount of 1 percent convertible senior notes at maturity</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(61,967)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(136,620)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForRepurchaseOfCommonStock', window );">Repurchases and retirements of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (90,500)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(90,548)<span></span>
</td>
<td class="num">$ (34,400)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Principal payments on debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(50,686)<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToMinorityShareholders', window );">Purchase of noncontrolling interest of Akcea Therapeutics, Inc., including cash payments for cancellation of Akcea Therapeutics, Inc. equity awards</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(544,686)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivities', window );">Net cash provided by (used in) financing activities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(55,295)<span></span>
</td>
<td class="nump">245,933<span></span>
</td>
<td class="num">(596,609)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations', window );">Effects of exchange rates on cash</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(418)<span></span>
</td>
<td class="num">(111)<span></span>
</td>
<td class="nump">617<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect', window );">Net increase (decrease) in cash and cash equivalents</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(592,719)<span></span>
</td>
<td class="nump">471,527<span></span>
</td>
<td class="num">(285,623)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at beginning of year</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 683,287<span></span>
</td>
<td class="nump">869,191<span></span>
</td>
<td class="nump">397,664<span></span>
</td>
<td class="nump">683,287<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents', window );">Cash and cash equivalents at end of year</a></td>
<td class="nump">$ 276,472<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 869,191<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">276,472<span></span>
</td>
<td class="nump">869,191<span></span>
</td>
<td class="nump">397,664<span></span>
</td>
<td class="nump">$ 683,287<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SupplementalCashFlowInformationAbstract', window );"><strong>Supplemental disclosures of cash flow information:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestPaidNet', window );">Interest paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,898<span></span>
</td>
<td class="nump">4,778<span></span>
</td>
<td class="nump">6,247<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxesPaid', window );">Income taxes paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,010<span></span>
</td>
<td class="nump">38<span></span>
</td>
<td class="nump">25,855<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract', window );"><strong>Supplemental disclosures of non-cash investing and financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability', window );">Right-of-use assets obtained in exchange for lease liabilities</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">168,931<span></span>
</td>
<td class="nump">6,641<span></span>
</td>
<td class="nump">2,149<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NonCashCapitalAndPatentExpenditures', window );">Amounts accrued for capital and patent expenditures</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 4,767<span></span>
</td>
<td class="nump">$ 705<span></span>
</td>
<td class="nump">$ 4,059<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="9"></td></tr>
<tr><td colspan="9"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.</td>
</tr></table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EarlyRepaymentOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the extinguishment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EarlyRepaymentOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInIncomeTaxesReceivablePayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in income taxes receivable (payable), which represents the amount due from tax authorities for refunds of overpayments or recoveries of income taxes paid or the amount due for taxes based on the reporting entity's earnings or attributable to the entity's income earning process (business presence) within a given jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInIncomeTaxesReceivablePayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NonCashCapitalAndPatentExpenditures">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Future cash outflow to pay for purchases of fixed assets and patents that have been incurred.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NonCashCapitalAndPatentExpenditures</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyMonetizationIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties in connection with a monetization transaction of future SPINRAZA and pelacarsen royalties the Company is entitled to under collaboration and licensing agreements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyMonetizationIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The sum of the periodic adjustments of the differences between securities' face values and purchase prices that are charged against earnings. This is called accretion if the security was purchased at a discount and amortization if it was purchased at premium. As a noncash item, this element is an adjustment to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccretionAmortizationOfDiscountsAndPremiumsInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AdjustmentsToReconcileNetIncomeLossToCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495355-112611<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate expense charged against earnings to allocate the cost of intangible assets (nonphysical assets not used in production) in a systematic and rational manner to the periods expected to benefit from such assets. As a noncash expense, this element is added back to net income when calculating cash provided by or used in operations using the indirect method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16323-109275<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=6388964&amp;loc=d3e16225-109274<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage. Excludes amount for disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3044-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=SL98516268-108586<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in cash, cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; including effect from exchange rate change. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123444420&amp;loc=d3e33268-110906<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashFlowNoncashInvestingAndFinancingActivitiesDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxesAndTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) and income tax credits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxesAndTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Depreciation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of expense recognized in the current period that reflects the allocation of the cost of tangible assets over the assets' useful lives. Includes production and non-production related depreciation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Depreciation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) from effect of exchange rate changes on cash and cash equivalents, and cash and cash equivalents restricted to withdrawal or usage; held in foreign currencies; including, but not limited to, disposal group and discontinued operations. Cash includes, but is not limited to, currency on hand, demand deposits with banks or financial institutions, and other accounts with general characteristics of demand deposits. Cash equivalents include, but are not limited to, short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 230<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123444420&amp;loc=d3e33268-110906<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectOfExchangeRateOnCashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsIncludingDisposalGroupAndDiscontinuedOperations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossOnDispositionOfAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale or disposal of property, plant and equipment assets, excluding oil and gas property and timber property.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 45<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126905981&amp;loc=d3e2443-110228<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=109226691&amp;loc=d3e2941-110230<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossOnDispositionOfAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ImpairmentOfIntangibleAssetsFinitelived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of impairment loss recognized in the period resulting from the write-down of the carrying amount of a finite-lived intangible asset to fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 350<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=66006027&amp;loc=d3e16373-109275<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ImpairmentOfIntangibleAssetsFinitelived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxesPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of cash paid during the current period to foreign, federal, state, and local authorities as taxes on income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=d3e4297-108586<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxesPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInAccountsPayable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate amount of liabilities incurred (and for which invoices have typically been received) and payable to vendors for goods and services received that are used in an entity's business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInAccountsPayable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in right to consideration in exchange for good or service transferred to customer when right is conditioned on something other than passage of time.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 310<br> -Section 45<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126938201&amp;loc=d3e55415-109406<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the amounts payable to taxing authorities for taxes that are based on the reporting entity's earnings, net of amounts receivable from taxing authorities for refunds of overpayments or recoveries of income taxes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInIncomeTaxesPayableNetOfIncomeTaxesReceivable</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInInventories">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in the aggregate value of all inventory held by the reporting entity, associated with underlying transactions that are classified as operating activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInInventories</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOperatingCapitalAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOperatingCapitalAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The increase (decrease) during the reporting period in other obligations or expenses incurred but not yet paid.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherAccountsPayableAndAccruedLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in employer-related costs classified as other and current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherEmployeeRelatedLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncreaseDecreaseInOtherOperatingAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in operating assets classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncreaseDecreaseInOtherOperatingAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPaidNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash paid for interest, excluding capitalized interest, classified as operating activity. Includes, but is not limited to, payment to settle zero-coupon bond for accreted interest of debt discount and debt instrument with insignificant coupon interest rate in relation to effective interest rate of borrowing attributable to accreted interest of debt discount.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126999549&amp;loc=d3e4297-108586<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 17<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3367-108585<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPaidNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from financing activities, including discontinued operations. Financing activity cash flows include obtaining resources from owners and providing them with a return on, and a return of, their investment; borrowing money and repaying amounts borrowed, or settling the obligation; and obtaining and paying for other resources obtained from creditors on long-term credit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from investing activities, including discontinued operations. Investing activity cash flows include making and collecting loans and acquiring and disposing of debt or equity instruments and property, plant, and equipment and other productive assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInInvestingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow (outflow) from operating activities, including discontinued operations. Operating activity cash flows include transactions, adjustments, and changes in value not defined as investing or financing activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3536-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 24<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3521-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetCashProvidedByUsedInOperatingActivitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense for right-of-use asset from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for a financial contract that meets the hedge criteria as either cash flow hedge, fair value hedge or hedge of net investment in foreign operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForRepurchaseOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to reacquire common stock during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForRepurchaseOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsOfDebtIssuanceCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow paid to third parties in connection with debt origination, which will be amortized over the remaining maturity period of the associated long-term debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsOfDebtIssuanceCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to satisfy grantee's tax withholding obligation for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsRelatedToTaxWithholdingForShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to acquire investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3151-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to acquire asset without physical form usually arising from contractual or other legal rights, excluding goodwill.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireOtherInvestments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to acquire investments classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireOtherInvestments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow associated with the acquisition of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale; includes cash outflows to pay for construction of self-constructed assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToMinorityShareholders">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to a noncontrolling interest. Includes, but not limited to, reduction of noncontrolling interest ownership. Excludes dividends paid to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToMinorityShareholders</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the issuance of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfWarrants">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfWarrants</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from sale, maturity, prepayment and call of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3151-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3179-108585<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26853-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleAndMaturityOfAvailableForSaleSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3179-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(g)(1)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669619-108580<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (a)(1)<br> -URI 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-Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 27: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 28: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 29: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 30: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 31: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591551-111686<br><br>Reference 32: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 33: 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RealizedInvestmentGainsLosses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of realized gain (loss) on investment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04.3(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RealizedInvestmentGainsLosses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in right-of-use asset obtained in exchange for operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SaleAndLeasebackTransactionGainLossNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale and leaseback transaction from transfer of asset accounted for as sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 40<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128295416&amp;loc=SL77919786-209982<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SaleAndLeasebackTransactionGainLossNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of noncash expense for share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SupplementalCashFlowInformationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378368480">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
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<tr class="rh">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
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<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetCashProvidedByUsedInFinancingActivitiesAbstract', window );"><strong>Financing activities:</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 247.9<span></span>
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<td class="nump">$ 247.9<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 375.6<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of the original debt instrument that was repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630376658000">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock', window );">Organization and Significant Accounting Policies</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">1. Organization and Significant Accounting Policies</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below
    100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the
    period the changes occurred<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Organization and Business Activity</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us
    to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> determine which elements of the collaboration
      reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we
      consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our eplontersen collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue;
    while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as SG&amp;A expense and research and development expense, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the
    following criteria:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
            contract; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the performance obligations</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We frequently enter into a collaboration agreement in which
      we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We
      evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we
      grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant
      discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do
    not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation. Refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Eplontersen Collaboration with AstraZeneca</span>, below for further discussion of a collaboration that included an upfront license payment.</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
        agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments,
        license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the
        payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount
      method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include
      a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our
      milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain.</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the
      stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present
      value. The significant inputs we use to determine the projected income of a license could include</span>:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of research and development, or R&amp;D, services by using our internal estimates of the cost to
    perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting
    guidance requires us to include a markup for a reasonable profit margin.</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based
      on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given
      period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires
      us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement
        and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services
        are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the
        amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative-effect adjustment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 Strategic Neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Our Revenue Sources</span></span>&#160;</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are sources of revenue and when we typically recognize revenue.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from
      SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began
    commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As
    a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and
    WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics
    companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In
    the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as
    distributors.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of
    the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
    view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
    distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer
    obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as
    selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as
    discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaboration agreements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services and manufacturing services.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>. For each collaboration, we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation
      is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they
      are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in
      the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when
      we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
      recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone to the
      transaction price.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the
    milestone event and we do not have a performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">License fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is
      because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not
      have any performance obligations related to the sublicense.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration with AstraZeneca</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the
    U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities
    that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca
    related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within one </span><span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a">quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022,
    approximately 82.5 percent of our contracts receivables were from one significant customer. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two
    significant customers.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen
    for SPINRAZA royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2022 and 2021, we recognized $73.5 million and $98.1 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the
    services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in research and development expenses are costs associated with our
    partner agreements. In 2022, 2021 and 2020, patent expenses were $4.7 million, $5.3 million and $4.1 million, respectively.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign
    subsidiaries. </div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing the total net loss attributable to our common stockholders by our weighted-average number
    of common shares outstanding during the period. For the years ended December 31, 2022 and 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the years ended December 31, 2022 and 2021 was $1.90 and $0.20, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the year ended December 31, 2020, we calculated total net loss attributable to our common stockholders using our net loss for Ionis on
    a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea. As a result of
    this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share was different than net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of
    operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.45</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111,775</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(197,762</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(246,702</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(444,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3.18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent
    shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock underlying the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022 and 2021, common stock underlying the following would also have had an anti-dilutive effect on net
    loss per share:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes; and</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of December 31, 2022 and 2021, we had warrants related to our 0 percent and 0.125 percent Notes outstanding. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended
    December 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected
    term based on our historical exercise patterns.</div>

<div><br/>
  </div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted to our board of directors after June 2020 fully vest after one year.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span> of the PRSUs may vest at the end
    of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the
    date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the
    second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the
    date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217;
      Equity,</span> for additional information regarding our stock-based compensation plans.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Merger
      in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span>68 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>77 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of
      Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Merger, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line in our
      statements of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheets. In addition, through the closing of the Akcea Merger, we recorded a noncontrolling interest adjustment to account for the stock options Akcea
      granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
      compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other Comprehensive Loss</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):</span></div>

<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,395</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,486</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(417</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(127</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive income (losses) for the year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,812</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,597</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,219</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(57,480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<div>
    <table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; text-align: right;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;</div>
          </td>

  </tr>


</table>
    </div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we
      received as part of a technology license or partner agreement. At December 31, 2022, we held equity investments in three publicly traded companies and eight
      privately held companies.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment
    of the same issuer.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in
    inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and,
    as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We
    expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial
    medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical
    write-offs.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,061</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,699</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,760</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,109</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,033</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left;"><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated Useful</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Lives (in years)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,351</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,158</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144,046</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,077</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,357</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,144</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,575</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">153,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">257,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less accumulated depreciation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(102,653</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,725</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">155,007</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,569</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,294</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,069</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we sold the facilities and related land at our headquarters for net proceeds of $202.6 million in connection with a sale and leaseback transaction.&#160; In connection with the sale of these real estate assets, we de-recognized the related land and improvements,
    building and building improvements, which resulted in a net gain of $150.1 million that we reported in other income (expense) in our consolidated
    statements of operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accrued Liabilities</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Clinical expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116,460</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,730</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In-licensing expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,945</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,044</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Commercial expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,498</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,471</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other miscellaneous expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,198</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,315</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total accrued liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">140,101</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88,560</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Costs</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, we had two
    outstanding convertible senior notes, our 0% Notes, which mature in April 2026, and our 0.125% Notes, which mature in December 2024. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, for further details on our convertible senior notes.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives
      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify the
    note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an
    aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_33bc30118e9548358994c912eadf2161">single</span> operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities
    subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity
    securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter
    of 2022. This guidance did not have a material impact on our consolidated financial statements.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
<span></span>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630376662768">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentTextBlock', window );">Investments</a></td>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2. Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2022:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span>
            or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span>
            but within <span style="text-indent: 0pt;">two years</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As illustrated above, at December 31, 2022,
    98 percent of our available-for-sale securities had a maturity of less than two years.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At December 31, 2022, we had an ownership interest of less than 20 percent </span>in eight
    privately held companies and three publicly held companies with which we conduct business<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2022</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,790</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,365</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">509,448</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133,585</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,829</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131,756</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">512,655</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">507,554</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,484</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,816</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,008</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,223,522</div>
        </td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,211,568</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">217,502</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,339</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,040</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,299</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">245,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,109</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">240,921</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(329</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,101</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">525,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(15,621</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">509,823</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,748,836</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27,639</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,721,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,372</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,911</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,783,848</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,451</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,997</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,772,302</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(226</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,493</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,494</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,360</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,770</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,778</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">612,557</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">792</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(345</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">613,004</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,644</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">379,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,935</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(561</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,374</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,635</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(500</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,274</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,909</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">471</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,966</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">635,120</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,172</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,311</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,248,124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,512</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,852</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,527</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash
            equivalents in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $7.7 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized
              non-cash loss in our consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.</span>&#160;</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus
            or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in our consolidated balance
              sheets.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be
      temporarily impaired at&#160;</span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands).
      All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more
      likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,136</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,629</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">305,367</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,879</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">689,503</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,508</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93,862</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(538</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,331</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,869</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">616,826</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,082</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,325</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">703,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,117</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(225</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,465</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(790</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,582</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,015</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,112,941</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,474</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">499,383</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,165</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,612,324</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27,639</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for investment.</p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630374199328">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresTextBlock', window );">Fair Value Measurements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">3. Fair Value Measurements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2022 and 2021&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. As of December 31, 2022, we did not have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy
    of the valuation techniques we utilized to determine the respective securities&#8217; fair value (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,655</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,655</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">726,950</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">726,950</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,055</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,055</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">748,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">748,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,917</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,917</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,943,585</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">970,669</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">972,916</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,875</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,807,528</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our
            consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$11.0 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets in our
            consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$2.3 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Convertible Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our 0.125% Notes and 0% Notes had a fair value of $498.9 million and $587.3 million at December 31, 2022,
    respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.</div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630379754400">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">4. Long-Term Obligations and Commitments</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0 percent</span>
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">622,242</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619,119</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0.125 percent</span>
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">544,504</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">186,156</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,058</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60,054</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,295</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,505</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,369,195</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,050</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,535</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,526</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,361,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,247,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0 Percent
    Convertible Senior Notes and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we completed a $632.5
    million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
    we had the following 0% Notes outstanding (in millions except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_ca0956ae2da341f1b584cfebcf6fbda4">April 2026</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion
    price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost
    us $46.9 million, of which $136.7
    million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0%
    Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">0.125 Percent
    Convertible Senior Notes and Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain
    holders of our existing 1% Notes to exchange $375.6
    million of our 1% Notes for $439.3
    million of our 0.125% Notes, and to issue $109.5
    million of our 0.125% Notes.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
    we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0.125% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_823fe367bb0d42249b87ea8d290aa62a">December 2024</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">83.28</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">123.38</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In conjunction with the issuance of our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes in December 2019, we entered into a call spread transaction, which
      was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our </span>0.125%
    Notes by increasing the effective conversion price on our 0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. We increased our effective conversion price to $</span>123.38<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> with the same number of underlying shares as our </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes. The call spread cost us $</span>52.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, of
      which $</span>108.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million was for the note hedge purchase,
      offset by $</span>56.1<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million we received for selling the
      warrants. Similar to our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, our note hedges are
      subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The note hedges will expire upon maturity of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. The holders of the </span>0.125% Notes<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> do not have any rights with respect to the note hedges and warrants.</span></div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Significant Accounting Policies</span>, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1 Percent
    Convertible Senior Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2021, we repurchased $247.9
    million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Other Terms of Convertible Senior Notes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The 0% and 0.125% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The 1% Notes were subject to similar terms.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2022, 2021 and 2020 included $5.3 million, $4.9 million and $3.2 million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Financing Arrangements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Operating Facilities</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In July 2017, we purchased the building that houses our primary R&amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase
    of these two facilities with mortgage debt of $60.4
    million in total. Our primary R&amp;D facility mortgage had an interest rate of 3.88 percent. Our manufacturing facility mortgage has an
    interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August 2027. We repaid
    our primary R&amp;D facility mortgage in October 2022 in conjunction with a sale and leaseback transaction.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell,
    subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our
    headquarters, which includes our primary R&amp;D facility, for a total purchase price of $263.4 million and we expect to receive total proceeds
    of $33.0 million upon the close of the sale of the two
    lots. We used a portion of the sale proceeds to extinguish our outstanding mortgage debt on our primary R&amp;D facility of $51.3 million.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Debt Maturity Schedules</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2022 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,281</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550,107</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">595</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">633,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">447</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,194,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,526</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,175,725</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Royalty Revenue Monetization</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone
    payments. Under the terms of the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027,
    increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In addition, Royalty Pharma will receive 25 percent of
    any future royalty payments on pelacarsen, our medicine in development for lipoprotein(a), or Lp(a), driven cardiovascular disease. Royalty Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma
    reach either $475 million or $550
    million, depending on the timing and occurrence of FDA approval of pelacarsen. We will begin accounting for the royalty monetization agreement in the first quarter of 2023.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeasesTextBlock', window );">Long-Term Obligations and Commitments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Operating Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Carlsbad Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases. In September 2022, we
    exercised our option to extend one of these leases, extending our term from January 2023 to May 2027. We have no remaining options to extend this lease. Our other office space lease in Carlsbad has an initial term ending in 2023.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed above in the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Financing Arrangements</span>, we lease our headquarters, which includes our primary R&amp;D facility, as part of a sale and leaseback transaction that closed in October 2022. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for 2
    additional terms of five years each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $280 million. In connection with the sale
    of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;D
    facility for us on those lots. Once this new facility is completed, our lease will commence.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Oceanside Lease</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside,
    California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#8217;s interior space.
    We will lease the facility for an initial term of 20 years and 3 months with options to extend the lease for two additional terms of 10 years each. The lease
    will commence when the lessor&#8217;s construction is complete and we are able to begin constructing tenant improvements.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Boston Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an
    additional five-year term. Under the lease agreement, we received a three-month free rent period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement
    date was in January 2022 when the office space was ready for our tenant&#8217;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending 83 months following the sublease commencement date with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced on January 6, 2022. We will receive lease payments over the sublease term totaling $9.6 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in November 2021.
    We are leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and
    an option to extend the lease for <span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c">an</span> additional five-year
    term. Under the lease agreement, we received a seven-month free rent period, which commenced on November 1, 2021. Our lease payments over the
    initial term total $6.8 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">181.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">186.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.8 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022,
    2021, and 2020 we paid $4.0 million, $3.3 million and $3.8 million of lease payments, which were included in operating activities in our consolidated statements of cash flows.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,640</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,781</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,800</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">196,911</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">299,594</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(113,438</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,215</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,941</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Rent expense was $8.3 million,
    $3.4 million and $3.7 million for the
    years ended December 31, 2022, 2021
    and 2020, respectively. </div>
<span></span>
</td>
</tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for information about short-term and long-term debt arrangements, which includes amounts of borrowings under each line of credit, note payable, commercial paper issue, bonds indenture, debenture issue, own-share lending arrangements and any other contractual agreement to repay funds, and about the underlying arrangements, rationale for a classification as long-term, including repayment terms, interest rates, collateral provided, restrictions on use of assets and activities, whether or not in compliance with debt covenants, and other matters important to users of the financial statements, such as the effects of refinancing and noncompliance with debt covenants.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -URI https://asc.fasb.org/subtopic&amp;trid=77888251<br></p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630376777840">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityNoteAbstract', window );"><strong>Stockholders' Equity [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityNoteDisclosureTextBlock', window );">Stockholders' Equity</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">5. Stockholders</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"> Equity</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Preferred Stock</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are authorized to issue up to 15
    million shares of &#8220;blank check&#8221; Preferred Stock. As of December 31, 2022, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2022.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Common Stock</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022 and 2021, we had 300 million shares of common
    stock authorized, of which 142.1 million and 141.2 million were issued and outstanding, respectively. As of December 31, 2022,
    total common shares reserved for future issuance were 43.2 million.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022,
    2021 and 2020, we issued 1.2 million, 1.1 million and 1.7 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $6.4 million, $11.6
    million and $52.0 million in 2022,
    2021 and 2020, respectively.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Share Repurchase Program</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2019, our board of directors approved a share repurchase program of up to $125 million of our common stock. In 2019, we repurchased 535,000 shares for $34.4 million. In the first quarter of 2020, we repurchased an additional 1.5 million shares for $90.5 million.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Plans</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1989 Stock Option Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides
    for the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees,
    directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the
    repricing. Options vest over a four-year period, with 25percent exercisable at the end of one year from the date of the grant and the
    balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2022, a total of 12 thousand options were outstanding, of which
    options to purchase 12 thousand shares were exercisable, and 65 thousand shares were available for future grant under the 1989 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2011 Equity Incentive Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the
    issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from
    our stockholders, we amended our 2011 Equity Incentive Plan, or<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> 2011 Plan,</span> to increase the total number of shares reserved for issuance. We increased the shares
    available under our 2011 Equity Incentive Plan from 5.5 million to 11.0 million in June 2015, from 11.0 million to 16.0 million in May 2017 and from 16.0 million to 23.0 million in June 2019. In the second quarter of 2021, after receiving approval from our stockholders, we amended our <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from </span>23.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>29.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and added a fungible share counting ratio whereby the share reserve will be reduced by </span>1.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and increased by
    </span>1.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> shares for each share of common stock returning from a
      full value award. </span>The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights
    that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only stock options, RSU
    and PRSU awards to our employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant
    and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a
    term of ten years. We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2022, a
    total of 13.7 million options were outstanding, of which 9.4 million were exercisable, 2.7 million restricted stock unit awards were
    outstanding, and 5.8 million shares were available for future grant under the 2011 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If one of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins three months before and ends twelve months following a change in control of the company, the impacted employee&#8217;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the termination date.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2020 Equity Incentive Plan</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In connection with the Akcea Merger in October 2020, we
      assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020
      Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to </span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment
      to the 2020 Plan. The amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately </span>2.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>1.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. We assumed the 2020 Plan in connection with Ionis&#8217; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2022, a total of 0.3 million
    options were outstanding, of which 61 thousand were exercisable, 0.1 million restricted stock unit awards were outstanding, and 1.2 million shares were
    available for future grant under the 2020 Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Corporate Transactions and Change in Control under 2011 and 2020 Plans</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
            acquiring corporation (or its parent company);</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2002 Non-Employee Directors&#8217; Stock Option Plan</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992
    Non-Employee Directors&#8217; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#8217; Stock Option Plan, or
    the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2 million to 2.0 million. In June 2020, after receiving approval from our
    stockholders, we further amended our 2002 Plan. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The amendments included:</span></div>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">An increase to the total number of shares reserved for issuance under the plan from </span>2.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million to </span>2.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million shares;</span></div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A reduction to the amount of the automatic awards under the plan;</div>
        </td>

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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A revision to the vesting schedule of new awards granted; and</div>
        </td>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">An extension of the term of the plan.</div>
        </td>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Options under this plan expire 10 years
    from the date of grant. At December 31, 2022, a total of 0.9 million options were outstanding, of which 0.8 million were exercisable, 0.1 million restricted stock unit awards were outstanding, and 0.6
    million shares were available for future grant under the 2002 Plan.</div>

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<div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Employee Stock Purchase Plan</div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2022. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10percent of each employee&#8217;s compensation)
    at the lower of 85percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended
    and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2022, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $28.57 per share. At December 31, 2022, there were 0.5 million shares available for purchase under the
    ESPP.</div>

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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock Option Activity</div>

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  </div>

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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2022 (in thousands, except per share and contractual life data):</div>

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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Exercise</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Price Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Remaining</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contractual Term</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Years)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Aggregate</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Intrinsic</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2021</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,089</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.04</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,864</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34.78</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(123</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29.35</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited/expired</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,860</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.96</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,970</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.57</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.01</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,243</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.74</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.56</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,651</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The weighted-average estimated fair values of options granted were $18.66, $24.35 and $29.43 for the years ended December 31, 2022, 2021 and 2020, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2022, 2021 and 2020 were $1.4 million, $2.5 million and $15.5 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $3.6 million, $8.5 million and $43.7 million for the years ended December 31, 2022, 2021 and 2020, respectively. For the year
    ended December 31, 2022, the weighted-average fair value of options exercised was $40.71. As of December 31, 2022, total unrecognized compensation cost related to
    non-vested stock options was $41.1 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Restricted Stock Unit Activity</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2021</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,618</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.05</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,401</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36.14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(958</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.05</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(295</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.61</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,766</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.30</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
    2021 and 2020, the
    weighted-average grant date fair value of RSUs granted was $36.14, $57.02 and $60.57 per RSU, respectively. As of December 31, 2022, total unrecognized compensation cost related to RSUs was $45.8 million. We expect to recognize this cost over a weighted average period of 1.2
    years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Performance Restricted Stock Unit Activity</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2021</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.20</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.28</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(16</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.03</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
    2021 and 2020, the
    weighted-average grant date fair value of PRSUs granted was $42.28, $77.17 and $93.09 per PRSU, respectively. As of December 31, 2022, total unrecognized compensation cost related to PRSUs was $2.4 million. We expect to recognize this cost over a weighted average period of 0.9
    years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-based Compensation Expense and Valuation Information</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">533</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">456</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,991</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73,704</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115,584</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,700</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,678</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">230,117</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2020, as part of the Akcea Merger, Akcea&#8217;s outstanding equity awards vested under Akcea&#8217;s Plan. As a result, in 2020, we
    recognized all unrecognized stock-based compensation, which totaled $59.3 million, under Akcea&#8217;s Plan.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization
      and Significant Accounting Policies</span>, for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022,
    2021 and 2020, we used the
    following weighted-average assumptions in our Black-Scholes calculations:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.7 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Risk-Free Interest Rate.</span> We base
    the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Dividend Yield.</span> We base the
    dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Volatility.</span> We use an average of
    the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Expected Life. </span>The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from <span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"><span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad">seven</span></span> to ten years for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended December 31, 2022. Under the simplified method, we calculate the
    expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Forfeitures.</span> We reduce stock-based
    compensation expense for estimated forfeitures. We estimate forfeitures at the time of grant and revise, if necessary, in subsequent periods if actual forfeitures differ from those estimates. We estimate forfeitures based on historical experience. </div>
<span></span>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368314576">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">6. Income Taxes</div>

<div><br/>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes is comprised of (in thousands):</div>

<div><br/>
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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">United States</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(258,493</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,966</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(137,222</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">508</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">818</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,670</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,148</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(134,552</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>

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  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(200</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(690</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,782</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">339</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">518</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,463</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">341,728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred income tax benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">341,728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">345,191</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The
    sources and tax effects of the differences are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,148</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(134,552</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Statutory rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(54,177</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,121</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,256</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State income tax net of federal benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,622</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,278</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37,705</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(49</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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  </tr>

  <tr>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred tax true-up</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(206</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,838</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,951</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17.4</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,931</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">193</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,030</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.4</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(16.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,435</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Impacts from Akcea Merger</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(22,032</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,503</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">345,191</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(256.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>


</table>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
    financial reporting purposes and the amounts used for income tax purposes.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2022 and 2021 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87,802</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,600</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">277,436</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">269,538</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,700</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,330</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,983</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,649</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,384</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,681</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense limitation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,996</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">119,635</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,119</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,813</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,929</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">858,014</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">706,346</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,303</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,504</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,159</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(313</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">808,722</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">697,773</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(808,722</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(697,773</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate our deferred tax assets regularly to determine whether adjustments to the valuation allowance are appropriate due to changes in facts or
    circumstances, such as changes in expected future pre-tax earnings, tax law, interactions with taxing authorities and developments in case law. In making this evaluation, we rely on our recent history of pre-tax earnings. Our material assumptions are
    our forecasts of future pre-tax earnings and the nature and timing of future deductions and income represented by the deferred tax assets and liabilities, all of which involve the exercise of significant judgment. Although we believe our estimates are
    reasonable, we are required to use significant judgment in determining the appropriate amount of valuation allowance recorded against our deferred tax assets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our valuation allowance increased by $111
    million from December 31, 2021 to December 31, 2022.
    The increase was primarily related to increases in our deferred tax asset for capitalized research and development expenses.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022, we had
    federal and state, primarily California, tax net operating loss carryforwards of $242.8 million and $461.3 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2022, we also had federal and California research and development tax credit carryforwards of $224.9 million and $110.7 million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2035. Our California research and development tax credit carryforwards are available indefinitely.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in
      thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,163</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,784</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(267</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(695</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,154</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">259</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,490</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,354</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,510</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,567</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,163</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in the balance of unrecognized tax benefits at December 31, 2022, 2021 and 2020 was $6.2 million, $6.2 million and $6.4 million respectively, that if we recognized, could impact our
    effective tax rate, subject to our remaining valuation allowance.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We estimate that it is reasonably possible that the balance of our gross unrecognized tax benefits may decrease by approximately $15.0 million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to tax credits.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2022, 2021 and 2020, we recognized $0.8 million, $0.5 million and $0.3 million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are subject to taxation in the U.S. and various state and foreign jurisdictions. The tax years 2018 through 2021 remain open to
    examination by major taxing jurisdictions, primarily federal and California, although net operating loss and credit carryforwards generated prior to 2018 may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if
    they have been used in an open period or are used in a future period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We do not provide for a U.S. income tax liability and foreign
      withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with
      these earnings</span>.</div>
<span></span>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630376733776">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CollaborativeArrangementDisclosureTextBlock', window );">Collaborative Arrangements and Licensing Agreements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">7. Collaborative Arrangements and Licensing Agreements</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Strategic Partnership</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Biogen</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological
    disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#8217;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with
    spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, AS, AD<sub>&#160;</sub>and
    Parkinson&#8217;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 31, 2022, we have received more than $3.4 billion from our
    Biogen collaborations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Spinal Muscular Atrophy Collaborations</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">SPINRAZA</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2012, we entered into a collaboration agreement
      with Biogen to develop and commercialize SPINRAZA.</span>&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we earned more than $</span>1.8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in total revenue under our SPINRAZA collaboration, including more than $</span>1.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> billion in revenue from SPINRAZA royalties and more than $</span>425<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in R&amp;D revenue. We are receiving tiered royalties ranging from
    </span>11 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>15 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from
      Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all global development,
      regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under our collaboration in 2016</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. Royalty
    Pharma&#8217;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen, which Novartis is developing. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">New antisense medicines for the treatment of SMA</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2017, we entered into a collaboration agreement
      with Biogen to </span>identify <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">new antisense medicines for the treatment of SMA</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen has the option to license therapies arising out of this collaboration following the completion of
      preclinical studies. Upon licensing, Biogen </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">will be responsible for global development, regulatory and commercialization activities and costs for such therapies</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. Under the collaboration agreement, we received a </span>$25
    million<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> upfront payment in the </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">fourth</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">2017</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In December 2021, we earned a $</span>60<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee payment when Biogen exercised its option to license ION306. </span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will receive development and regulatory milestone payments from Biogen if new medicines, including ION306, advance towards marketing approval.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $1.2 billion, which is comprised of a $25 million upfront payment, up to $110 million in license fees, up to $80 million in
    development milestone payments, up to $180 million in regulatory milestone payments, up to $800 million in sales milestone payments and other payments, including up to $555
    million if Biogen advances ION306, which includes up to $45 million in development milestone payments, up to $110 million in regulatory milestone payments and up to $400
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">from the mid-teens to </span>mid-20 percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span> From
    inception through December 31, 2022, we received $85 million in payments under this collaboration. We will achieve the next payment of up to $45 million<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for the initiation of a Phase 3 trial under this collaboration. </span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we
    completed our R&amp;D services performance obligation under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2021, we identified another performance obligation upon Biogen&#8217;s license of ION306 because the license we granted
    to Biogen is distinct from our other performance obligations. We recognized the $60 million license fee for ION306 as revenue at that time
    because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is solely responsible for the costs
    and expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;">Neurology Collaborations</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2018 Strategic Neurology</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In April 2018, we and Biogen entered into a strategic
      collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to
      develop therapies for these diseases for </span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> years. We are
      responsible for the identification of antisense drug candidates based on selected medicines</span>. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Biogen will have the option to license the selected medicine </span>after it completes the IND-enabling toxicology study. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">If Biogen exercises its
      option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In the </span>second<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> quarter of </span>2018<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we received </span>$1 billion from Biogen, comprised of $625 million
    to purchase our stock at an approximately 25 percent cash premium and $375 million in an upfront payment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of our collaboration, w<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">e are eligible to receive up to $</span>270<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span>15<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>105<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments and up to $</span>150<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments for each medicine that achieves marketing approval. </span>In addition, we are eligible to receive tiered royalties <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">up to the </span>20 percent range <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">on net sales.</span>&#160;<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">W</span>e are currently advancing multiple programs under
    this collaboration and from inception through December 31, 2022, we have received nearly $1.1 billion in payments under this collaboration. We will achieve the next payment of $7.5
    million if Biogen designates or advances another program<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">under this collaboration. </span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">At the commencement of this collaboration, we considered that
      the collaboration agreement and SPA were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. W</span>e
    identified one performance obligation, which was to perform R&amp;D services for Biogen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> We determined our transaction price to be $</span>552<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, comprised of $</span>375<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million from the
      upfront payment and $</span>177<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the premium paid by
      Biogen for its purchase of our common stock.</span> We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our
    valuation of the premium because Biogen received restricted shares of our common stock. We allocated the transaction price to our single performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From inception through December 31, 2022,
    we have included $616 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">in payments in the transaction price
      for our R&amp;D services performance obligation under this collaboration, including $</span>23<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2021 and $</span>11<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million of milestone payments we achieved in 2020. These milestone payments did not create new performance obligations because they are part of our original R&amp;D services performance obligation. Therefore, we included
      these amounts in our transaction price for our R&amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;D services performance obligation as we perform services based on our
      effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2013 Strategic Neurology</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the
    treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this
    collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen has the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to
    include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing five investigational medicines in development under this collaboration, including <span style="-sec-ix-hidden:Fact_864d03b225ca4f548971b12e6b3ad3d0">a</span> medicine for Parkinson&#8217;s disease (ION859), two medicines for ALS (tofersen and
    ION541), <span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460">a</span> medicine for multiple system atrophy (ION464) and <span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29">a</span> medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in registration for SOD1 ALS.
    As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for tofersen.</div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all medicines developed under this collaboration, with the specific amounts dependent upon the
    modality of the molecule advanced by Biogen. Under this collaboration, we received a $35 million license fee payment when Biogen licensed
    tofersen from us in 2018.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration for tofersen, we are eligible to receive nearly $110 million, which is comprised of the $35 million license fee received in 2018, up to
    $18 million in development milestone payments and up to $55 million in regulatory milestone payments. For each of the other antisense molecules that are chosen for drug discovery and development under this collaboration, we are eligible to receive up
    to approximately $260 million, which is comprised of a $70 million license fee, up to $60 million in development milestone payments, including
    amounts related to the cost of clinical trials, and up to $130 million in regulatory milestone payments. In addition, we are eligible to receive
    tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 31, 2022,
    we have received more than $300 million in payments under this collaboration. We will achieve the next payment of $16 million if the FDA approves Biogen&#8217;s NDA filing of tofersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of our 2013 strategic neurology collaboration, we identified one performance obligation, which was to perform R&amp;D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;D services, we include these amounts in our
    transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our
    performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>During 2020, we completed our remaining<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> research and development
      services and recognized the remaining revenue related to this performance obligation. </span>From inception through the completion of our R&amp;D services performance obligation in 2020, we included $145 million in total payments in the transaction price for our R&amp;D services performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under this collaboration, we have also generated additional
      payments that we concluded were not part of our R&amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in the third quarter of 2022, we earned a </span>$9&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">million milestone payment when the FDA accepted Biogen&#8217;s NDA filing of tofersen, which we recognized in full because we did not have any performance obligations related to this milestone payment.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">2012 Neurology</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat
    neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through
    the completion of the first Phase 2 study for each program. Under this collaboration, Biogen is conducting the IONIS-MAPT<sub>Rx</sub> study for AD and we are currently advancing ION582 for AS. If Biogen exercises its option to license a medicine, it
    will assume global development, regulatory and commercialization responsibilities and costs for that medicine.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Under the terms of the agreement, we received an upfront
      payment of $</span>30<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. Over the term of the collaboration,
      we are eligible to receive up to $</span>210<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is
      comprised of a $</span>70<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestone payments per program and up to $</span>130<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestone payments per program, plus a mark-up on the
      cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales of any medicines resulting from each of the </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> programs. From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span>170<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration, including nearly $</span>20<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments we received from Biogen for advancing ION582 and a $</span>10<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone payment we received from Biogen when Biogen advanced </span>IONIS-MAPT<sub>Rx</sub><sub>&#160;</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">during 2022. We will achieve the next payment of up to $</span>25<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>million if Biogen advances a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration, we determined we had a performance obligation to perform R&amp;D services. We allocated $40 million in total payments to the transaction price for our R&amp;D services performance obligation. In the third quarter of 2019, we completed our
    R&amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the
    total effort expected to satisfy our performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">When we commenced development for IONIS-MAPT<sub>Rx</sub> we identified our development work as a separate performance obligation. In the
    fourth quarter of 2022, we completed our R&amp;D services performance obligation for IONIS-MAPT<sub>Rx</sub>. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected
    to satisfy our performance obligation. From inception through December 31, 2022, we have included $57 million in the transaction price for our IONIS-MAPT<sub>Rx</sub> development performance obligation, including $19.5 million of milestone payments we earned from Biogen in 2020 when we advanced IONIS-MAPT<sub>Rx</sub>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#8217;s license of IONIS-MAPT<sub>Rx</sub> because the
    license we granted to Biogen is distinct from our other performance obligations. We recognized the $45 million license fee for IONIS-MAPT<sub>Rx</sub>
    as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is
    responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT<sub>Rx</sub>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter of 2022, we <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">achieved $</span>14.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in milestone payments when Biogen advanced ION582. </span>We will
    recognize revenue as we perform services based on our effort to satisfy our R&amp;D services performance obligation relative to the total effort expected to satisfy our performance obligation<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for ION582.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">242.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">267.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">428.8</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">408.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>351.2<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>407.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, respectively, related to our relationship with Biogen.</span></div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Joint Development and Commercialization Arrangement</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in
    Latin America.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. The agreement also includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to
    receive up to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization activities
    that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the 55 percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a
    reduction of our commercial and medical affairs expenses.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We will achieve the next payment of up to $50
    million upon the first regulatory approval under this collaboration. From inception through December 31, 2022, we have received nearly $260 million in payments under this collaboration.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research and Development Partners</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">AstraZeneca</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In addition to our collaboration for eplontersen, we have a collaboration with AstraZeneca focused on the treatment of cardiovascular,
    renal and metabolic diseases. In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us, including medicines in development to treat people with ATTR amyloidosis, a genetically associated form of kidney disease and <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">NASH</span>. AstraZeneca is
    responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $5.8 billion, which is comprised of a $65 million upfront payment, up to $290 million in license fees, up to $1.1 billion
    in development milestone payments, up to $2.9 billion in regulatory milestone payments and up to $1.5 billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully
    commercializes under this collaboration agreement. We will achieve the next payment of $10 million under this collaboration if AstraZeneca
    advances a medicine under this collaboration<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span> From inception through December 31, 2022, we have received more than $280 million in payments under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;D services performance obligation as we performed services
    based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> completed our performance obligation
      in</span> the fourth quarter of 2021. As we achieved milestone payments for our R&amp;D services, we included these amounts in our transaction price for our R&amp;D services performance obligation. From inception through the completion of our
    performance obligation, we have included $90 million in payments in the transaction price for our R&amp;D services performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth
    quarter of 2021, we earned a $30 million license fee when AstraZeneca licensed a target for a metabolic disease. We recognized the license fee as
    revenue at that time because AstraZeneca had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to AstraZeneca.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">254.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2022 and 2021.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">GSK</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In March 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK currently includes two medicines targeting hepatitis B virus, or HBV: bepirovirsen and IONIS-HBV-L<sub>Rx</sub>. We designed these medicines to reduce the production of viral proteins associated with HBV
    infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to $42.5 million in development milestone payments, up to $120
    million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops bepirovirsen. In
    addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2022,
    we have received more than $50 million in payments under the HBV program collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We completed our R&amp;D services performance obligations
      under our collaboration in the first quarter of 2015. </span>We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the
    license was distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that
    time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and
    royalties as GSK advances the HBV program.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> In January 2023, we earned a $</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million milestone when GSK initiated a Phase 3 study of bepirovirsen. We will achieve the next payment of $</span>15<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if the FDA accepts an NDA filing of bepirovirsen for review.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with GSK at December 31, 2022 and 2021.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Novartis</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In January 2017, we initiated a collaboration with Novartis
      to develop and commercialize pelacarsen and olezarsen.</span> Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in
    the fourth quarter 2019.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>In connection with Novartis&#8217; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would
    negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales
    of pelacarsen.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;When Novartis decided to not exercise its option for </span>olezarsen, we retained rights to develop and commercialize olezarsen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a $150 million license fee, a $25 million
    development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">From inception through </span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, we have received nearly $</span>275<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in payments under this collaboration. </span>We are also eligible to receive tiered royalties in the
    mid-teens to low 20 percent range on net sales of pelacarsen. In August 2021, we earned a $25 million milestone payment from Novartis when Novartis achieved 50 percent
    enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We recognized the milestone payment in full in the third quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment.
    <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> will achieve the next payment of up to $</span>75<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Novartis advances regulatory
      activities for pelacarsen.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100
    million in the first quarter of 2017.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified four separate performance obligations:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D services for pelacarsen;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D services for olezarsen;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">API for pelacarsen; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">API for olezarsen.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that the R&amp;D services for each medicine and the API for each medicine were distinct performance obligations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined our transaction price to be $108.4
    million, comprised of the following:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$75 million from the upfront payment;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$28.4 million for the premium paid by Novartis for its purchase
            of our common stock at a premium in the first quarter of 2017; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$5.0 million for the potential premium Novartis would have paid
            if they purchased our common stock in the future.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$</span>64.0<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million for the R&amp;D services for pelacarsen;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$40.1 million for the R&amp;D services for <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">olezarsen</span>; </div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$1.5</span>
            million for the delivery of pelacarsen API; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">$2.8</span>
            million for the delivery of olezarsen API.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We completed our R&amp;D services performance obligations for olezarsen and pelacarsen<sub>&#160;</sub>in 2019. As such, we recognized all
    revenue we allocated to the olezarsen and pelacarsen<sub>&#160;</sub>R&amp;D services as of the end of 2019.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognized revenue related to the R&amp;D services for
      pelacarsen and olezarsen performance obligations as we performed services </span>based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with Novartis at December 31, 2022 and 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As described in the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Biogen SPINRAZA</span>
    section above, in January 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term Obligations and Commitments</span>, for further discussion of this agreement.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Roche</div>

<div><br/>
  </div>

<div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Huntington&#8217;s Disease</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In April 2013, we formed an alliance with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people with
      early-stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for
      tominersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment, a $45 million license fee, up to $70 million in
    development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any product
    resulting from this alliance. From inception through December 31, 2022, we have received more than $150 million in payments under this collaboration. We will achieve the next payment of $17.5
    million if Roche advances a medicine under this collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;D services, we included these amounts in our
    transaction price for our R&amp;D services performance obligation. We recognized revenue for our R&amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2019, we earned $35 million in milestone payments when Roche advanced tominersen under this collaboration. In March 2021, Roche decided to discontinue dosing in the Phase 3
    GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche
    is focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under
    this collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> for Complement-Mediated Diseases</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2018, we entered into a collaboration agreement with Roche to<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> develop IONIS-FB-L</span><sub>Rx</sub> for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in two disease indications for <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">IONIS-FB-L</span><sub>Rx</sub>, one for the treatment of patients with GA, the advanced stage of dry AMD, and a <span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89">second</span> for the treatment of patients with IgA nephropathy.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">After positive data from a Phase 2 clinical study, </span>Roche<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> licensed IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">July 2022</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">for $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding. In July 2022, we amended our IONIS-FB-L</span><sub>Rx</sub><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that
      would require adjustments to revenue we previously recognized.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Over the term of the collaboration, we are eligible to
      receive more than $</span>810<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million, which is comprised of a $</span>75<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million upfront payment, a $</span>35<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million license fee, up to $</span>145<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in development milestones, up to $</span>279<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in regulatory milestones and up to $</span>280<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high
      teens to </span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> on net sales.</span><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>From inception through December 31, 2022,
    we have received more than $130 million in payments under this collaboration. <span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We will achieve the next payment of up to $</span>90<span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million if Roche advances IONIS-FB-L</span><sub><span style="background-color: #FBFBFB;">Rx</span></sub><span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> under this collaboration.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;D services for Roche. We determined the transaction price to be the $75 million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;D services performance obligation as we perform services
    based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;</span>We<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> currently estimate we will satisfy our performance obligation in </span>the third quarter of 2024.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our </span>consolidated balance sheets at December 31<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span>2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> and </span>2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> included deferred
      revenue of $</span>22.4<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million and $</span>31.6<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million related to our relationship with Roche, respectively.</span></div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Commercialization Partnerships</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Swedish Orphan Biovitrum AB (Sobi)</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution
    agreements with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each
    medicine.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PTC Therapeutics</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">In August 2018, we entered into an exclusive license
      agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-</span>20 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> range on net sales for each medicine. </span>In December 2021, we started receiving
    royalties from PTC for TEGSEDI sales<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Technology Enhancement Collaborations</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Bicycle License Agreement</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2020, we entered into a collaboration agreement with Bicycle and obtained an option to license its peptide technology to
    potentially increase the delivery capabilities of our LICA medicines. In July 2021, we paid $42 million when we exercised our option to license
    Bicycle&#8217;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for one year. In 2021, we recorded a $7.2 million equity investment for the
    shares we received in Bicycle. We recognized the remaining $34.8 million as R&amp;D expense in 2021. From inception through December 31, 2022, we have paid Bicycle $46.6
    million under this collaboration agreement.</div>

<div><br/>
  </div>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Metagenomi License Agreement</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In November 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize
    investigational medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid $80 million to license Metagenomi&#8217;s technologies. We recorded the $80 million payment as
    R&amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. We will also pay Metagenomi certain fees for the selection of genetic targets, and contingent on the
    achievement of certain development, regulatory and sales events, milestone payments and royalties. In addition, we will reimburse Metagenomi for certain of its costs in conducting its research and drug discovery activities under the collaboration.</div>

<div><br/>
  </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Other Agreements</div>

<div><br/>
    </div>

<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Alnylam Pharmaceuticals, Inc.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, Alnylam gave us a
      technology access fee, participation in fees from Alnylam&#8217;s partnering programs, as well as future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to 4 therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism
      and target-specific intellectual property for oligonucleotides against four targets, including FXI and Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against four other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#8217;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Alnylam (in millions, except percentage amounts):</div>

<div><br/>
    </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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  </tr>

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          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have any
    deferred revenue from our relationship with Alnylam at December 31, 2022 and 2021.</div>
<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for collaborative arrangements in which the entity is a participant, including a) information about the nature and purpose of such arrangements; b) its rights and obligations thereunder; c) the accounting policy for collaborative arrangements; and d) the income statement classification and amounts attributable to transactions arising from the collaborative arrangement between participants.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 808<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=6931272&amp;loc=SL5834143-161434<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 808<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=6931272&amp;loc=SL5834143-161434<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 808<br> -URI https://asc.fasb.org/topic&amp;trid=5833765<br></p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378620448">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">8. Employment Benefits</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $20,500 and $27,000 in 2022 for employees under 50 years old and employees 50 years old or over,
    respectively. We made approximately $5.6 million, $5.5
    million and $5.7 million in matching contributions for the years ended December 31, 2022, 2021 and 2020, respectively.</div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for retirement benefits.</p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630376777840">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LegalMattersAndContingenciesTextBlock', window );">Legal Proceedings</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">9. Legal Proceedings</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
    status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
    any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
    amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On August 5, 2021, </span>four<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> purported former stockholders of Akcea filed an action in the Delaware
      Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#8217;s board of directors; and
      (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary
      duties in connection with the October 2020 take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any
      other lawsuit that may be filed challenging the October 2020 take-private transaction is uncertain. Accordingly, on June 3, 2022, the parties reached an agreement in principle to settle the Delaware Action for $</span>12.5<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million. A Stipulation and Agreement of Compromise, Settlement and
      Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on July 5, 2022. On October 11, 2022, the Delaware Court of Chancery entered an Order and
      Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction,
      compromise and release of all claims that were asserted in the Delaware Action. The Order contains no admission of wrongdoing on the part of any of the Defendants. We recorded a net settlement expense of $</span>7.7<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> million within other expense in the accompanying consolidated statements of operations in 2022.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>January 19, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0059<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Shumacher Action. The complaint names Ionis&#8217; board of directors, or the
      Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also
      asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#8217; fees and costs, and such other relief as deemed just and
      proper by the court. On </span>March 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Ionis and the Board moved to dismiss the complaint. On May 24, 2022, the parties entered into a Stipulation and Agreement of
      Compromise, Settlement and Release.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>May 25, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. </span>No<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. </span>2022-0453<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, or the Cohen Action. The complaint names the Board as defendants and names Ionis
      as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive
      non-executive director compensation for the years </span>2018, 2019<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, and </span>2020<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. On </span>June
    2, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On </span>July 5, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">On </span>July 18, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, Ionis filed a Form </span>8<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of
      Action. On </span>September 21, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action
      plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. On February 7, 2023, the parties entered into
      an Amended Stipulation and Agreement of Compromise, Settlement and Release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.</span></div>
<span></span>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited)<br></strong></div></th>
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<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">10. Fourth Quarter Financial Data (Unaudited)</div>

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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion
    of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2022 and 2021 are as follows (in thousands, except per share data).</div>

<div><br/>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">151,890</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">440,006</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">359,909</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">219,403</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(208,019</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">220,603</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52,430</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,613</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income (loss) per share (4) (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net income (loss) per share (4) (6)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $80 million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31, 2021</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our ESPP</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">0 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">777</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,936</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">0.125 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">1 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders, plus assumed conversions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226,210</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160,340</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The entire disclosure for quarterly financial data. Includes, but is not limited to, tabular presentation of financial information for fiscal quarters, effect of year-end adjustments, and an explanation of matters or transactions that affect comparability of the information.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -URI https://asc.fasb.org/topic&amp;trid=2126967<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1B<br> -URI https://asc.fasb.org/extlink&amp;oid=126900988&amp;loc=SL124452896-108306<br></p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368238464">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies (Policies)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract', window );"><strong>Organization and Significant Accounting Policies [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConsolidationPolicyTextBlock', window );">Basis of Presentation</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basis of Presentation</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#8220;we&#8221;, &#8220;us&#8221; or &#8220;our&#8221;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea&#8217;s common stock below
    100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the
    period the changes occurred<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UseOfEstimates', window );">Use of Estimates</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Use of Estimates</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us
    to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock', window );">Revenue Recognition</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Revenue Recognition</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements</span>, or ASC 808. <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC </span>808<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> that contain multiple elements, we </span>first<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> determine which elements of the collaboration
      reflect a vendor-customer relationship and therefore are within the scope of ASC </span>606<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">, </span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Revenue from Contracts with Customers</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we
      consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our eplontersen collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue;
    while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as SG&amp;A expense and research and development expense, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Steps to Recognize Revenue</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">1.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the contract</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the
    following criteria:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We and our partner approved the contract and we are both committed to perform our obligations;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have identified our rights, our partner&#8217;s rights and the payment terms;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
            contract; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We believe collectability of the consideration is probable.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">2.</span></td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Identify the performance obligations</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We frequently enter into a collaboration agreement in which
      we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We
      evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we
      grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant
      discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do
    not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation. Refer to the section titled, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Eplontersen Collaboration with AstraZeneca</span>, below for further discussion of a collaboration that included an upfront license payment.</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">3.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Determine the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
        agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments,
        license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the
        payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.</div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount
      method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include
      a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our
      milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain.</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">4.</td>

    <td style="width: auto; vertical-align: top; text-align: left;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Allocate the transaction price</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We may engage a </span>third<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the
      stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present
      value. The significant inputs we use to determine the projected income of a license could include</span>:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated future product sales;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated royalties we may receive from future product sales;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated contractual milestone payments we may receive;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated expenses we may incur;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Estimated income taxes; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">A discount rate.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We typically estimate the selling price of research and development, or R&amp;D, services by using our internal estimates of the cost to
    perform the specific services. The significant inputs we use to determine the selling price of our R&amp;D services include:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated number of internal hours we will spend performing these services;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work we will perform;</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of work that we will contract with third parties to perform; and</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The estimated cost of API we will use.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For purposes of determining the stand-alone selling price of the R&amp;D services we perform and the API we will deliver, accounting
    guidance requires us to include a markup for a reasonable profit margin.</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">5.</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Recognize revenue</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize revenue in </span>one<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of </span>two<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.</span></div>

<div><br/>
    </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For R&amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based
      on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given
      period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires
      us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Amendments to Agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:</div>

<div><br/>
  </div>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If the goods and/or services are sold at a stand-alone selling price.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement
        and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services
        are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the
        amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative-effect adjustment.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="text-decoration: underline;">Multiple agreements</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:</div>

<div><br/>
  </div>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the agreements were negotiated together with a single objective;</div>
        </td>

  </tr>


</table>

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    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or</div>
        </td>

  </tr>


</table>

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  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Whether the goods and/or services promised under the agreements are a single performance obligation.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative
      Arrangements and Licensing Agreements</span>, for further discussion of our 2018 Strategic Neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"><span style="text-decoration: underline;">Our Revenue Sources</span></span>&#160;</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following are sources of revenue and when we typically recognize revenue.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize royalty revenue, including royalties from
      SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began
    commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As
    a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and
    WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics
    companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In
    the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as
    distributors.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of
    the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
    view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
    distribution fee revenue based on Sobi&#8217;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer
    obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as
    selling, general and administrative, or SG&amp;A, expenses in our consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as
    discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Research and development revenue under collaboration agreements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;D services and manufacturing services.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We provide details about our collaboration agreements in Note 7, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Collaborative Arrangements and Licensing Agreements</span>. For each collaboration, we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Upfront payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation
      is for R&amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;D services.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Milestone payments:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;D services in the transaction price when they
      are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in
      the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when
      we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;D services performance obligation and
      recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone to the
      transaction price.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversely, we recognize in full those milestone payments that we earn based on our partners&#8217; activities when our partner achieves the
    milestone event and we do not have a performance obligation.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">License fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is
      because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"><span style="text-decoration: underline;">Sublicense fees:</span>&#160;</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not
      have any performance obligations related to the sublicense.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Eplontersen Collaboration with AstraZeneca</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the
    U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities
    that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#8217;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca
    related to commercial and medical affairs activities as reductions of our SG&amp;A expense and R&amp;D expense, respectively.</div>
<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReceivablesPolicyTextBlock', window );">Contracts Receivable</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Contracts Receivable</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within one </span><span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a">quarter</span><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> of billing our partner or customer</span>.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022,
    approximately 82.5 percent of our contracts receivables were from one significant customer. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two
    significant customers.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy', window );">Unbilled SPINRAZA Royalties</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unbilled SPINRAZA Royalties</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen
    for SPINRAZA royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueRecognitionPolicyTextBlock', window );">Deferred Revenue</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Deferred Revenue</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.</span> During the years ended December 31, 2022 and 2021, we recognized $73.5 million and $98.1 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostOfSalesPolicyTextBlock', window );">Cost of Sales</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cost of Sales</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpensePolicy', window );">Research, Development and Patent Expenses</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Research, Development and Patent Expenses</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the
    services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in research and development expenses are costs associated with our
    partner agreements. In 2022, 2021 and 2020, patent expenses were $4.7 million, $5.3 million and $4.1 million, respectively.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxPolicyTextBlock', window );">Income Taxes</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Income Taxes</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign
    subsidiaries. </div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerSharePolicyTextBlock', window );">Basic and Diluted Net Loss per Share</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic and Diluted Net Loss per Share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Basic net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We compute basic net loss per share by dividing the total net loss attributable to our common stockholders by our weighted-average number
    of common shares outstanding during the period. For the years ended December 31, 2022 and 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the years ended December 31, 2022 and 2021 was $1.90 and $0.20, respectively.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the year ended December 31, 2020, we calculated total net loss attributable to our common stockholders using our net loss for Ionis on
    a stand-alone basis plus our share of Akcea&#8217;s net loss for the period. To calculate the portion of Akcea&#8217;s net loss attributable to our ownership, we multiplied Akcea&#8217;s net loss per share by the weighted average shares we owned in Akcea. As a result of
    this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share was different than net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of
    operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.45</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111,775</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(197,762</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(246,702</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(444,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3.18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Diluted net loss per share</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent
    shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock underlying the following would have had an anti-dilutive effect on net loss per share:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0.125%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>1%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes;</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dilutive stock options;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested restricted stock units, or RSUs;</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unvested performance restricted stock units, or PRSUs; and</div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Employee Stock Purchase Plan, or ESPP.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">For the years ended December 31, 2022 and 2021, common stock underlying the following would also have had an anti-dilutive effect on net
    loss per share:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> convertible senior notes, or </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes; and</span></div>
        </td>

  </tr>


</table>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 36pt;"/>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#9679;</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Note hedges related to the </span>0%<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> Notes.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Additionally as of December 31, 2022 and 2021, we had warrants related to our 0 percent and 0.125 percent Notes outstanding. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationOptionAndIncentivePlansPolicy', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Stock-Based Compensation Expense</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Stock Options and Stock Purchase Rights:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended
    December 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected
    term based on our historical exercise patterns.</div>

<div><br/>
  </div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">RSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted to our board of directors after June 2020 fully vest after one year.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">PRSU&#8217;s:</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, <span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"><span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"><span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474">one third</span></span></span> of the PRSUs may vest at the end
    of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the
    date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the
    second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the
    date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Refer to Part IV, Item 15, Note 5, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Stockholders&#8217;
      Equity,</span> for additional information regarding our stock-based compensation plans.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy', window );">Noncontrolling Interest in Akcea Therapeutics, Inc.</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Noncontrolling Interest in Akcea Therapeutics, Inc.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Since Akcea&#8217;s IPO in July 2017 and prior to the Akcea Merger
      in October 2020, the shares of Akcea&#8217;s common stock third parties owned represented an interest in Akcea&#8217;s equity that we did not control. During this period our ownership ranged from </span>68 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> to </span>77 percent<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of
      Akcea in our consolidated financial statements. Since Akcea&#8217;s IPO in July 2017 and through the closing of the Akcea Merger, we reflected the noncontrolling interest attributable to other owners of Akcea&#8217;s common stock on a separate line in our
      statements of operations and a separate line within stockholders&#8217; equity in our consolidated balance sheets. In addition, through the closing of the Akcea Merger, we recorded a noncontrolling interest adjustment to account for the stock options Akcea
      granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#8217; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
      compensation expense Akcea had recognized. Additionally, w</span>e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityPolicyTextBlock', window );">Accumulated Other Comprehensive Loss</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Accumulated Other Comprehensive Loss</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):</span></div>

<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,395</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,486</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(417</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(127</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive income (losses) for the year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,812</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,597</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,219</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(57,480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<div>
    <table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; text-align: right;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;</div>
          </td>

  </tr>


</table>
    </div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskCreditRisk', window );">Concentration of Credit Risk</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Concentration of Credit Risk</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#8217;s, Standard &amp; Poor&#8217;s, or S&amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueOfFinancialInstrumentsPolicy', window );">Fair Value Measurements</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value Measurements</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentPolicyTextBlock', window );">Cash, Cash Equivalents and Investments</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Cash, Cash Equivalents and Investments</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#8220;available-for-sale&#8221; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we
      received as part of a technology license or partner agreement. At December 31, 2022, we held equity investments in three publicly traded companies and eight
      privately held companies.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment
    of the same issuer.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryPolicyTextBlock', window );">Inventories</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Inventories</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in
    inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and,
    as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We
    expense these costs as R&amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial
    medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical
    write-offs.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,061</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,699</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,760</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,109</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,033</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentPolicyTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Property, Plant and Equipment</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated Useful</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Lives (in years)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Computer software, laboratory, manufacturing and other equipment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3 to 10</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,351</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,802</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Building, building improvements and building systems</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15 to 40</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">41,158</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144,046</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">-</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,077</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Leasehold improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 15</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,357</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,144</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,575</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">153,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">257,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less accumulated depreciation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(102,653</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,725</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">155,007</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,569</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,294</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,069</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In October 2022, we sold the facilities and related land at our headquarters for net proceeds of $202.6 million in connection with a sale and leaseback transaction.&#160; In connection with the sale of these real estate assets, we de-recognized the related land and improvements,
    building and building improvements, which resulted in a net gain of $150.1 million that we reported in other income (expense) in our consolidated
    statements of operations.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock', window );">Estimated Liability for Clinical Development Costs</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Estimated Liability for Clinical Development Costs</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtPolicyTextBlock', window );">Convertible Debt</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Convertible Debt</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. </span>The<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.</span></div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, we had two
    outstanding convertible senior notes, our 0% Notes, which mature in April 2026, and our 0.125% Notes, which mature in December 2024. Refer to Part IV, Item 15, Note 4, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Long-Term
      Obligations and Commitments</span>, for further details on our convertible senior notes.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DerivativesPolicyTextBlock', window );">Call Spread</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Call Spread</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Derivatives
      and Hedging &#8211; Contracts in Entity&#8217;s Own Equity</span> accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#8217; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify the
    note hedges and warrants in shareholders&#8217; equity at each reporting period.</div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeLeasesPolicyTextBlock', window );">Leases</a></td>
<td class="text">
<div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Leases</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">&#160;</span>We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.</div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingPolicyPolicyTextBlock', window );">Segment Information</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Segment Information</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an
    aggregate basis and manages our operations as a <span style="-sec-ix-hidden:Fact_33bc30118e9548358994c912eadf2161">single</span> operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea&#8217;s operations into ours as of January 1, 2021<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">.</span></div>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock', window );">Recently Adopted Accounting Standards</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Recently Adopted Accounting Standards</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities
    subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity
    securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter
    of 2022. This guidance did not have a material impact on our consolidated financial statements.</div>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We do not expect any other recently issued accounting standards to have a material impact to our financial results.</div>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for estimating the liability for clinical development costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for credit risk.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 825<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126941378&amp;loc=d3e61044-112788<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskCreditRisk</td>
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<tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy regarding (1) the principles it follows in consolidating or combining the separate financial statements, including the principles followed in determining the inclusion or exclusion of subsidiaries or other entities in the consolidated or combined financial statements and (2) its treatment of interests (for example, common stock, a partnership interest or other means of exerting influence) in other entities, for example consolidation or use of the equity or cost methods of accounting. The accounting policy may also address the accounting treatment for intercompany accounts and transactions, noncontrolling interest, and the income statement treatment in consolidation for issuances of stock by a subsidiary.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=d3e5614-111684<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for subsidiaries or other investments that are consolidated, including the accounting treatment for intercompany accounts or transactions and any noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=d3e5614-111684<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for cost of product sold and service rendered.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 705<br> -URI https://asc.fasb.org/topic&amp;trid=2122478<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CostOfSalesPolicyTextBlock</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy related to debt. Includes, but is not limited to, debt issuance costs, the effects of refinancings, method of amortizing debt issuance costs and original issue discount, and classifications of debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtPolicyTextBlock</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for its derivative instruments and hedging activities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41620-113959<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41638-113959<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -URI https://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=SL5579245-113959<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=d3e41675-113959<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(n))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=125515794&amp;loc=SL5579240-113959<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DerivativesPolicyTextBlock</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerSharePolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for computing basic and diluted earnings or loss per share for each class of common stock and participating security. Addresses all significant policy factors, including any antidilutive items that have been excluded from the computation and takes into account stock dividends, splits and reverse splits that occur after the balance sheet date of the latest reporting period but before the issuance of the financial statements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3630-109257<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerSharePolicyTextBlock</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for determining the fair value of financial instruments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 60<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=7493716&amp;loc=d3e21868-110260<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13279-108611<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for income taxes, which may include its accounting policies for recognizing and measuring deferred tax assets and liabilities and related valuation allowances, recognizing investment tax credits, operating loss carryforwards, tax credit carryforwards, and other carryforwards, methodologies for determining its effective income tax rate and the characterization of interest and penalties in the financial statements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 25<br> -URI https://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=d3e32247-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32847-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32840-109319<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL116659661-227067<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -URI https://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=d3e32280-109318<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32809-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxPolicyTextBlock</td>
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<tr>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of inventory accounting policy for inventory classes, including, but not limited to, basis for determining inventory amounts, methods by which amounts are added and removed from inventory classes, loss recognition on impairment of inventories, and situations in which inventories are stated above cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4556-108314<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -URI https://asc.fasb.org/topic&amp;trid=2126998<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 330<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6471895&amp;loc=d3e55923-109411<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 330<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=116847112&amp;loc=d3e4492-108314<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 45<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126900757&amp;loc=d3e543-108305<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6361739&amp;loc=d3e7789-107766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InvestmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for investment in financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(3)(b))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 323<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=114001798&amp;loc=d3e33918-111571<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InvestmentPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeLeasesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for leasing arrangement entered into by lessee.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918666-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeLeasesPolicyTextBlock</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy pertaining to new accounting pronouncements that may impact the entity's financial reporting. Includes, but is not limited to, quantification of the expected or actual impact.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NewAccountingPronouncementsPolicyPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OrganizationConsolidationAndPresentationOfFinancialStatementsAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for long-lived, physical asset used in normal conduct of business and not intended for resale. Includes, but is not limited to, work of art, historical treasure, and similar asset classified as collections.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 958<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126982197&amp;loc=d3e99779-112916<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 958<br> -SubTopic 360<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=126982197&amp;loc=d3e99893-112916<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReceivablesPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for receivable. Includes, but is not limited to, accounts receivable and financing receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=123577603&amp;loc=d3e5033-111524<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10178-111534<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10149-111534<br><br>Reference 4: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=84159169&amp;loc=d3e10133-111534<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReceivablesPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpensePolicy">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for costs it has incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpensePolicy</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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</tr>
<tr>
<td><strong> Data Type:</strong></td>
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</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
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</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue from contract with customer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 17<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130561-203045<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130563-203045<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -URI https://asc.fasb.org/topic&amp;trid=49130388<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130563-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 19<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130564-203045<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130566-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerPolicyTextBlock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:textBlockItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueRecognitionPolicyTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for revenue. Includes revenue from contract with customer and from other sources.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126899994&amp;loc=d3e18823-107790<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueRecognitionPolicyTextBlock</td>
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<tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for segment reporting.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 29<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8864-108599<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for award under share-based payment arrangement. Includes, but is not limited to, methodology and assumption used in measuring cost.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(v)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -URI https://asc.fasb.org/topic&amp;trid=2228938<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 14.D.2.Q6)<br> -URI https://asc.fasb.org/extlink&amp;oid=122041274&amp;loc=d3e301413-122809<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for its capital stock transactions, including dividends and accumulated other comprehensive income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21459-112644<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for treatment of receivables that are billable but have not been billed as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 310<br> -URI https://asc.fasb.org/topic&amp;trid=2196771<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Disclosure of accounting policy for the use of estimates in the preparation of financial statements in conformity with generally accepted accounting principles.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6191-108592<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6161-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6143-108592<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6061-108592<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6132-108592<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e5967-108592<br></p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367636640">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEarningsPerShareBasicByCommonClassTextBlock', window );">Basic Net Loss per Share</a></td>
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<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31, 2020</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Owned in Akcea</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Akcea</span>&#8217;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">s</span></div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Basic Net Loss</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Calculation</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the pre-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">77,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1.45</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111,775</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s net loss in the post-merger period attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(85,987</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Akcea&#8217;s total net loss attributable to our ownership</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(197,762</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ionis&#8217; stand-alone net loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(246,702</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net loss available to Ionis common stockholders</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(444,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average shares outstanding</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net loss per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3.18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock', window );">Changes in Accumulated Other Comprehensive Loss</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):</span></div>

<div style="text-align: justify;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> </span><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(25,290</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unrealized gains (losses) on securities, net of tax (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,395</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,486</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,729</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Currency translation adjustment</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(417</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">617</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(127</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net other comprehensive income (losses) for the year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,812</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,597</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,219</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance accumulated other comprehensive loss</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(57,480</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,668</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(21,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<div>
    <table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; text-align: right;">
            <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</div>
          </td>

    <td style="width: auto; vertical-align: top;">
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;</div>
          </td>

  </tr>


</table>
    </div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfInventoryCurrentTableTextBlock', window );">Inventory</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our inventory consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- clinical</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,061</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,507</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Raw materials- commercial</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,699</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,139</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total raw materials</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19,760</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,646</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Work in process</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,109</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,770</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Finished goods</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">390</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total inventory</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,033</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24,806</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentTextBlock', window );">Property, Plant and Equipment</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,351</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">144,046</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land improvements</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,077</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28,357</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,144</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Furniture and fixtures</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5 to 10</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,575</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,591</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">153,441</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">257,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less accumulated depreciation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(87,716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(102,653</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">65,725</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">155,007</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Land</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,569</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,062</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#160;Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,294</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,069</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfAccruedLiabilitiesTableTextBlock', window );">Accrued Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our accrued liabilities consisted of the following (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630374193008">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments (Tables)<br></strong></div></th>
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<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2022:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">One year</span>
            or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">one year</span>
            but within <span style="text-indent: 0pt;">two years</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">After <span style="text-indent: 0pt;">two years</span>
            but within <span style="text-indent: 0pt;"><span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30">three and a half years</span></span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrealizedGainLossOnInvestmentsTableTextBlock', window );">Summary of Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following is a summary of our investments (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2022</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">513,790</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,365</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">509,448</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">133,585</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,829</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">131,756</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">512,655</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">507,554</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57,484</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,816</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,008</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,223,522</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">64</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(12,018</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,211,568</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">227,631</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(10,143</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">217,502</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,339</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,040</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">33,299</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">245,030</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,109</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">240,921</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">116</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(329</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,101</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">525,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">130</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(15,621</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">509,823</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,748,836</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">194</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27,639</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,721,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">40,372</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">35,012</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,257</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,358</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,911</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,783,848</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,451</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,997</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,772,302</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amortized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gross Unrealized</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"> Cost</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Gains</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Available-for-sale securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">383,870</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(226</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,372</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,493</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">19</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48,494</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,424</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(64</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,360</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,770</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">134,778</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of one year or less</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">612,557</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">792</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(345</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">613,004</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">382,000</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">331</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,644</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">379,687</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,935</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(561</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">72,374</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,635</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">139</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(500</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">137,274</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,909</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(224</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">39,686</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,136</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total securities with a maturity of more than one year</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">638,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">471</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,966</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">635,120</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,172</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,311</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,248,124</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Equity securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in other current assets (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,897</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,145</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities included in deposits and other assets (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,615</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16,707</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,322</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">27,512</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">23,852</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50,527</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total available-for-sale and equity securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,278,684</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25,115</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5,148</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,298,651</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Includes investments classified as cash
            equivalents in our consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $7.7 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized
              non-cash loss in our consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.</span>&#160;</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus
            or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in our consolidated balance
              sheets.</span></div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock', window );">Temporarily Impaired Investments</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">The following is a summary of our investments we considered to be
      temporarily impaired at&#160;</span>December 31, 2022<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">&#160;(in thousands).
      All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more
      likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#8217; amortized cost basis at maturity.</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Less than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">More than 12 Months of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Temporary Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Total Temporary</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Impairment</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number of</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Investments</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Estimated</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Fair Value</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unrealized</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Losses</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">384,136</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,629</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">305,367</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(11,879</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">689,503</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,508</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">93,862</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(538</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">70,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,331</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">164,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2,869</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">616,826</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,082</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,325</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">703,151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">110</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,117</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(225</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31,465</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(790</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49,582</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,015</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,993</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total temporarily impaired securities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,112,941</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(9,474</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">499,383</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,165</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(27,639</div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630379257920">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fair Value Measurements (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueDisclosuresAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following tables present the major security types we held at December 31, 2022 and 2021&#160;<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">that we regularly measure and carry at fair value</span>. As of December 31, 2022, we did not have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy
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<div><br/>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,655</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">211,655</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

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          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">726,950</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">726,950</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,055</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">165,055</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">748,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">748,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,917</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">74,917</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,994</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
          </div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,539</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,943,585</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">970,669</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">972,916</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">December 31, 2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Quoted Prices in</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Active Markets</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 1)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant Other</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Observable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 2)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Significant</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Unobservable Inputs</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Level 3)</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cash equivalents (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">541,199</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Corporate debt securities (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">764,059</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by U.S. government agencies (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,868</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by the U.S. Treasury (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">182,634</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Debt securities issued by states of the U.S. and political subdivisions of the states (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">174,464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other municipal debt securities (2)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,099</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div>
            <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Publicly traded equity securities included in other current assets (4)</div>
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">18,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,875</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,807,528</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">727,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065,490</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,330</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in cash and cash equivalents in our
            consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in short-term investments.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$11.0 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Included in other current assets in our
            consolidated balance sheets.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


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    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$2.3 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</div>
        </td>

  </tr>


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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375574400">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The carrying value of our long-term obligations was as follows (in thousands):</div>

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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0 percent</span>
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">622,242</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">619,119</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">0.125 percent</span>
            convertible senior notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">544,504</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">542,314</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">186,156</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">22,058</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Mortgage debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,998</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">60,054</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,295</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,505</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,369,195</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,251,050</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: current portion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,535</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,526</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total Long-Term Obligations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,361,660</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,247,524</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ContractualObligationFiscalYearMaturityScheduleTableTextBlock', window );">Debt Maturity Schedules</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2022 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2023</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,281</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">550,107</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">595</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2026</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">633,095</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2027</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">447</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">8,708</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total debt and mortgage maturities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,194,233</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion included in other current liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(151</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Fixed and determinable interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,526</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14,831</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,175,725</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseInformationTableTextBlock', window );">Amounts Related to Operating Leases</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Amounts related to our operating leases were as follows (dollar amounts in millions):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">At December 31, 2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use operating lease assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">181.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">186.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average remaining lease term</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13.8 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Weighted average discount rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityMaturityTableTextBlock', window );">Future Payments for Operating Lease Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As of December 31, 2022, the future payments for our operating lease liabilities are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Operating</span> <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;">Leases</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Year ending December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2023</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,071</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2024</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">2025</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,640</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2026</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,781</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2027</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">20,800</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Thereafter</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">196,911</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total minimum lease payments</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">299,594</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%;" valign="bottom">
          <div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Imputed interest</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(113,438</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Less: Current portion (included in <span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32">other current liabilities</span>)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(7,215</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">178,941</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ConvertibleNotesDisclosureLineItems', window );"><strong>Convertible Notes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebtTableTextBlock', window );">Convertible Senior Notes</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
    we had the following 0% Notes outstanding (in millions except interest rate and price per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0% Notes</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">632.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Maturity date</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_ca0956ae2da341f1b584cfebcf6fbda4">April 2026</span></div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.84</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">76.39</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total shares of common stock subject to conversion</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10.9</div>
        </td>

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<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">At December 31, 2022,
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<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: top; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">0.125% Notes</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Outstanding principal balance</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">548.8</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Unamortized debt issuance costs</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="-sec-ix-hidden:Fact_823fe367bb0d42249b87ea8d290aa62a">December 2024</span></div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest rate</div>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: top;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.125 percent</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective interest rate</div>
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.5 percent</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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          <div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Conversion price per share</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective conversion price per share with call spread</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher SEC<br> -Name Regulation S-K (SK)<br> -Number 229<br> -Section 303<br> -Paragraph (a)<br> -Subparagraph (5)<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630374275296">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedCompensationStockOptionsActivityTableTextBlock', window );">Stock Option Activity</a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2022 (in thousands, except per share and contractual life data):</div>

<div><br/>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Average Exercise</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Exercised</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(123</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">29.35</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited/expired</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,860</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.96</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Outstanding at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,970</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">50.57</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.01</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,243</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Exercisable at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,285</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53.74</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.56</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,651</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


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<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfSharebasedCompensationRestrictedStockAndRestrictedStockUnitsActivityTableTextBlock', window );">Restricted Stock Unit Activity</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the RSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2021</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,618</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.05</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,401</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">36.14</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(958</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57.05</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(295</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.61</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,766</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">48.30</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationPerformanceSharesAwardUnvestedActivityTableTextBlock', window );">Performance Restricted Stock Unit Activity</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes the PRSU activity for the year ended December 31, 2022 (in thousands, except per share data):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Number</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">of Shares</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Weighted Average</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Grant Date Fair</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Value Per Share</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2021</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.20</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Granted</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">42.28</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Vested</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(16</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">75.03</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cancelled/forfeited</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="text-indent: 0pt;">Non-vested at December 31, 2022</span></div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">52.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTextBlock', window );">Stock-Based Compensation Expense</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Cost of sales</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">533</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">456</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,991</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Research, development and patent</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">73,704</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">87,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">115,584</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Selling, general and administrative</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">26,027</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">32,700</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">112,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">100,264</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">120,678</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">230,117</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardStockOptionsValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for Stock Options</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Employee Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">58.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6.3 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.9 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4.7 years</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>

<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis Board of Director Stock Options:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
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  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7.4 years</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

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<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfShareBasedPaymentAwardEmployeeStockPurchasePlanValuationAssumptionsTableTextBlock', window );">Weighted-Average Assumptions for ESPP</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;">Ionis ESPP:</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Risk-free interest rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.8</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Dividend yield</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Volatility</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Expected life</div>
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    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6 months</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of allocation of amount expensed and capitalized for award under share-based payment arrangement to statement of income or comprehensive income and statement of financial position. Includes, but is not limited to, corresponding line item in financial statement.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure for stock option plans. Includes, but is not limited to, outstanding awards at beginning and end of year, grants, exercises, forfeitures, and weighted-average grant date fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (e)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(137,222</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">818</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,670</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) before income taxes</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(257,985</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,148</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(134,552</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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<td class="text">
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our income tax expense (benefit) was as follows (in thousands):</div>

<div><br/>
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<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Current:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,522</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(200</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(837</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,129</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(690</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,782</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">339</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">518</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total current income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,463</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Federal</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">341,728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred income tax benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">341,728</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total income tax expense (benefit)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">345,191</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfEffectiveIncomeTaxRateReconciliationTableTextBlock', window );">Reconciliation of Statutory to Effective Tax Rate</a></td>
<td class="text">
<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The
    sources and tax effects of the differences are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


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        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(29,148</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(134,552</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Statutory rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(54,177</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6,121</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(28,256</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">21.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">State income tax net of federal benefit</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13,622</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,278</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(14.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(37,705</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">28.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Foreign</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(49</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">143</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.5</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">49</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net change in valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,951</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(40.7</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2,885</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

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  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(18,774</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred tax true-up</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(20</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(206</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Tax rate change</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,091</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12,838</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(32,951</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">24.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Non-deductible compensation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,085</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(17.4</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,931</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.9</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other non-deductible items</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">57</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.3</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">193</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Stock-based compensation</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">14,030</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5.4</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">4,720</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(16.2</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17,435</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(13.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Impacts from Akcea Merger</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(22,032</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">16.4</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">364</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,503</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,391</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effective rate</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11,737</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(551</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">345,191</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(256.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfDeferredTaxAssetsAndLiabilitiesTableTextBlock', window );">Deferred Tax Assets and Liabilities</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Significant components of our deferred tax assets and liabilities as of December 31, 2022 and 2021 are as follows (in thousands):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Assets:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom">&#160;</td>

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  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,600</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">85,700</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,330</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,983</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">86,611</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Intangible and capital assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">104,649</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">92,542</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Convertible debt</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34,384</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,681</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Interest expense limitation</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,996</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Capitalized research and development expenses</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">119,635</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Long-term lease liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">45,612</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5,119</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">15,813</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">9,929</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total deferred tax assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">858,014</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">706,346</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Deferred Tax Liabilities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Fixed assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,475</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3,303</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Right-of-use assets</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(44,504</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4,159</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Other</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(313</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1,111</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net deferred tax asset</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">808,722</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">697,773</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Valuation allowance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(808,722</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(697,773</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total net deferred tax assets and liabilities</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div><br/>
  </div>
<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ScheduleOfUnrecognizedTaxBenefitsRollForwardTableTextBlock', window );">Gross Unrecognized Tax Benefits</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following table summarizes our gross unrecognized tax benefits <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">(in
      thousands):</span></div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Beginning balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,163</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">69,784</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Decrease for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(267</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(695</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(24,154</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for prior period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">259</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">263</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">7,023</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Increase for current period tax positions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,490</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,354</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,510</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Ending balance of unrecognized tax benefits</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56,567</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">55,085</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">54,163</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the components of income tax expense attributable to continuing operations for each year presented including, but not limited to: current tax expense (benefit), deferred tax expense (benefit), investment tax credits, government grants, the benefits of operating loss carryforwards, tax expense that results from allocating certain tax benefits either directly to contributed capital or to reduce goodwill or other noncurrent intangible assets of an acquired entity, adjustments of a deferred tax liability or asset for enacted changes in tax laws or rates or a change in the tax status of the entity, and adjustments of the beginning-of-the-year balances of a valuation allowance because of a change in circumstances that causes a change in judgment about the realizability of the related deferred tax asset in future years.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the components of net deferred tax asset or liability recognized in an entity's statement of financial position, including the following: the total of all deferred tax liabilities, the total of all deferred tax assets, the total valuation allowance recognized for deferred tax assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32537-109319<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the reconciliation using percentage or dollar amounts of the reported amount of income tax expense attributable to continuing operations for the year to the amount of income tax expense that would result from applying domestic federal statutory tax rates to pretax income from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of income before income tax between domestic and foreign jurisdictions.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of the change in unrecognized tax benefits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 55<br> -Paragraph 217<br> -URI https://asc.fasb.org/extlink&amp;oid=126976462&amp;loc=d3e36027-109320<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366678288">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member]</a></td>
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<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):</div>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">SPINRAZA royalties (commercial revenue)</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">242.3</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">267.8</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">286.6</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

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    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">124.4</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">161.0</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">122.0</div>
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    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Total revenue from our relationship with Biogen</div>
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    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
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          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">366.7</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">428.8</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">408.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">62</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">53</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">56</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">79.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">254.6</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">88.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">13</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">31</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">12</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">0.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">25.5</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.0</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">3</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

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    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">67.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">17.2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">5.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">11</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">2</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">%</div>
        </td>

  </tr>


</table>
<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamPharmaceuticalsIncMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementsAndNonCollaborativeArrangementTransactionsDisclosureLineItems', window );"><strong>Collaborative Arrangements and Licensing Agreements [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SchedulesOfConcentrationOfRiskByRiskFactorTextBlock', window );">Revenue from Collaborative Relationship</a></td>
<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Alnylam (in millions, except percentage amounts):</div>

<div><br/>
    </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">

        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Year Ended December 31,</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2020</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">R&amp;D revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">47.9</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Percentage of total revenue</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
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    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378224320">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Tables)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<td class="text">
<div style="display:none;"><br/></div>
<div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">The following financial information reflects all normal recurring adjustments, which are, in the opinion
    of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2022 and 2021 are as follows (in thousands, except per share data).</div>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31,</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2022</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">2021</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue (1)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">151,890</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">440,006</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses (2)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">359,909</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">219,403</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income (loss) from operations</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(208,019</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">220,603</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income (loss) (3)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(52,430</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">224,613</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Basic net income (loss) per share (4) (5)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: bottom; width: 76%;" valign="bottom">
          <div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Diluted net income (loss) per share (4) (6)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(0.37</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">)</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


</table>

<div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">________________</div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(1)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(2)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $80 million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(3)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(4)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(5)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;">


  <tr>

    <td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">(6)</td>

    <td style="width: auto; vertical-align: top; text-align: justify;">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):</div>
        </td>

  </tr>


</table>

<div><br/>
  </div>

<table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;">


  <tr>

    <td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom">
          <div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Three Months Ended December 31, 2021</div>
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    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

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          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Numerator)</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Shares</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">(Denominator)</div>
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    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Per-Share</div>
          <div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;">Amount</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Net income available to Ionis common stockholders</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
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        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">141,205</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.59</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Effect of dilutive securities:</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon exercise of stock options</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">46</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable upon restricted stock award issuance</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1,065</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our ESPP</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">&#8212;</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">34</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">0 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">777</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">10,936</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">0.125 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">716</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">6,590</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 2px;" valign="bottom">
          <div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Shares issuable related to our <span style="text-indent: 0pt;">1 percent</span> convertible notes</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">105</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">464</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>

  <tr>

    <td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;">Income available to Ionis common stockholders, plus assumed conversions</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">226,210</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">160,340</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

    <td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom">&#160;</td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">$</div>
        </td>

    <td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom">
          <div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;">1.41</div>
        </td>

    <td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom">&#160;</td>

  </tr>


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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Tabular disclosure of quarterly financial data. Includes, but is not limited to, financial information for fiscal quarters, cumulative effect of a change in accounting principle and earnings per share data.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 270<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126900988&amp;loc=d3e1280-108306<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ScheduleOfQuarterlyFinancialInformationTableTextBlock</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366801232">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basis of Presentation (Details) - Akcea [Member]<br></strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">100.00%<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basis of Presentation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">77.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368415104">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Revenue Recognition (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration with AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerAbstract', window );"><strong>Revenue Recognition [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
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<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="nump">55.00%<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
</div></td></tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630369604880">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Contracts Receivable (Details) - Partner<br></strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractReceivablesAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodAfterBillingWhenPaymentIsReceived', window );">Period of time after billing when payment is received</a></td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfSignificantCustomers', window );">Number of significant customers</a></td>
<td class="nump">1<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | One Significant Customer [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="nump">82.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember', window );">Contracts Receivables [Member] | Credit Concentration [Member] | Two Significant Customers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerAssetNetCurrentAbstract', window );"><strong>Contracts Receivable [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">93.80%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of significant customers with which the Company does business.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfSignificantCustomers</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodAfterBillingWhenPaymentIsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The time period between billing a collaboration partner for goods delivered or services performed that are due unconditionally and payment is received from the collaboration partner, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodAfterBillingWhenPaymentIsReceived</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractReceivablesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractReceivablesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerAssetNetCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_AccountsReceivableMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CreditConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CreditConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_OneSignificantCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_OneSignificantCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_MajorCustomersAxis=ions_TwoSignificantCustomersMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_MajorCustomersAxis=ions_TwoSignificantCustomersMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
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<DOCUMENT>
<TYPE>XML
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367342464">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Deferred Revenue (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityAbstract', window );"><strong>Deferred Revenue [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized', window );">Revenue recognized from amounts in beginning deferred revenue balance</a></td>
<td class="nump">$ 73.5<span></span>
</td>
<td class="nump">$ 98.1<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiabilityRevenueRecognized">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized that was previously included in balance of obligation to transfer good or service to customer for which consideration from customer has been received or is due.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiabilityRevenueRecognized</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<DOCUMENT>
<TYPE>XML
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366653360">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Research, Development and Patent Expenses (Details) - USD ($)<br> $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpenseAbstract', window );"><strong>Research, Development and Patent Expenses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PatentExpenses', window );">Patent expenses</a></td>
<td class="nump">$ 4.7<span></span>
</td>
<td class="nump">$ 5.3<span></span>
</td>
<td class="nump">$ 4.1<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PatentExpenses">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Includes charges for amortization and write-downs of capitalized patent costs as well as legal fees for patent litigation and patent defense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PatentExpenses</td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpenseAbstract</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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</div></td></tr>
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</html>
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<DOCUMENT>
<TYPE>XML
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<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366460304">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Basic and Diluted Net Loss per Share (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="1">2 Months Ended</th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="1">10 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2022</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (0.37)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="nump">$ 1.59<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1],[2]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
<td class="num">$ (3.18)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
<td class="num">$ (444,263)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Income (loss) available to Ionis common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 224,612<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (444,464)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Weighted average shares outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">141,205<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember', window );">Ionis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (246,702)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasicAbstract', window );"><strong>Basic Net Income (Loss) per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary', window );">Weighted average shares owned in Akcea (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">77,095<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net loss per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (1.45)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLoss', window );">Net loss</a></td>
<td class="num">$ (85,987)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (111,775)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (197,762)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="12"></td></tr>
<tr><td colspan="12"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.</td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_WeightedAverageNumberOfSharesOwnedInSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares owned in the subsidiary during the reporting period determined by relating the portion of time within a reporting period that shares have been owned to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_WeightedAverageNumberOfSharesOwnedInSubsidiary</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareBasicAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasicAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of profit or loss for the period, net of income taxes, which is attributable to the parent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1448-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 11<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1377-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of [basic] shares or units, after adjustment for contingently issuable shares or units and other shares or units not deemed outstanding, determined by relating the portion of time within a reporting period that common shares or units have been outstanding to the total time in that period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1448-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberOfSharesOutstandingBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementBusinessSegmentsAxis=ions_IonisCoreMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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</div>
</body>
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</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>70
<FILENAME>R34.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367333184">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Stock-Based Compensation Expense (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th">
<div>Dec. 31, 2022 </div>
<div>Period </div>
<div>shares</div>
</th></tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member', window );">Stock Options Granted Prior to January 1, 2022 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">7 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember', window );">Stock Options Granted on January 1, 2022 and Thereafter [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Employees [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Granted Prior to June 2020 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">4 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember', window );">RSUs [Member] | Board of Directors [Member] | Granted After June 2020 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods', window );">Number of performance periods | Period</a></td>
<td class="nump">3<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest', window );">Number of units guaranteed to vest (in shares) | shares</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest', window );">Percentage of units guaranteed to vest</a></td>
<td class="nump">150.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | One-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Two-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember', window );">PRSUs [Member] | Executive Officers [Member] | Three-Year Period [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="nump">33.30%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">3 years<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of separate performance periods under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfPerformancePeriods</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of units guaranteed to vest under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of vesting of award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedPriorToJanuary12022Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_ShareBasedPaymentArrangementOptionsGrantedOnJanuary12022AndThereafterMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=us-gaap_ShareBasedPaymentArrangementEmployeeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=ions_ShareBasedPaymentArrangementBoardOfDirectorMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedPriorToJune2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedPriorToJune2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_GrantedAfterJune2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_GrantedAfterJune2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GranteeStatusAxis=srt_ExecutiveOfficerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheTwoMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheThreeMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>71
<FILENAME>R35.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368397328">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Noncontrolling Interest in Akcea Therapeutics, Inc. (Details) - Akcea [Member]<br></strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
<th class="th"><div>Jun. 30, 2017</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">68.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract', window );"><strong>Noncontrolling Interest in Akcea Therapeutics, Inc. [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MinorityInterestOwnershipPercentageByParent', window );">Percentage ownership</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">77.00%<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_MinorityInterestOwnershipPercentageByParent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The parent entity's interest in net assets of the subsidiary, expressed as a percentage.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_MinorityInterestOwnershipPercentageByParent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOrSaleOfEquityAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_OwnershipAxis=ions_AkceaTherapeuticsIncMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
<SEQUENCE>72
<FILENAME>R36.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<body>
<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366780176">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Accumulated Other Comprehensive Loss (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 771,737<span></span>
</td>
<td class="nump">$ 743,282<span></span>
</td>
<td class="nump">$ 1,577,459<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary', window );">Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(127)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossNetOfTax', window );">Net other comprehensive income (losses) for the year</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(24,812)<span></span>
</td>
<td class="num">(11,597)<span></span>
</td>
<td class="nump">4,219<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">572,887<span></span>
</td>
<td class="nump">771,737<span></span>
</td>
<td class="nump">743,282<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossTax', window );">Income tax expense included in other comprehensive loss</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember', window );">Accumulated Other Comprehensive Loss [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(32,668)<span></span>
</td>
<td class="num">(21,071)<span></span>
</td>
<td class="num">(25,290)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest', window );">Balance</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(57,480)<span></span>
</td>
<td class="num">(32,668)<span></span>
</td>
<td class="num">(21,071)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AccumulatedNetInvestmentGainLossIncludingPortionAttributableToNoncontrollingInterestMember', window );">Unrealized Gains (Losses) on Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive loss before reclassifications, net of tax</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="num">(24,395)<span></span>
</td>
<td class="num">(11,486)<span></span>
</td>
<td class="nump">3,729<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementEquityComponentsAxis=us-gaap_AccumulatedForeignCurrencyAdjustmentIncludingPortionAttributableToNoncontrollingInterestMember', window );">Currency Translation Adjustment [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract', window );"><strong>Accumulated Other Comprehensive Loss [Roll Forward]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax', window );">Other comprehensive loss before reclassifications, net of tax</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">$ (417)<span></span>
</td>
<td class="num">$ (111)<span></span>
</td>
<td class="nump">$ 617<span></span>
</td>
</tr>
<tr><td colspan="4"></td></tr>
<tr><td colspan="4"><table class="outerFootnotes" width="100%"><tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.</td>
</tr></table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_OtherComprehensiveIncomeLossAdjustmentsFromPurchaseOfNoncontrollingInterestOfSubsidiary">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Adjustments to other comprehensive income (loss) from purchase of noncontrolling interest of subsidiary.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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</tr>
<tr>
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<tr>
<td><strong> Period Type:</strong></td>
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</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeLossBeforeReclassificationsNetOfTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax, before reclassification adjustments of other comprehensive income (loss).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124442411-227067<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 17<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32136-110900<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6450520&amp;loc=d3e32583-110901<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14A<br> -URI https://asc.fasb.org/extlink&amp;oid=126968391&amp;loc=SL7669686-108580<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=124507222&amp;loc=d3e1436-108581<br><br>Reference 6: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=124431353&amp;loc=SL124442407-227067<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 830<br> -SubTopic 30<br> -Section 45<br> -Paragraph 20<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=118261656&amp;loc=d3e32211-110900<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after tax and reclassification adjustments of other comprehensive income (loss).</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherComprehensiveIncomeLossNetOfTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherComprehensiveIncomeLossTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of tax expense (benefit) allocated to other comprehensive income (loss).</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTaxAbstract</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of stockholders' equity (deficit), net of receivables from officers, directors, owners, and affiliates of the entity, attributable to both the parent and noncontrolling interests. Amount excludes temporary equity. Alternate caption for the concept is permanent equity.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378161504">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Cash, Cash Equivalents and Investments (Details)<br></strong></div></th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>Company</div>
</th>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract', window );"><strong>Cash, Cash Equivalents and Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20%</a></td>
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<td class="nump">8<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CashCashEquivalentsAndShortTermInvestmentsAbstract</td>
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<td>duration</td>
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<DOCUMENT>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367392736">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Inventory Valuation (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
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<td class="nump">$ 19,760<span></span>
</td>
<td class="nump">$ 18,646<span></span>
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</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryWorkInProcess', window );">Work in process</a></td>
<td class="nump">2,109<span></span>
</td>
<td class="nump">5,770<span></span>
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</tr>
<tr class="ro">
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<td class="nump">164<span></span>
</td>
<td class="nump">390<span></span>
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<tr class="reu">
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<td class="nump">22,033<span></span>
</td>
<td class="nump">24,806<span></span>
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</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember', window );">Clinical [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">17,061<span></span>
</td>
<td class="nump">14,507<span></span>
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</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember', window );">Commercial [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryNetAbstract', window );"><strong>Inventory [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InventoryRawMaterials', window );">Raw materials</a></td>
<td class="nump">$ 2,699<span></span>
</td>
<td class="nump">$ 4,139<span></span>
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</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryFinishedGoods">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of completed merchandise or goods expected to be sold within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryFinishedGoods</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after valuation and LIFO reserves of inventory expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryNetAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryNetAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryRawMaterials">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of raw materials expected to be sold, or consumed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(4))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryRawMaterials</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InventoryWorkInProcess">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before valuation and LIFO reserves of merchandise or goods in the production process expected to be completed within one year or operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(6)(a)(3))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InventoryWorkInProcess</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_ClinicalRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PublicUtilitiesInventoryAxis=ions_CommercialRawMaterialsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630364849120">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Property, Plant and Equipment (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Oct. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment', window );">Less accumulated depreciation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (87,716)<span></span>
</td>
<td class="num">$ (87,716)<span></span>
</td>
<td class="num">$ (102,653)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">74,294<span></span>
</td>
<td class="nump">74,294<span></span>
</td>
<td class="nump">178,069<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NetProceedsFromSaleOfBuildingsAndLand', window );">Net proceeds from sale of real estate assets</a></td>
<td class="nump">$ 202,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SaleAndLeasebackTransactionGainLossNet', window );">Gain on sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,100<span></span>
</td>
<td class="nump">150,135<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember', window );">Property, Plant and Equipment, Excluding Land [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">153,441<span></span>
</td>
<td class="nump">153,441<span></span>
</td>
<td class="nump">257,660<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentNet', window );">Property, plant and equipment, net</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,725<span></span>
</td>
<td class="nump">65,725<span></span>
</td>
<td class="nump">155,007<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">74,351<span></span>
</td>
<td class="nump">$ 74,351<span></span>
</td>
<td class="nump">72,802<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember', window );">Computer Software, Laboratory, Manufacturing and Other Equipment [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">41,158<span></span>
</td>
<td class="nump">$ 41,158<span></span>
</td>
<td class="nump">144,046<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember', window );">Building, Building Improvements and Building Systems [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">40 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember', window );">Land Improvements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">20 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">10,077<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">28,357<span></span>
</td>
<td class="nump">$ 28,357<span></span>
</td>
<td class="nump">20,144<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember', window );">Leasehold Improvements [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">9,575<span></span>
</td>
<td class="nump">$ 9,575<span></span>
</td>
<td class="nump">10,591<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember', window );">Furniture and Fixtures [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentUsefulLife', window );">Estimated useful life</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Land [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentAbstract', window );"><strong>Property, Plant and Equipment [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentGross', window );">Property, plant and equipment</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,569<span></span>
</td>
<td class="nump">$ 8,569<span></span>
</td>
<td class="nump">$ 23,062<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NetProceedsFromSaleOfBuildingsAndLand">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from sale of buildings and held for use in connection with a sale and leaseback transaction, net of the cash outflow to repay the outstanding mortgage debt and pay property taxes and fees.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NetProceedsFromSaleOfBuildingsAndLand</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated depreciation, depletion and amortization for physical assets used in the normal conduct of business to produce goods and services.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(14))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(13))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount after accumulated depreciation, depletion and amortization of physical assets used in the normal conduct of business to produce goods and services and not intended for resale. Examples include, but are not limited to, land, buildings, machinery and equipment, office equipment, and furniture and fixtures.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 360<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6391035&amp;loc=d3e2868-110229<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 360<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429447&amp;loc=SL124453093-239630<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 852<br> -SubTopic 10<br> -Section 55<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=84165509&amp;loc=d3e56426-112766<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentUsefulLife">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Useful life of long lived, physical assets used in the normal conduct of business and not intended for resale, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days. Examples include, but not limited to, land, buildings, machinery and equipment, office equipment, furniture and fixtures, and computer equipment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentUsefulLife</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SaleAndLeasebackTransactionGainLossNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale and leaseback transaction from transfer of asset accounted for as sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 40<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128295416&amp;loc=SL77919786-209982<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SaleAndLeasebackTransactionGainLossNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PropertyPlantAndEquipmentExcludingLandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_EquipmentAndComputerSoftwareMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_BuildingAndBuildingImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LeaseholdImprovementsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_FurnitureAndFixturesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367542320">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Accrued Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrentAbstract', window );"><strong>Accrued Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedClinicalExpenses', window );">Clinical expenses</a></td>
<td class="nump">$ 116,460<span></span>
</td>
<td class="nump">$ 65,730<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedInLicensingFeesCurrent', window );">In-licensing expenses</a></td>
<td class="nump">7,945<span></span>
</td>
<td class="nump">8,044<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AccruedCommercialExpensesCurrent', window );">Commercial expenses</a></td>
<td class="nump">3,498<span></span>
</td>
<td class="nump">2,471<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherAccruedLiabilitiesCurrent', window );">Other miscellaneous expenses</a></td>
<td class="nump">12,198<span></span>
</td>
<td class="nump">12,315<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AccruedLiabilitiesCurrent', window );">Total accrued liabilities</a></td>
<td class="nump">$ 140,101<span></span>
</td>
<td class="nump">$ 88,560<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedClinicalExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for clinical expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedClinicalExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedCommercialExpensesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for commercial expenses. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedCommercialExpensesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AccruedInLicensingFeesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred through that date and payable for in-licensing fees under collaboration agreements. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AccruedInLicensingFeesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Carrying value as of the balance sheet date of obligations incurred and payable, pertaining to costs that are statutory in nature, are incurred on contractual obligations, or accumulate over time and for which invoices have not yet been received or will not be rendered. Examples include taxes, interest, rent and utilities. Used to reflect the current portion of the liabilities (due within one year or within the normal operating cycle if longer).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AccruedLiabilitiesCurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AccruedLiabilitiesCurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherAccruedLiabilitiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expenses incurred but not yet paid classified as other, due within one year or the normal operating cycle, if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherAccruedLiabilitiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
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</DOCUMENT>
<DOCUMENT>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367253904">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Convertible Debt (Details) - Note<br></strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentNumberOfConvertibleNotes', window );">Number of outstanding convertible notes</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentNumberOfConvertibleNotes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of outstanding convertible notes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentNumberOfConvertibleNotes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtByComponentsCurrentAndNoncurrentAlternativeAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378285792">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Call Spread (Details)<br></strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract', window );"><strong>Call Spread [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract', window );"><strong>Call Spread [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GeneralDiscussionOfDerivativeInstrumentsAndHedgingActivitiesAbstract</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366508704">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Organization and Significant Accounting Policies, Segment Information (Details) - Segment<br></strong></div></th>
<th class="th" colspan="2">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract', window );"><strong>Segment Information [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NumberOfOperatingSegments', window );">Number of operating segments</a></td>
<td class="nump">1<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NumberOfOperatingSegments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of operating segments. An operating segment is a component of an enterprise: (a) that engages in business activities from which it may earn revenues and incur expenses (including revenues and expenses relating to transactions with other components of the same enterprise), (b) whose operating results are regularly reviewed by the enterprise's chief operating decision maker to make decisions about resources to be allocated to the segment and assess its performance, and (c) for which discrete financial information is available. An operating segment may engage in business activities for which it has yet to earn revenues, for example, start-up operations may be operating segments before earning revenues.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8672-108599<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NumberOfOperatingSegments</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SegmentReportingDisclosureOfEntitysReportableSegmentsAbstract</td>
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<DOCUMENT>
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378657536">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Investments, Contract Maturity of Available-for-Sale Securities (Details)<br></strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract', window );"><strong>Contract Maturity of Available-for-Sale Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage', window );">One year or less</a></td>
<td class="nump">70.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage', window );">After one year but within two years</a></td>
<td class="nump">28.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage', window );">After two years but within three and a half years</a></td>
<td class="nump">2.00%<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage', window );">Total</a></td>
<td class="nump">100.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage', window );">Percentage of available-for-sale securities with a maturity of less than two years</a></td>
<td class="nump">98.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange1', window );">Maximum contract maturity period, range 1</a></td>
<td class="text">1 year<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange2', window );">Maximum contract maturity period, range 2</a></td>
<td class="text">2 years<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumContractMaturityPeriodRange3', window );">Maximum contract maturity period, range 3</a></td>
<td class="text">3 years 6 months<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond one year but within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage</td>
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<td><strong> Balance Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature beyond two years but within three and one-half years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate percentage of all available-for-sale debt securities, regardless of maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within one year of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of available-for-sale debt securities that mature within two years of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the first range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the second range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumContractMaturityPeriodRange3">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum contract maturity period for the third range of available-for-sale securities, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumContractMaturityPeriodRange3</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366248384">
<tr>
<th class="tl" colspan="2" rowspan="2"><div style="width: 200px;"><strong>Investments, Summary of Investments (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Company</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsAllOtherInvestmentsAbstract', window );"><strong>Ownership Interests in Private and Public Companies [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of privately held companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment', window );">Number of publicly held companies in which there is an equity ownership interest of less than 20% | Company</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">3<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,223,522<span></span>
</td>
<td class="nump">$ 612,557<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">64<span></span>
</td>
<td class="nump">792<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(12,018)<span></span>
</td>
<td class="num">(345)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,211,568<span></span>
</td>
<td class="nump">613,004<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">525,314<span></span>
</td>
<td class="nump">638,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">130<span></span>
</td>
<td class="nump">471<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(15,621)<span></span>
</td>
<td class="num">(3,966)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">509,823<span></span>
</td>
<td class="nump">635,120<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract', window );"><strong>Available-for-sale Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,748,836<span></span>
</td>
<td class="nump">1,251,172<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">194<span></span>
</td>
<td class="nump">1,263<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(27,639)<span></span>
</td>
<td class="num">(4,311)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,721,391<span></span>
</td>
<td class="nump">1,248,124<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">35,012<span></span>
</td>
<td class="nump">27,512<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,257<span></span>
</td>
<td class="nump">23,852<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,358)<span></span>
</td>
<td class="num">(837)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">50,911<span></span>
</td>
<td class="nump">50,527<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,783,848<span></span>
</td>
<td class="nump">1,278,684<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,451<span></span>
</td>
<td class="nump">25,115<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(28,997)<span></span>
</td>
<td class="num">(5,148)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,772,302<span></span>
</td>
<td class="nump">1,298,651<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">513,790<span></span>
</td>
<td class="nump">383,870<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">23<span></span>
</td>
<td class="nump">728<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(4,365)<span></span>
</td>
<td class="num">(226)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">509,448<span></span>
</td>
<td class="nump">384,372<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">227,631<span></span>
</td>
<td class="nump">382,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">14<span></span>
</td>
<td class="nump">331<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(10,143)<span></span>
</td>
<td class="num">(2,644)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">217,502<span></span>
</td>
<td class="nump">379,687<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">133,585<span></span>
</td>
<td class="nump">48,493<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">19<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,829)<span></span>
</td>
<td class="num">(18)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">131,756<span></span>
</td>
<td class="nump">48,494<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">34,339<span></span>
</td>
<td class="nump">72,935<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,040)<span></span>
</td>
<td class="num">(561)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">33,299<span></span>
</td>
<td class="nump">72,374<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">512,655<span></span>
</td>
<td class="nump">45,424<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">23<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(5,124)<span></span>
</td>
<td class="num">(64)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">507,554<span></span>
</td>
<td class="nump">45,360<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">245,030<span></span>
</td>
<td class="nump">137,635<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">139<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(4,109)<span></span>
</td>
<td class="num">(500)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">240,921<span></span>
</td>
<td class="nump">137,274<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">57,484<span></span>
</td>
<td class="nump">134,770<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">18<span></span>
</td>
<td class="nump">45<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(686)<span></span>
</td>
<td class="num">(37)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">56,816<span></span>
</td>
<td class="nump">134,778<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">18,314<span></span>
</td>
<td class="nump">39,909<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">116<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(329)<span></span>
</td>
<td class="num">(224)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">18,101<span></span>
</td>
<td class="nump">39,686<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesCurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of One Year or Less [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">6,008<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(14)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,994<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesNoncurrentAbstract', window );"><strong>Available-for-sale Securities with Maturity of More Than One Year [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,136<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(37)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6,099<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPubliclyTradedCompaniesMember', window );">Publicly Traded Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">11,897<span></span>
</td>
<td class="nump">11,897<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">7,145<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(1,358)<span></span>
</td>
<td class="num">(837)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">10,539<span></span>
</td>
<td class="nump">18,205<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InvestmentsDebtAndEquitySecuritiesAbstract', window );"><strong>Available-for-sale and Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiUnrealizedLoss', window );">Unrealized loss on equity investment</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="num">(7,700)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=ions_EquitySecuritiesPrivateCompaniesMember', window );">Privately Held Equity Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFVNIAbstract', window );"><strong>Equity Securities [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNiCost', window );">Amortized cost</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">23,115<span></span>
</td>
<td class="nump">15,615<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain', window );">Gross unrealized gains</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">17,257<span></span>
</td>
<td class="nump">16,707<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss', window );">Gross unrealized losses</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Estimated fair value</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 40,372<span></span>
</td>
<td class="nump">$ 32,322<span></span>
</td>
</tr>
<tr><td colspan="3"></td></tr>
<tr><td colspan="3"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Includes investments classified as cash
            equivalents in our consolidated balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $7.7 million <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">unrealized
              non-cash loss in our consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.</span>&#160;</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at</span> cost minus impairments, plus
            or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer<span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"> in our consolidated balance
              sheets.</span></td>
</tr>
</table></td></tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxCurrent</td>
</tr>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainBeforeTaxNoncurrent</td>
</tr>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxCurrent</td>
</tr>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossBeforeTaxNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNi</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total of (1) unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale) and (2) unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtSecuritiesAvailableForSaleAndEquitySecuritiesFvNiGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized gain on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedGain</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Accumulated amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EquitySecuritiesFvNiAccumulatedGrossUnrealizedLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of privately-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for under the cost method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of publicly-held companies, in which the entity has an equity ownership interest of less than 20%, with which it conducts business. These are accounted for at fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized gain in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before tax, of unrealized loss in accumulated other comprehensive income (AOCI) on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(12))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26626-111562<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesDebtSecuritiesNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesFairValueToAmortizedCostBasisAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amortized cost of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI https://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
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<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cost of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI). Excludes equity method investment and investment in equity security without readily determinable fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of unrealized loss on investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 321<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126980263&amp;loc=SL75117546-209714<br></p></div>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378295952">
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<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Investments, Investments Temporarily Impaired (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Investment</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 1,112,941<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">499,383<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">1,612,324<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(9,474)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(18,165)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (27,639)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_CorporateDebtSecuritiesMember', window );">Corporate Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">384<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 384,136<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">305,367<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">689,503<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(2,629)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(11,879)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (14,508)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USGovernmentAgenciesDebtSecuritiesMember', window );">Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">48<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 93,862<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">70,233<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">164,095<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(538)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(2,331)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (2,869)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USTreasurySecuritiesMember', window );">Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">75<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 616,826<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">86,325<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">703,151<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(6,082)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(3,151)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (9,233)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_USStatesAndPoliticalSubdivisionsMember', window );">Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">110<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 18,117<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">31,465<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">49,582<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="num">(225)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(790)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (1,015)<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember', window );">Other Municipal Debt Securities [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesAbstract', window );"><strong>Temporarily Impaired Investments [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions', window );">Number of investments | Investment</a></td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract', window );"><strong>Estimated Fair Value [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12Months', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLonger', window );">More than 12 months of temporary impairment</a></td>
<td class="nump">5,993<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPosition', window );">Total temporary impairment</a></td>
<td class="nump">5,993<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract', window );"><strong>Unrealized Losses [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsAccumulatedLoss', window );">Less than 12 months of temporary impairment</a></td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPosition12MonthsOrLongerAccumulatedLoss', window );">More than 12 months of temporary impairment</a></td>
<td class="num">(14)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss', window );">Total temporary impairment</a></td>
<td class="num">$ (14)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionAccumulatedLossAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AvailableForSaleSecuritiesContinuousUnrealizedLossPositionQualitativeDisclosureAbstract">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for more than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for 12 months or longer, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922890-210455<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27337-111563<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of investments in debt securities measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in continuous unrealized loss position for less than 12 months, without an allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position without allowance for credit loss.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27290-111563<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=124269663&amp;loc=SL82922888-210455<br><br>Reference 3: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121590138&amp;loc=SL82922954-210456<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated unrealized loss on investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale), in unrealized loss position, without allowance for credit loss. Includes beneficial interest in securitized financial asset.</p></div>
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<body>
<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630364179248">
<tr>
<th class="tl" colspan="2" rowspan="1"><div style="width: 200px;"><strong>Fair Value Measurements (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2"><div>Dec. 31, 2022</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 1,721,391<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 1,248,124<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 50,911<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 50,527<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 211,655<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">1,943,585<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,807,528<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">10,539<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">18,205<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">726,950<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">11,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">2,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">165,055<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">748,475<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">74,917<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[5]</sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">5,994<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">211,655<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">541,199<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">970,669<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">727,708<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">10,539<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">3,875<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">748,475<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">182,634<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">972,916<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,065,490<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">498,900<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NotesPayableFairValueDisclosure', window );">Fair value of convertible notes</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">587,300<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">726,950<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">764,059<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">165,055<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">120,868<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">74,917<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">174,464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">5,994<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,099<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CashAndCashEquivalentsFairValueDisclosure', window );">Cash equivalents</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AssetsFairValueDisclosure', window );">Total</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="nump">$ 0<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Other Current Assets [Member]</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueNetAssetLiabilityAbstract', window );"><strong>Fair Value Measurements [Abstract]</strong></a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EquitySecuritiesFvNi', window );">Equity securities</a></td>
<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">14,330<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_FairValueByMeasurementFrequencyAxis=us-gaap_FairValueMeasurementsRecurringMember', window );">Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member]</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="th" style="border-bottom: 0px;"><sup></sup></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AvailableForSaleSecuritiesDebtSecurities', window );">Available-for-sale securities</a></td>
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<td class="text">&#160;<span></span>
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<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
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<tr><td colspan="8"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Included in cash and cash equivalents in our
            consolidated balance sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Included in other current assets in our
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</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">$11.0 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top">Included in short-term investments.</td>
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<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">$2.3 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
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</tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of probable future economic benefits obtained or controlled by an entity as a result of past transactions or events.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in debt security measured at fair value with change in fair value recognized in other comprehensive income (available-for-sale).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(6))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 326<br> -SubTopic 30<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124258926&amp;loc=SL82898722-210454<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124260329&amp;loc=d3e26610-111562<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 320<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (aa)<br> -URI https://asc.fasb.org/extlink&amp;oid=126970911&amp;loc=d3e27161-111563<br></p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of currency on hand as well as demand deposits with banks or financial institutions. Includes other kinds of accounts that have the general characteristics of demand deposits. Also includes short-term, highly liquid investments that are both readily convertible to known amounts of cash and so near their maturity that they present insignificant risk of changes in value because of changes in interest rates.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI), classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=124098289&amp;loc=d3e6676-107765<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1A<br> -URI https://asc.fasb.org/extlink&amp;oid=123594786&amp;loc=SL75136599-209740<br></p></div>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_FairValueNetAssetLiabilityAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FairValueNetAssetLiabilityAbstract</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:stringItemType</td>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Fair value portion of notes payable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19,20,22)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NotesPayableFairValueDisclosure</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_FinancialInstrumentAxis=us-gaap_OtherDebtSecuritiesMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td style="white-space:nowrap;">us-gaap_FairValueByFairValueHierarchyLevelAxis=us-gaap_FairValueInputsLevel1Member</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378240048">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Long-Term Obligations (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiability', window );">Lease liabilities</a></td>
<td class="nump">$ 186,156<span></span>
</td>
<td class="nump">$ 22,058<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LoansPayableToBank', window );">Mortgage debt</a></td>
<td class="nump">8,998<span></span>
</td>
<td class="nump">60,054<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OtherLiabilities', window );">Other obligations</a></td>
<td class="nump">7,295<span></span>
</td>
<td class="nump">7,505<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligations', window );">Total</a></td>
<td class="nump">1,369,195<span></span>
</td>
<td class="nump">1,251,050<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsCurrent', window );">Less: current portion</a></td>
<td class="num">(7,535)<span></span>
</td>
<td class="num">(3,526)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LongTermObligationsNoncurrent', window );">Total Long-Term Obligations</a></td>
<td class="nump">1,361,660<span></span>
</td>
<td class="nump">1,247,524<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 622,242<span></span>
</td>
<td class="nump">$ 619,119<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract', window );"><strong>Long-Term Obligations [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleDebt', window );">Convertible senior notes</a></td>
<td class="nump">$ 544,504<span></span>
</td>
<td class="nump">$ 542,314<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, amount of long-term debt, lease obligations and other obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt, lease obligations and other obligations., classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LongTermObligationsNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt, lease obligations and other obligations, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LongTermObligationsNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, carrying amount of debt identified as being convertible into another form of financial instrument (typically the entity's common stock) as of the balance sheet date, which originally required full repayment more than twelve months after issuance or greater than the normal operating cycle of the company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LoansPayableToBank">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Including the current and noncurrent portions, carrying value as of the balance sheet date of loans from a bank with maturities initially due after one year or beyond the normal operating cycle if longer.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16)(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LoansPayableToBank</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
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</tr>
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</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongtermDebtCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongtermDebtCurrentAndNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OtherLiabilities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of liabilities classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03.15)<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OtherLiabilities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630364735168">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Convertible Debt and Call Spread (Details) - USD ($)<br> $ / shares in Units, $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="3">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Nov. 30, 2021</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 61,967<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14,831<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">136,620<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">89,752<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(8,627)<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,373<span></span>
</td>
<td class="nump">4,958<span></span>
</td>
<td class="nump">3,255<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember', window );">Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AmortizationOfFinancingCosts', window );">Amortization of debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,300<span></span>
</td>
<td class="nump">$ 4,900<span></span>
</td>
<td class="nump">$ 3,200<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">632,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 10,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Apr. 30,  2026<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 57.84<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 76.39<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.9<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 46,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">89,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentCarryingAmount', window );">Outstanding principal balance</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 548,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Unamortized debt issuance costs</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 4,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentMaturityDate', window );">Maturity date</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">Dec. 31,  2024<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage', window );">Effective interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.50%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentConvertibleConversionPrice1', window );">Conversion price per share (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 83.28<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread', window );">Effective conversion price per share with call spread (in dollars per share)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 123.38<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion', window );">Total shares of common stock subject to conversion (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CallSpread', window );">Cost of call spread</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 52,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForHedgeFinancingActivities', window );">Purchase of note hedges</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">108,700<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfWarrants', window );">Proceeds from issuance of warrants</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">56,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange', window );">Percentage of principal amount used as purchase price upon occurrence of fundamental change</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedInExchangeFor1PercentNotesMember', window );">0.125% Convertible Senior Notes Issued in Exchange for 1 Percent Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">439,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentIssuedUnderSubscriptionAgreementsMember', window );">0.125% Convertible Senior Notes Issued under Subscription Agreements [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount of offering</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">109,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1% Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract', window );"><strong>Convertible Debt [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentRepurchasedFaceAmount', window );">Principal amount repurchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">247,900<span></span>
</td>
<td class="nump">$ 375,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 247,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfConvertibleDebt', window );">Repurchase of convertible notes</a></td>
<td class="nump">$ 62,000<span></span>
</td>
<td class="nump">$ 257,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainsLossesOnExtinguishmentOfDebt', window );">Loss on early retirement of debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 8,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net cash outflow from payments for hedge transactions and proceeds from the issuance of warrants. The call spread transaction was entered into to minimize the impact of potential economic dilution upon conversion of the 0.125% notes issued.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The computed conversion price per share of the debt instrument based on the the conversion feature embedded in the debt instrument and the impact of the purchased hedges in the call spread transaction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of the principal amount of the notes to be purchased, plus accrued and unpaid interest, upon the occurrence of certain fundamental changes, as set forth in the indenture governing the convertible notes.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DebtInstrumentConvertibleSharesSubjectToConversion">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares of common stock subject to conversion if the debt was converted to equity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DebtInstrumentConvertibleSharesSubjectToConversion</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AmortizationOfFinancingCosts">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of amortization expense attributable to debt issuance costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1F<br> -Subparagraph (b)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495355-112611<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AmortizationOfFinancingCosts</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConvertibleLongtermNotesPayableCurrentAndNoncurrentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentCarryingAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before unamortized (discount) premium and debt issuance costs, of long-term debt. Includes, but is not limited to, notes payable, bonds payable, commercial loans, mortgage loans, convertible debt, subordinated debt and other types of debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6031897-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentCarryingAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentConvertibleConversionPrice1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The price per share of the conversion feature embedded in the debt instrument.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 5<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6031898-161870<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentConvertibleConversionPrice1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of debt instrument at time of issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69C<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495737-112612<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69B<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495735-112612<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateEffectivePercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Effective interest rate for the funds borrowed under the debt agreement considering interest compounding and original issue discount or premium.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6036836-161870<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateEffectivePercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentMaturityDate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Date when the debt instrument is scheduled to be fully repaid, in YYYY-MM-DD format.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 820<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (bbb)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=126976982&amp;loc=d3e19207-110258<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentMaturityDate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:dateItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentRepurchasedFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of the original debt instrument that was repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentRepurchasedFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFinanceCostsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495340-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredFinanceCostsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainsLossesOnExtinguishmentOfDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Difference between the fair value of payments made and the carrying amount of debt which is extinguished prior to maturity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12355-112629<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 50<br> -Section 40<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126972273&amp;loc=d3e12317-112629<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainsLossesOnExtinguishmentOfDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsForHedgeFinancingActivities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for a financial contract that meets the hedge criteria as either cash flow hedge, fair value hedge or hedge of net investment in foreign operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 27<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3581-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsForHedgeFinancingActivities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfWarrants">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from issuance of rights to purchase common shares at predetermined price (usually issued together with corporate debt).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfWarrants</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfConvertibleDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow from the repayment of a long-term debt instrument which can be exchanged for a specified amount of another security, typically the entity's common stock, at the option of the issuer or the holder.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfConvertibleDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
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<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
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<head>
<title></title>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366529936">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Financing Arrangements (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="1">2 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Oct. 31, 2022 </div>
<div>USD ($) </div>
<div>Agreement </div>
<div>Lot</div>
</th>
<th class="th">
<div>Jul. 31, 2017 </div>
<div>USD ($) </div>
<div>Facility</div>
</th>
<th class="th">
<div>Feb. 22, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt', window );">Number of purchased facilities financed with mortgage debt | Facility</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor', window );">Number of purchase and sale agreements entered into with real estate investor | Agreement</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 254,083<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,686<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember', window );">Long-term Mortgage Debt [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentFaceAmount', window );">Face amount</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember', window );">Primary R&amp;D Facility Mortgage [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RepaymentsOfSecuredDebt', window );">Payment of mortgage debt</a></td>
<td class="nump">$ 51,300<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember', window );">Manufacturing Facility Mortgage [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan', window );">Period to make interest only payments on mortgage loan</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember', window );">Primary R&amp;D Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 79,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3.88%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember', window );">Manufacturing Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquireBuildings', window );">Payment to acquire building</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 14,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.20%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember', window );">Headquarters Location in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement', window );">Number of lots of undeveloped land included in purchase and sale agreement | Lot</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="nump">$ 263,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Undeveloped Land in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement', window );">Number of lots of undeveloped land included in purchase and sale agreement | Lot</a></td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember', window );">Undeveloped Land in Carlsbad, California [Member] | Forecast [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract', window );"><strong>Operating Facilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment', window );">Proceeds from sale of real estate assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 33,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of lots of undeveloped land adjacent to the Company's headquarters in Carlsbad, California included in purchase and sale agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of purchase and sale agreements entered into with a real estate investor.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of purchased facilities financed with mortgage debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfPurchasedFacilitiesFinancedWithMortgageDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time to make only payments of interest on the mortgage loan, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodToMakeInterestOnlyPaymentsOnMortgageLoan</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentFaceAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Face (par) amount of debt instrument at time of issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28551-108399<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 55<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=114775985&amp;loc=d3e28878-108400<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=124429444&amp;loc=SL124452920-239629<br><br>Reference 5: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69C<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495737-112612<br><br>Reference 6: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69B<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495735-112612<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentFaceAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentInterestRateStatedPercentage">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentInterestRateStatedPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquireBuildings">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow for acquisition of buildings (properties) whether for investment or use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 13<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3213-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquireBuildings</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PaymentsToAcquirePropertyPlantAndEquipmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of long-lived, physical assets that are used in the normal conduct of business to produce goods and services and not intended for resale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 12<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3179-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromSaleOfPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RepaymentsOfSecuredDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to repay long-term debt that is wholly or partially secured by collateral. Excludes repayments of tax exempt secured debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RepaymentsOfSecuredDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_LongTermMortgageDebtMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_PrimaryResearchAndDevelopmentFacilityMortgageMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DebtInstrumentAxis=ions_ManufacturingFacilityMortgageMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<td><strong> Period Type:</strong></td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_PrimaryResearchAndDevelopmentFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_ManufacturingFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=us-gaap_LandMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_StatementScenarioAxis=srt_ScenarioForecastMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_StatementScenarioAxis=srt_ScenarioForecastMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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</table></div>
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<head>
<title></title>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375716352">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Debt Maturity Schedules (Details)<br> $ in Thousands</strong></div></th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_MaturitiesOfLongTermDebtAbstract', window );"><strong>Debt Maturities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths', window );">2023</a></td>
<td class="nump">$ 1,281<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo', window );">2024</a></td>
<td class="nump">550,107<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree', window );">2025</a></td>
<td class="nump">595<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour', window );">2026</a></td>
<td class="nump">633,095<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive', window );">2027</a></td>
<td class="nump">447<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive', window );">Thereafter</a></td>
<td class="nump">8,708<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebt', window );">Total debt and mortgage maturities</a></td>
<td class="nump">1,194,233<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtCurrent', window );">Less: Current portion included in other current liabilities</a></td>
<td class="num">(151)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_InterestPayableCurrentAndNoncurrent', window );">Less: Fixed and determinable interest</a></td>
<td class="num">(3,526)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFinanceCostsNet', window );">Less: Debt issuance costs</a></td>
<td class="num">(14,831)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LongTermDebtNoncurrent', window );">Total long-term debt</a></td>
<td class="nump">$ 1,175,725<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredFinanceCostsNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after accumulated amortization, of debt issuance costs. Includes, but is not limited to, legal, accounting, underwriting, printing, and registration costs.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495340-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 835<br> -SubTopic 30<br> -Section 45<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124435984&amp;loc=d3e28555-108399<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredFinanceCostsNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_InterestPayableCurrentAndNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of interest payable on debt, including, but not limited to, trade payables.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03.15(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03.15(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_InterestPayableCurrentAndNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebt">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding unamortized premium (discount) and debt issuance cost, of long-term debt. Excludes lease obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (b)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466204&amp;loc=SL6031897-161870<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69C<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495737-112612<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-03(a)(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126734703&amp;loc=d3e572229-122910<br><br>Reference 4: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 55<br> -Paragraph 69B<br> -URI https://asc.fasb.org/extlink&amp;oid=123466577&amp;loc=SL123495735-112612<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 210<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-03(16))<br> -URI https://asc.fasb.org/extlink&amp;oid=126897435&amp;loc=d3e534808-122878<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1D<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495340-112611<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebt</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LongTermDebtCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after unamortized (discount) premium and debt issuance costs, of long-term debt, classified as current. Includes, but not limited to, notes payable, bonds payable, debentures, mortgage loans and commercial paper. Excludes capital lease obligations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.19,20)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing after fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in next fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in fourth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in third fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of long-term debt payable, sinking fund requirement, and other securities issued that are redeemable by holder at fixed or determinable price and date, maturing in second fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1E<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495348-112611<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 3<br> -Subparagraph (SX 210.12-04(a))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24072-122690<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=123465755&amp;loc=d3e1835-112601<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding unamortized premium (discount) and debt issuance cost, of long-term debt classified as noncurrent. Excludes lease obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(22))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366529808">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Operating Leases (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>Lease</div>
</th>
<th class="th">
<div>Jan. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Option </div>
<div>Lot</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 299,594<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseRightOfUseAsset', window );">Right-of-use operating lease assets</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">181,544<span></span>
</td>
<td class="nump">$ 17,974<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="ro">
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 186,156<span></span>
</td>
<td class="nump">22,058<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1', window );">Weighted average remaining lease term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">13 years 9 months 18 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent', window );">Weighted average discount rate</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">6.90%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeasePayments', window );">Operating lease cash payments</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 4,000<span></span>
</td>
<td class="nump">$ 3,300<span></span>
</td>
<td class="nump">$ 3,800<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember', window );">Carlsbad Facility [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpacesMember', window );">Carlsbad Office Spaces [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended', window );">Number of leases that were extended | Lease</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember', window );">Headquarters Location in Carlsbad, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of operating lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">15 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement', window );">Number of lots of undeveloped land included in purchase and sale agreement | Lot</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember', window );">Development Chemistry and Manufacturing Facility in Oceanside, California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of operating lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">20 years 3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember', window );">Boston Office Space [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of operating lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">123 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember', window );">Subleased Office Space in Boston [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LessorOperatingLeaseTermOfContract', window );">Term of sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">83 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LessorOperatingLeasePeriodOfFreeRent', window );">Period of free rent under sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived', window );">Lease payments to be received over term of sublease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 9,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_AnotherOfficeSpaceInBostonMember', window );">Another Office Space in Boston [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeDisclosureAbstract', window );"><strong>Operating Leases [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseTermOfContract', window );">Initial term of operating lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">91 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease', window );">Number of options to extend lease | Option</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseRenewalTerm', window );">Term of lease extension</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">5 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_LesseeOperatingLeasePeriodOfFreeRent', window );">Period of free rent under lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Lease payments to be made over initial term of lease</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 6,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of leases whose term was extended under the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseNumberOfLeasesThatWereExtended</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of options to extend the lease under the lessee's operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeaseNumberOfOptionsToExtendLease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LesseeOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the rent is free under operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LesseeOperatingLeasePeriodOfFreeRent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_LessorOperatingLeasePeriodOfFreeRent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time in which the lessor provides free rent under operating lease to the lessee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LessorOperatingLeasePeriodOfFreeRent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of lots of undeveloped land adjacent to the Company's headquarters in Carlsbad, California included in purchase and sale agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseRenewalTerm">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease renewal, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseRenewalTerm</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessee's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918673-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LessorOperatingLeasePaymentsToBeReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lease payments to be received by lessor for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 30<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=124258985&amp;loc=SL77919396-209981<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LessorOperatingLeasePaymentsToBeReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LessorOperatingLeaseTermOfContract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of lessor's operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 30<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=124258985&amp;loc=SL77919359-209981<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LessorOperatingLeaseTermOfContract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeasePayments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow from operating lease, excluding payments to bring another asset to condition and location necessary for its intended use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 5<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918643-209977<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeasePayments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseRightOfUseAsset">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's right to use underlying asset under operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseRightOfUseAsset</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average discount rate for operating lease calculated at point in time.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageDiscountRatePercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining lease term for operating lease, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (g)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseWeightedAverageRemainingLeaseTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadFacilityMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpacesMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_CarlsbadOfficeSpacesMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_HeadquartersLocationInCarlsbadCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_DevelopmentChemistryAndManufacturingFacilityInOceansideCaliforniaMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_BostonOfficeSpaceMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_SubleasedOfficeSpaceInBostonMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PropertyPlantAndEquipmentByTypeAxis=ions_AnotherOfficeSpaceInBostonMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368323488">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Future Payments for Operating Lease Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract', window );"><strong>Future Payments for Operating Lease Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths', window );">2023</a></td>
<td class="nump">$ 20,071<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo', window );">2024</a></td>
<td class="nump">20,391<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree', window );">2025</a></td>
<td class="nump">20,640<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour', window );">2026</a></td>
<td class="nump">20,781<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive', window );">2027</a></td>
<td class="nump">20,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive', window );">Thereafter</a></td>
<td class="nump">196,911<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue', window );">Total minimum lease payments</a></td>
<td class="nump">299,594<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount', window );">Less: Imputed interest</a></td>
<td class="num">(113,438)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrent', window );">Less: Current portion (included in other current liabilities)</a></td>
<td class="num">(7,215)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityNoncurrent', window );">Total long-term lease liabilities</a></td>
<td class="nump">$ 178,941<span></span>
</td>
<td class="nump">$ 19,432<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList', window );">Operating Lease, Liability, Current, Statement of Financial Position [Extensible Enumeration]</a></td>
<td class="text">Other current liabilities<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLeaseExpense', window );">Rent expense</a></td>
<td class="nump">$ 8,300<span></span>
</td>
<td class="nump">$ 3,400<span></span>
</td>
<td class="nump">$ 3,700<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease due after fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueAfterYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in next fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in fifth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFive</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in fourth fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearFour</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in third fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearThree</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payment for operating lease to be paid in second fiscal year following current fiscal year. Excludes interim and annual periods when interim periods are reported from current statement of financial position date (rolling approach).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityPaymentsDueYearTwo</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of lessee's undiscounted obligation for lease payments in excess of discounted obligation for lease payments for operating lease.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918701-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LesseeOperatingLeaseLiabilityUndiscountedExcessAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of operating lease expense. Excludes sublease income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 4<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918638-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilitiesPaymentsDueAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as current.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Indicates line item in statement of financial position that includes current operating lease liability.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918631-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityCurrentStatementOfFinancialPositionExtensibleList</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>enum2:enumerationSetItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLeaseLiabilityNoncurrent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Present value of lessee's discounted obligation for lease payments from operating lease, classified as noncurrent.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 45<br> -Paragraph 1<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123391704&amp;loc=SL77918627-209977<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLeaseLiabilityNoncurrent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366234784">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Long-Term Obligations and Commitments, Royalty Revenue Monetization (Details) - Subsequent Event [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
</tr>
<tr><th class="th">
<div>Jan. 31, 2023 </div>
<div>USD ($)</div>
</th></tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontRoyaltyPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 500<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones', window );">Maximum amount of payments receivable for additional milestones</a></td>
<td class="nump">625<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">SPINRAZA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="nump">$ 1,500<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">25.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 475<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">45.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="nump">$ 550<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember', window );">Pelacarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyRevenueMonetizationAbstract', window );"><strong>Royalty Revenue Monetization [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid on annual sales of medicine</a></td>
<td class="nump">25.00%<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments receivable for additional milestones under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyRevenueMonetizationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyRevenueMonetizationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontRoyaltyPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontRoyaltyPaymentReceived</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_SpinrazaMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MinimumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_PelacarsenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_PelacarsenMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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</div>
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<SEQUENCE>91
<FILENAME>R55.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378645904">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Preferred and Common Stock (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Common Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized to issue (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">142,057,736<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">142,057,736<span></span>
</td>
<td class="nump">141,210,015<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases</a></td>
<td class="nump">$ 6,373<span></span>
</td>
<td class="nump">$ 11,565<span></span>
</td>
<td class="nump">$ 52,036<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember', window );">Preferred Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Preferred Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesAuthorized', window );">Preferred stock, shares authorized (in shares)</a></td>
<td class="nump">15,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesOutstanding', window );">Preferred stock, shares outstanding (in shares)</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_SeriesCPreferredStockMember', window );">Series C Junior Participating Preferred Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Preferred Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesIssued', window );">Preferred stock, shares issued (in shares)</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PreferredStockSharesOutstanding', window );">Preferred stock, shares outstanding (in shares)</a></td>
<td class="nump">0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StatementClassOfStockAxis=us-gaap_CommonStockMember', window );">Common Stock [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract', window );"><strong>Common Stock [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesAuthorized', window );">Common stock, shares authorized to issue (in shares)</a></td>
<td class="nump">300,000,000<span></span>
</td>
<td class="nump">300,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesIssued', window );">Common stock, shares issued (in shares)</a></td>
<td class="nump">142,100,000<span></span>
</td>
<td class="nump">141,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockSharesOutstanding', window );">Common stock, shares outstanding (in shares)</a></td>
<td class="nump">142,100,000<span></span>
</td>
<td class="nump">141,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance', window );">Common shares reserved for future issuance (in shares)</a></td>
<td class="nump">43,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross', window );">Number of shares issued for stock option exercises, vesting of restricted stock units, and ESPP purchases (in shares)</a></td>
<td class="nump">1,200,000<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="nump">1,700,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions', window );">Net proceeds from stock option exercises, vesting of restricted stock units, and ESPP purchases</a></td>
<td class="nump">$ 6,400<span></span>
</td>
<td class="nump">$ 11,600<span></span>
</td>
<td class="nump">$ 52,000<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate number of common shares reserved for future issuance.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.29)<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockCapitalSharesReservedForFutureIssuance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockNumberOfSharesParValueAndOtherDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
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<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of common shares permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of common shares of an entity that have been sold or granted to shareholders (includes common shares that were issued, repurchased and remain in the treasury). These shares represent capital invested by the firm's shareholders and owners, and may be all or only a portion of the number of shares authorized. Shares issued include shares outstanding and shares held in the treasury.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CommonStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares of common stock outstanding. Common stock represent the ownership interest in a corporation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CommonStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockNumberOfSharesParValueAndOtherDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum number of nonredeemable preferred shares (or preferred stock redeemable solely at the option of the issuer) permitted to be issued by an entity's charter and bylaws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total number of nonredeemable preferred shares (or preferred stock redeemable solely at the option of the issuer) issued to shareholders (includes related preferred shares that were issued, repurchased, and remain in the treasury). May be all or portion of the number of preferred shares authorized. Excludes preferred shares that are classified as debt.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 13<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=SL123496158-112644<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PreferredStockSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Aggregate share number for all nonredeemable preferred stock (or preferred stock redeemable solely at the option of the issuer) held by stockholders. Does not include preferred shares that have been repurchased.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PreferredStockSharesOutstanding</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from issuance of shares under share-based payment arrangement. Includes, but is not limited to, option exercised.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfSharesUnderIncentiveAndShareBasedCompensationPlansIncludingStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number, before forfeiture, of shares issued under share-based payment arrangement. Excludes employee stock ownership plan (ESOP).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensationGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_PreferredStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StatementClassOfStockAxis=us-gaap_SeriesCPreferredStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StatementClassOfStockAxis=us-gaap_SeriesCPreferredStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366695488">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Share Repurchase Program (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Mar. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
<th class="th"><div>Sep. 30, 2019</div></th>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ClassOfStockDisclosuresAbstract', window );"><strong>Share Repurchase Program [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockRepurchaseProgramAuthorizedAmount1', window );">Authorized amount of share repurchase program</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 125,000<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockRepurchasedDuringPeriodShares', window );">Shares repurchased (in shares)</a></td>
<td class="nump">1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">535,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PaymentsForRepurchaseOfCommonStock', window );">Shares repurchased</a></td>
<td class="nump">$ 90,500<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 90,548<span></span>
</td>
<td class="nump">$ 34,400<span></span>
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<td class="text">&#160;<span></span>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ClassOfStockDisclosuresAbstract</td>
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<td>xbrli:stringItemType</td>
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<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash outflow to reacquire common stock during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3291-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td><strong> Data Type:</strong></td>
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<td><strong> Balance Type:</strong></td>
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<td>duration</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of stock repurchase plan authorized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares that have been repurchased during the period and have not been retired and are not held in treasury. Some state laws may govern the circumstances under which an entity may acquire its own stock and prescribe the accounting treatment therefore. This element is used when state law does not recognize treasury stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630362916096">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock Plans (Details)<br></strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jun. 30, 2009 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>Officer </div>
<div>$ / shares </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2021 </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2020 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2019 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2017 </div>
<div>shares</div>
</th>
<th class="th">
<div>Jun. 30, 2015 </div>
<div>shares</div>
</th>
<th class="th">
<div>May 31, 2015 </div>
<div>shares</div>
</th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">14,970,000<span></span>
</td>
<td class="nump">14,089,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,285,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">12,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member', window );">1989 Stock Option Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">29,700,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">23,000,000<span></span>
</td>
<td class="nump">16,000,000<span></span>
</td>
<td class="nump">11,000,000<span></span>
</td>
<td class="nump">5,500,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward', window );">Reduction in fungible share reserve for each share issued pursuant to full value award (n shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">(1.7)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward', window );">Increase in fungible share reserve for each share returning from a full value award (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.7<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">13,700,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">9,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Number of executive officers terminated before change in control when vesting will accelerate for executive officers | Officer</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period before change in control when vesting will accelerate for executive officers</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">3 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers', window );">Period after change in control when vesting will accelerate for executive officers</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">12 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member', window );">2011 Equity Incentive Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,700,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,600,000<span></span>
</td>
<td class="nump">2,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">61,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">7 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Stock Options [Member] | One Year from Date of Grant [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage', window );">Vesting percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1', window );">Period before options are exercisable</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">1 year<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member', window );">2020 Equity Incentive Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1', window );">Vesting period</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">4 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,000,000<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Number of options outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Number of options exercisable (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant', window );">Number of shares available for grant (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member] | Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member', window );">2002 Non-Employee Directors' Stock Option Plan [Member] | Restricted Stock Units [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber', window );">Number of awards outstanding (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_PlanNameAxis=ions_EmployeeStockPurchasePlanMember', window );">Employee Stock Purchase Plan [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract', window );"><strong>Stock Plans [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized', window );">Number of shares authorized for issuance under the Plan (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized', window );">Number of additional shares reserved for issuance (in shares)</a></td>
<td class="nump">150,000<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate', window );">Maximum percentage of employee compensation used to purchase shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent', window );">Percentage of fair market value used to determine purchase price of stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">85.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod', window );">Holding period for purchased stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans', window );">Shares purchased and issued under ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased', window );">Weighted average purchase price (in dollars per share) | $ / shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 28.57<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EmployeeStockPurchasePlanSharesAvailableForPurchase', window );">Shares available for purchase under ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EmployeeStockPurchasePlanSharesAvailableForPurchase">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares available for purchase under an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EmployeeStockPurchasePlanSharesAvailableForPurchase</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average sales price of shares purchased through an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EmployeeStockPurchasePlanWeightedAverageSalesPriceOfSharesPurchased</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Increase (decrease) in the number of shares in the "fungible" share reserve for each share issued pursuant to full value award.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInFungibleShareReserveForEachShareIssuedPursuantToFullValueAward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Increase (decrease) in the number of shares in the "fungible" share reserve for each share of common stock returning from a full value award.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncreaseDecreaseInFungibleShareReserveForEachShareReturningFromFullValueAward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of executive officers terminated by the Company during the period that begins three months before and ends twelve months following a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfExecutiveOfficersTerminatedBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time after a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodAfterChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period of time before a change in control of the Company when vesting will accelerate for options and RSUs outstanding as of the termination date for executive officers, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PeriodBeforeChangeInControlWhenVestingWillAccelerateForExecutiveOfficers</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the holding period from the date of purchase for stock purchased under the plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardHoldingPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedArrangementsToObtainGoodsAndServicesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Estimated period over which an employee is required to provide service in exchange for the equity-based payment award, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period over which grantee's right to exercise award under share-based payment arrangement is no longer contingent on satisfaction of service or performance condition, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days. Includes, but is not limited to, combination of market, performance or service condition.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The highest percentage of annual salary that an employee is permitted to utilize with respect to the plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of equity instruments other than options outstanding, including both vested and non-vested instruments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of additional shares authorized for issuance under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares authorized for issuance under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The difference between the maximum number of shares (or other type of equity) authorized for issuance under the plan (including the effects of amendments and adjustments), and the sum of: 1) the number of shares (or other type of equity) already issued upon exercise of options or other equity-based awards under the plan; and 2) shares (or other type of equity) reserved for issuance on granting of outstanding awards, net of cancellations and forfeitures, if applicable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares into which fully or partially vested stock options outstanding as of the balance sheet date can be currently converted under the option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of options outstanding, including both vested and non-vested options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of vesting of award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardAwardVestingRightsPercentage</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Purchase price of common stock expressed as a percentage of its fair value.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of shares issued during the period as a result of an employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_StockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_StockOptionPlan1989Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_VestingAxis=us-gaap_ShareBasedCompensationAwardTrancheOneMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_IssuedAfterDecember312021Member</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td>na</td>
</tr>
<tr>
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<td></td>
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<tr>
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<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td>na</td>
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<tr>
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<td></td>
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<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member</td>
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<td></td>
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<td>na</td>
</tr>
<tr>
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<td></td>
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<tr>
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<td></td>
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</table></div>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_NonemployeeDirectorsStockOptionPlan2002Member</td>
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<td></td>
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<td>na</td>
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<tr>
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<td></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EmployeeStockPurchasePlanMember</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375569712">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock Option Activity (Details) - Stock Options [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at beginning of period (in shares)</a></td>
<td class="nump">14,089<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross', window );">Granted (in shares)</a></td>
<td class="nump">2,864<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised', window );">Exercised (in shares)</a></td>
<td class="num">(123)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod', window );">Cancelled/forfeited/expired (in shares)</a></td>
<td class="num">(1,860)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber', window );">Outstanding at end of period (in shares)</a></td>
<td class="nump">14,970<span></span>
</td>
<td class="nump">14,089<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber', window );">Exercisable at end of period (in shares)</a></td>
<td class="nump">10,285<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward', window );"><strong>Weighted Average Exercise Price Per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 54.04<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice', window );">Granted (in dollars per share)</a></td>
<td class="nump">34.78<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice', window );">Exercised (in dollars per share)</a></td>
<td class="nump">29.35<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice', window );">Cancelled/forfeited/expired (in dollars per share)</a></td>
<td class="nump">53.96<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice', window );">Outstanding at end of period (in dollars per share)</a></td>
<td class="nump">50.57<span></span>
</td>
<td class="nump">$ 54.04<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice', window );">Exercisable at end of period (in dollars per share)</a></td>
<td class="nump">$ 53.74<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract', window );"><strong>Average Remaining Contractual Term, Aggregate Intrinsic Value and Other [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2', window );">Average remaining contractual term, outstanding at end of period</a></td>
<td class="text">4 years 3 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1', window );">Average remaining contractual term, exercisable at end of period</a></td>
<td class="text">2 years 6 months 21 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue', window );">Aggregate intrinsic value, outstanding at end of period</a></td>
<td class="nump">$ 12,243<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1', window );">Aggregate intrinsic value, exercisable at end of period</a></td>
<td class="nump">$ 1,651<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Weighted average fair value of options granted (in dollars per share)</a></td>
<td class="nump">$ 18.66<span></span>
</td>
<td class="nump">$ 24.35<span></span>
</td>
<td class="nump">$ 29.43<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue', window );">Intrinsic value of options exercised</a></td>
<td class="nump">$ 1,400<span></span>
</td>
<td class="nump">$ 2,500<span></span>
</td>
<td class="nump">$ 15,500<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromStockOptionsExercised', window );">Cash received from exercise of stock options</a></td>
<td class="nump">$ 3,600<span></span>
</td>
<td class="nump">$ 8,500<span></span>
</td>
<td class="nump">$ 43,700<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue', window );">Weighted-average fair value of options exercised (in dollars per share)</a></td>
<td class="nump">$ 40.71<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions', window );">Unrecognized compensation cost related to non-vested stock options</a></td>
<td class="nump">$ 41,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 1 month 6 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average grant-date fair value of options exercised during the reporting period as calculated by applying the disclosed option pricing methodology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for option under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromStockOptionsExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash inflow from exercise of option under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=SL79508275-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromStockOptionsExercised</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of shares into which fully or partially vested stock options outstanding as of the balance sheet date can be currently converted under the option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted-average price as of the balance sheet date at which grantees can acquire the shares reserved for issuance on vested portions of options outstanding and currently exercisable under the stock option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of accumulated difference between fair value of underlying shares on dates of exercise and exercise price on options exercised (or share units converted) into shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For presentations that combine terminations, the number of shares under options that were cancelled during the reporting period as a result of occurrence of a terminating event specified in contractual agreements pertaining to the stock option plan or that expired.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Gross number of share options (or share units) granted during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average grant-date fair value of options granted during the reporting period as calculated by applying the disclosed option pricing methodology.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (d)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount by which the current fair value of the underlying stock exceeds the exercise price of options outstanding.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of options outstanding, including both vested and non-vested options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which grantees can acquire the shares reserved for issuance under the stock option plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which option holders acquired shares when converting their stock options into shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average price at which grantees could have acquired the underlying shares with respect to stock options that were terminated.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(03)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average per share amount at which grantees can acquire shares of common stock by exercise of options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of difference between fair value of the underlying shares reserved for issuance and exercise price of vested portions of options outstanding and currently exercisable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining contractual term for vested portions of options outstanding and currently exercisable or convertible, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average remaining contractual term for option awards outstanding, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (e)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of share options (or share units) exercised during the current period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(1)(iv)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_StockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_StockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366098800">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Restricted Stock Unit Activity (Details) - Restricted Stock Units [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">2,618<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">1,401<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod', window );">Vested (in shares)</a></td>
<td class="num">(958)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod', window );">Cancelled/forfeited (in shares)</a></td>
<td class="num">(295)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at end of period (in shares)</a></td>
<td class="nump">2,766<span></span>
</td>
<td class="nump">2,618<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward', window );"><strong>Weighted Average Grant Date Fair Value per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 58.05<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Granted (in dollars per share)</a></td>
<td class="nump">36.14<span></span>
</td>
<td class="nump">$ 57.02<span></span>
</td>
<td class="nump">$ 60.57<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue', window );">Vested (in dollars per share)</a></td>
<td class="nump">57.05<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue', window );">Cancelled/forfeited (in dollars per share)</a></td>
<td class="nump">48.61<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at end of period (in dollars per share)</a></td>
<td class="nump">$ 48.3<span></span>
</td>
<td class="nump">$ 58.05<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 45.8<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">1 year 2 months 12 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that were forfeited during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average fair value as of the grant date of equity-based award plans other than stock (unit) option plans that were not exercised or put into effect as a result of the occurrence of a terminating event.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of grants made during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value at grant date for nonvested equity-based awards issued during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of non-vested equity-based payment instruments, excluding stock (or unit) options, that validly exist and are outstanding as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Per share or unit weighted-average fair value of nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that vested during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value as of grant date pertaining to an equity-based award plan other than a stock (or unit) option plan for which the grantee gained the right during the reporting period, by satisfying service and performance requirements, to receive or retain shares or units, other instruments, or cash in accordance with the terms of the arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_RestrictedStockUnitsRSUMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
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<head>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366017264">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Performance Restricted Stock Unit Activity (Details) - Performance Restricted Stock Units [Member] - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Millions</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward', window );"><strong>Number of Shares [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at beginning of period (in shares)</a></td>
<td class="nump">59<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod', window );">Granted (in shares)</a></td>
<td class="nump">105<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod', window );">Vested (in shares)</a></td>
<td class="num">(16)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod', window );">Cancelled/forfeited (in shares)</a></td>
<td class="num">(5)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber', window );">Non-vested at end of period (in shares)</a></td>
<td class="nump">143<span></span>
</td>
<td class="nump">59<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward', window );"><strong>Weighted Average Grant Date Fair Value per Share [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at beginning of period (in dollars per share)</a></td>
<td class="nump">$ 79.2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue', window );">Granted (in dollars per share)</a></td>
<td class="nump">42.28<span></span>
</td>
<td class="nump">$ 77.17<span></span>
</td>
<td class="nump">$ 93.09<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue', window );">Vested (in dollars per share)</a></td>
<td class="nump">75.03<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue', window );">Cancelled/forfeited (in dollars per share)</a></td>
<td class="nump">79.11<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue', window );">Non-vested at end of period (in dollars per share)</a></td>
<td class="nump">$ 52.59<span></span>
</td>
<td class="nump">$ 79.2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract', window );"><strong>Unrecognized Compensation Expense [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="nump">$ 2.4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1', window );">Weighted average period for recognition</a></td>
<td class="text">10 months 24 days<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted-average period over which cost not yet recognized is expected to be recognized for award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that were forfeited during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Weighted average fair value as of the grant date of equity-based award plans other than stock (unit) option plans that were not exercised or put into effect as a result of the occurrence of a terminating event.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(03)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of grants made during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value at grant date for nonvested equity-based awards issued during the period on other than stock (or unit) option plans (for example, phantom stock or unit plan, stock or unit appreciation rights plan, performance target plan).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(01)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of non-vested equity-based payment instruments, excluding stock (or unit) options, that validly exist and are outstanding as of the balance sheet date.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Per share or unit weighted-average fair value of nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of equity-based payment instruments, excluding stock (or unit) options, that vested during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The weighted average fair value as of grant date pertaining to an equity-based award plan other than a stock (or unit) option plan for which the grantee gained the right during the reporting period, by satisfying service and performance requirements, to receive or retain shares or units, other instruments, or cash in accordance with the terms of the arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)(2)(iii)(02)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
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<td>na</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_PerformanceSharesMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366236560">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock-based Compensation Expense (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
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<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Oct. 31, 2020</div></th>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 100,264<span></span>
</td>
<td class="nump">$ 120,678<span></span>
</td>
<td class="nump">$ 230,117<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_CostOfSalesMember', window );">Cost of Sales [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">533<span></span>
</td>
<td class="nump">456<span></span>
</td>
<td class="nump">1,991<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=ions_ResearchDevelopmentAndPatentMember', window );">Research, Development and Patent [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">73,704<span></span>
</td>
<td class="nump">87,522<span></span>
</td>
<td class="nump">115,584<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeStatementLocationAxis=us-gaap_SellingGeneralAndAdministrativeExpensesMember', window );">Selling, General and Administrative [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AllocatedShareBasedCompensationExpense', window );">Stock-based compensation expense</a></td>
<td class="nump">$ 26,027<span></span>
</td>
<td class="nump">$ 32,700<span></span>
</td>
<td class="nump">$ 112,542<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ConsolidatedEntitiesAxis=ions_AkceaTherapeuticsIncMember', window );">Akcea [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationAbstract', window );"><strong>Stock-Based Compensation [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions', window );">Unrecognized compensation cost related to non-vested units</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="nump">$ 59,300<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AllocatedShareBasedCompensationExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for award under share-based payment arrangement. Excludes amount capitalized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (h)(1)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AllocatedShareBasedCompensationExpense</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost to be recognized for nonvested award under share-based payment arrangement. Excludes share and unit options.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:monetaryItemType</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368267104">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Stockholders' Equity, Stock-based Valuation Information (Details)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.10%<span></span>
</td>
<td class="nump">0.60%<span></span>
</td>
<td class="nump">1.50%<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">54.50%<span></span>
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<td class="nump">54.00%<span></span>
</td>
<td class="nump">58.60%<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
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<td class="text">4 years 10 months 24 days<span></span>
</td>
<td class="text">4 years 8 months 12 days<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2011 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2011 Equity Incentive Plan [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2020 Equity Incentive Plan [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Employee Stock Options [Member] | 2020 Equity Incentive Plan [Member] | Issued after December 31, 2021 [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod', window );">Award term</a></td>
<td class="text">10 years<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember', window );">Board of Director Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">2.90%<span></span>
</td>
<td class="nump">1.20%<span></span>
</td>
<td class="nump">0.50%<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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<td class="nump">0.00%<span></span>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">56.20%<span></span>
</td>
<td class="nump">55.90%<span></span>
</td>
<td class="nump">57.60%<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">7 years 4 months 24 days<span></span>
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<td class="text">7 years 3 months 18 days<span></span>
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<td class="text">6 years 8 months 12 days<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember', window );">ESPP [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract', window );"><strong>Weighted-Average Assumptions [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate', window );">Risk-free interest rate</a></td>
<td class="nump">1.20%<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
<td class="nump">0.80%<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate', window );">Dividend yield</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
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</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate', window );">Volatility</a></td>
<td class="nump">50.10%<span></span>
</td>
<td class="nump">42.40%<span></span>
</td>
<td class="nump">47.90%<span></span>
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</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1', window );">Expected life</a></td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
<td class="text">6 months<span></span>
</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract</td>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The estimated dividend rate (a percentage of the share price) to be paid (expected dividends) to holders of the underlying shares over the option's term.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The risk-free interest rate assumption that is used in valuing an option on its own shares.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(iv)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Rate of weighted-average expected volatility for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(ii)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsWeightedAverageVolatilityRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period from grant date that an equity-based award expires, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Expected term of award under share-based payment arrangement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (f)(2)(i)<br> -URI https://asc.fasb.org/extlink&amp;oid=128089324&amp;loc=d3e5070-113901<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2011Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardDateAxis=ions_IssuedAfterDecember312021Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardDateAxis=ions_IssuedAfterDecember312021Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_PlanNameAxis=ions_EquityIncentivePlan2020Member</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=ions_BoardOfDirectorStockOptionMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_AwardTypeAxis=us-gaap_EmployeeStockMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378358288">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Income (Loss) Before Income Taxes (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxDisclosureAbstract', window );"><strong>Income Taxes [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic', window );">United States</a></td>
<td class="num">$ (258,493)<span></span>
</td>
<td class="num">$ (29,966)<span></span>
</td>
<td class="num">$ (137,222)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign', window );">Foreign</a></td>
<td class="nump">508<span></span>
</td>
<td class="nump">818<span></span>
</td>
<td class="nump">2,670<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Loss before income tax benefit (expense)</a></td>
<td class="num">$ (257,985)<span></span>
</td>
<td class="num">$ (29,148)<span></span>
</td>
<td class="num">$ (134,552)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of earnings or loss from continuing operations before income taxes that is attributable to domestic operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 940<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126941158&amp;loc=d3e41242-110953<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The portion of earnings or loss from continuing operations before income taxes that is attributable to foreign operations, which is defined as Income or Loss generated from operations located outside the entity's country of domicile.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.3)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxDisclosureAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxDisclosureAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366434272">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Income Tax Expense (Benefit) (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract', window );"><strong>Current [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentFederalTaxExpenseBenefit', window );">Federal</a></td>
<td class="nump">$ 10,522<span></span>
</td>
<td class="num">$ (200)<span></span>
</td>
<td class="num">$ (837)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentStateAndLocalTaxExpenseBenefit', window );">State</a></td>
<td class="nump">1,129<span></span>
</td>
<td class="num">(690)<span></span>
</td>
<td class="nump">3,782<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentForeignTaxExpenseBenefit', window );">Foreign</a></td>
<td class="nump">86<span></span>
</td>
<td class="nump">339<span></span>
</td>
<td class="nump">518<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CurrentIncomeTaxExpenseBenefit', window );">Total current income tax expense (benefit)</a></td>
<td class="nump">11,737<span></span>
</td>
<td class="num">(551)<span></span>
</td>
<td class="nump">3,463<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract', window );"><strong>Deferred [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredFederalIncomeTaxExpenseBenefit', window );">Federal</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">341,728<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit', window );">State</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredIncomeTaxExpenseBenefit', window );">Total deferred income tax benefit</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="nump">341,728<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="nump">$ 11,737<span></span>
</td>
<td class="num">$ (551)<span></span>
</td>
<td class="nump">$ 345,191<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentFederalTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current federal tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, current national tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentFederalTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentForeignTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current foreign income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentForeignTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) pertaining to taxable income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentIncomeTaxExpenseBenefit</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentIncomeTaxExpenseBenefitContinuingOperationsAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_CurrentStateAndLocalTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current state and local tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, current regional, territorial, and provincial tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_CurrentStateAndLocalTaxExpenseBenefit</td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred federal tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, deferred national tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td style="white-space:nowrap;">us-gaap_DeferredFederalIncomeTaxExpenseBenefit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred income tax expense (benefit) pertaining to income (loss) from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.1)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.2)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3602-108585<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefit</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredIncomeTaxExpenseBenefitContinuingOperationsAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred state and local tax expense (benefit) attributable to income (loss) from continuing operations. Includes, but is not limited to, deferred regional, territorial, and provincial tax expense (benefit) for non-US (United States of America) jurisdiction.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32639-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(1)(Note 1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredStateAndLocalIncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<td><strong> Period Type:</strong></td>
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</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
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<td>xbrli:monetaryItemType</td>
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<td>duration</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367564176">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract', window );"><strong>Reconciliation Between Effective and Statutory Tax Rate [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest', window );">Pre-tax income (loss)</a></td>
<td class="num">$ (257,985)<span></span>
</td>
<td class="num">$ (29,148)<span></span>
</td>
<td class="num">$ (134,552)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate', window );">Statutory rate</a></td>
<td class="num">(54,177)<span></span>
</td>
<td class="num">(6,121)<span></span>
</td>
<td class="num">(28,256)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="num">(13,622)<span></span>
</td>
<td class="nump">4,278<span></span>
</td>
<td class="num">(37,705)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="num">(49)<span></span>
</td>
<td class="nump">143<span></span>
</td>
<td class="nump">49<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="nump">104,951<span></span>
</td>
<td class="nump">2,885<span></span>
</td>
<td class="nump">460,898<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount', window );">Loss on debt transactions</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">262<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="num">(39,729)<span></span>
</td>
<td class="num">(23,198)<span></span>
</td>
<td class="num">(18,774)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes', window );">Deferred tax true-up</a></td>
<td class="num">(20)<span></span>
</td>
<td class="num">(24)<span></span>
</td>
<td class="num">(206)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="num">(3,091)<span></span>
</td>
<td class="nump">12,838<span></span>
</td>
<td class="num">(32,951)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount', window );">Non-deductible compensation</a></td>
<td class="nump">3,023<span></span>
</td>
<td class="nump">5,085<span></span>
</td>
<td class="nump">7,931<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther', window );">Other non-deductible items</a></td>
<td class="nump">57<span></span>
</td>
<td class="nump">84<span></span>
</td>
<td class="nump">193<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">14,030<span></span>
</td>
<td class="nump">4,720<span></span>
</td>
<td class="nump">17,435<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount', window );">Impacts from Akcea Merger</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">0<span></span>
</td>
<td class="num">(22,032)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxReconciliationOtherAdjustments', window );">Other</a></td>
<td class="nump">364<span></span>
</td>
<td class="num">(1,503)<span></span>
</td>
<td class="num">(1,391)<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxExpenseBenefit', window );">Total income tax expense (benefit)</a></td>
<td class="nump">$ 11,737<span></span>
</td>
<td class="num">$ (551)<span></span>
</td>
<td class="nump">$ 345,191<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract', window );"><strong>Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate', window );">Statutory rate</a></td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
<td class="nump">21.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes', window );">State income tax net of federal benefit</a></td>
<td class="nump">5.30%<span></span>
</td>
<td class="num">(14.70%)<span></span>
</td>
<td class="nump">28.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential', window );">Foreign</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.50%)<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance', window );">Net change in valuation allowance</a></td>
<td class="num">(40.70%)<span></span>
</td>
<td class="num">(9.90%)<span></span>
</td>
<td class="num">(342.50%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsPercent', window );">Loss on debt transactions</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.90%)<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits', window );">Tax credits</a></td>
<td class="nump">15.40%<span></span>
</td>
<td class="nump">79.60%<span></span>
</td>
<td class="nump">14.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationPriorYearIncomeTaxes', window );">Deferred tax true-up</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.10%<span></span>
</td>
<td class="nump">0.20%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate', window );">Tax rate change</a></td>
<td class="nump">1.20%<span></span>
</td>
<td class="num">(44.00%)<span></span>
</td>
<td class="nump">24.50%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent', window );">Non-deductible compensation</a></td>
<td class="num">(1.20%)<span></span>
</td>
<td class="num">(17.40%)<span></span>
</td>
<td class="num">(5.90%)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther', window );">Other non-deductible items</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="num">(0.30%)<span></span>
</td>
<td class="num">(0.10%)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="num">(5.40%)<span></span>
</td>
<td class="num">(16.20%)<span></span>
</td>
<td class="num">(13.00%)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent', window );">Impacts from Akcea Merger</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">16.40%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments', window );">Other</a></td>
<td class="num">(0.10%)<span></span>
</td>
<td class="nump">5.10%<span></span>
</td>
<td class="nump">0.90%<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations', window );">Effective rate</a></td>
<td class="num">(4.50%)<span></span>
</td>
<td class="nump">1.90%<span></span>
</td>
<td class="num">(256.50%)<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to acquisition of noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to acquisition of noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationAcquisitionOfNoncontrollingInterestPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to compensation in excess of $1 million paid to any "covered employee" of the corporation under Section 162(m) of the Tax Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to compensation in excess of $1 million paid to any "covered employee" of the corporation under Section 162(m) of the Tax Act.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseExcessCompensationPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to loss on debt transactions.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsPercent">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to loss on debt transactions.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseLossOnDebtTransactionsPercent</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateContinuingOperations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateContinuingOperationsTaxRateReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of domestic federal statutory tax rate applicable to pretax income (loss).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationAtFederalStatutoryIncomeTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to changes in the valuation allowance for deferred tax assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationChangeInDeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to changes in the income tax rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationChangeInEnactedTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations applicable to statutory income tax expense (benefit) outside of the country of domicile.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationForeignIncomeTaxRateDifferential</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other nondeductible expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operation, attributable to nondeductible expense for share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationNondeductibleExpenseShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other adjustments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationOtherAdjustments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationPriorYearIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to revisions of previously reported income tax expense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationPriorYearIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations applicable to state and local income tax expense (benefit), net of federal tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationStateAndLocalIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to tax credits. Including, but not limited to, research credit, foreign tax credit, investment tax credit, and other tax credits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 6.I.Fact.4)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EffectiveIncomeTaxRateReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of income (loss) from continuing operations, including income (loss) from equity method investments, before deduction of income tax expense (benefit), and income (loss) attributable to noncontrolling interest.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 940<br> -SubTopic 20<br> -Section 25<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126941158&amp;loc=d3e41242-110953<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 6: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(10))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br><br>Reference 7: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(8))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 235<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-05(b)(2))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399901&amp;loc=d3e537907-122884<br><br>Reference 9: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 31<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8924-108599<br><br>Reference 10: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(15))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefit">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of current income tax expense (benefit) and deferred income tax expense (benefit) pertaining to continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB TOPIC 6.I.7)<br> -URI https://asc.fasb.org/extlink&amp;oid=122134291&amp;loc=d3e330036-122817<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 10<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32672-109319<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (h)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.4-08(h))<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e23780-122690<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 9<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22663-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 20<br> -Section 45<br> -Paragraph 2<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123586238&amp;loc=d3e38679-109324<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(9))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefit</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxExpenseBenefitContinuingOperationsIncomeTaxReconciliationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to increase (decrease) in the valuation allowance for deferred tax assets.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationChangeInDeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations, attributable to increase (decrease) in the income tax rates.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=d3e32059-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationChangeInEnactedTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to foreign income tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationForeignIncomeTaxRateDifferential</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of income tax expense or benefit for the period computed by applying the domestic federal statutory tax rates to pretax income from continuing operations.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationIncomeTaxExpenseBenefitAtFederalStatutoryIncomeTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other nondeductible expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationNondeductibleExpenseOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of reported income tax expense (benefit) in excess of (less than) expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operation, attributable to nondeductible expense for award under share-based payment arrangement. Includes, but is not limited to, expense determined to be nondeductible upon grant or after for award under share-based payment arrangement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationNondeductibleExpenseShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationOtherAdjustments">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other adjustments.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationOtherAdjustments</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to revisions of previously reported income tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationPriorYearIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to state and local income tax expense (benefit).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationStateAndLocalIncomeTaxes</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxReconciliationTaxCredits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to tax credits. Including, but not limited to, research credit, foreign tax credit, investment tax credit, and other tax credits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 12<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32687-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxReconciliationTaxCredits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
</div>
</body>
</html>
</TEXT>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>102
<FILENAME>R66.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
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<html>
<head>
<title></title>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630367085472">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Deferred Tax Assets and Liabilities (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGrossAbstract', window );"><strong>Deferred Tax Assets [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards', window );">Net operating loss carryovers</a></td>
<td class="nump">$ 87,802<span></span>
</td>
<td class="nump">$ 85,600<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards', window );">Tax credits</a></td>
<td class="nump">277,436<span></span>
</td>
<td class="nump">269,538<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsDeferredIncome', window );">Deferred revenue</a></td>
<td class="nump">85,700<span></span>
</td>
<td class="nump">104,330<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost', window );">Stock-based compensation</a></td>
<td class="nump">86,983<span></span>
</td>
<td class="nump">86,611<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets', window );">Intangible and capital assets</a></td>
<td class="nump">104,649<span></span>
</td>
<td class="nump">92,542<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsFinancingArrangements', window );">Convertible debt</a></td>
<td class="nump">34,384<span></span>
</td>
<td class="nump">45,681<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsInterestExpenseLimitation', window );">Interest expense limitation</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">6,996<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses', window );">Capitalized research and development expenses</a></td>
<td class="nump">119,635<span></span>
</td>
<td class="nump">0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsLeasingArrangements', window );">Long-term lease liabilities</a></td>
<td class="nump">45,612<span></span>
</td>
<td class="nump">5,119<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsOther', window );">Other</a></td>
<td class="nump">15,813<span></span>
</td>
<td class="nump">9,929<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsGross', window );">Total deferred tax assets</a></td>
<td class="nump">858,014<span></span>
</td>
<td class="nump">706,346<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesAbstract', window );"><strong>Deferred Tax Liabilities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment', window );">Fixed assets</a></td>
<td class="num">(4,475)<span></span>
</td>
<td class="num">(3,303)<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesLeasingArrangements', window );">Right-of-use assets</a></td>
<td class="num">(44,504)<span></span>
</td>
<td class="num">(4,159)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxLiabilitiesOther', window );">Other</a></td>
<td class="num">(313)<span></span>
</td>
<td class="num">(1,111)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance', window );">Net deferred tax asset</a></td>
<td class="nump">808,722<span></span>
</td>
<td class="nump">697,773<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsValuationAllowance', window );">Valuation allowance</a></td>
<td class="num">(808,722)<span></span>
</td>
<td class="num">(697,773)<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DeferredTaxAssetsLiabilitiesNet', window );">Total net deferred tax assets and liabilities</a></td>
<td class="nump">0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease', window );">Increase in valuation allowance</a></td>
<td class="nump">$ 111,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to capitalized research and development expenses.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsCapitalizedResearchAndDevelopmentExpenses</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsFinancingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from financing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsFinancingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsInterestExpenseLimitation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from a limitation on interest expense.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsInterestExpenseLimitation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsLeasingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to leasing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsLeasingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the net amount of deferred tax assets (before reduction for valuation allowance) and liabilities as of the balance sheet date, which result from applying the applicable enacted tax rate to net temporary differences and carryforwards pertaining to assets or liabilities.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_DeferredTaxAssetsLiabilitiesNetBeforeValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsDeferredIncome">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from deferred income.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsDeferredIncome</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from intangible assets including goodwill.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGoodwillAndIntangibleAssets</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGross">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences and carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGross</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsGrossAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsGrossAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsLiabilitiesNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after allocation of valuation allowances and deferred tax liability, of deferred tax asset attributable to deductible differences and carryforwards, without jurisdictional netting.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsLiabilitiesNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsOperatingLossCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible operating loss carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsOperatingLossCarryforwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before allocation of valuation allowance, of deferred tax asset attributable to deductible temporary differences, classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsTaxCreditCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, before allocation of a valuation allowances, of deferred tax assets attributable to deductible tax credit carryforwards including, but not limited to, research, foreign, general business, alternative minimum tax, and other deductible tax credit carryforwards.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32559-109319<br><br>Reference 3: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsTaxCreditCarryforwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount before allocation of valuation allowances of deferred tax asset attributable to deductible temporary differences from share-based compensation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsTaxDeferredExpenseCompensationAndBenefitsShareBasedCompensationCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxAssetsValuationAllowance">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax assets for which it is more likely than not that a tax benefit will not be realized.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32537-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxAssetsValuationAllowance</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesLeasingArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences from leasing arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesLeasingArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesOther">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences classified as other.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesOther</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of deferred tax liability attributable to taxable temporary differences from property, plant, and equipment.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 6<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32621-109319<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32632-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DeferredTaxLiabilitiesPropertyPlantAndEquipment</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) in valuation and qualifying accounts and reserves.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 235<br> -SubTopic 10<br> -Section S99<br> -Paragraph 4<br> -Subparagraph (SX 210.12-09)<br> -URI https://asc.fasb.org/extlink&amp;oid=120395691&amp;loc=d3e24092-122690<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ValuationAllowancesAndReservesPeriodIncreaseDecrease</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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</div>
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</TEXT>
</DOCUMENT>
<DOCUMENT>
<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<body>
<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375118704">
<tr>
<th class="tl" colspan="1" rowspan="1"><div style="width: 200px;"><strong>Income Taxes, Tax Credit Carryforwards (Details)<br> $ in Millions</strong></div></th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember', window );">Federal [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">$ 242.8<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember', window );">Federal [Member] | Research and Development [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardLineItems', window );"><strong>Tax Credit Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">224.9<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember', window );">California [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwardsLineItems', window );"><strong>Operating Loss Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingLossCarryforwards', window );">Net operating loss carryforwards</a></td>
<td class="nump">461.3<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember', window );">California [Member] | Research and Development [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardLineItems', window );"><strong>Tax Credit Carryforwards [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TaxCreditCarryforwardAmount', window );">Tax credit carryforwards</a></td>
<td class="nump">$ 110.7<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLossCarryforwards">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of operating loss carryforward, before tax effects, available to reduce future taxable income under enacted tax laws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32559-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLossCarryforwards</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingLossCarryforwardsLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingLossCarryforwardsLineItems</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TaxCreditCarryforwardAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of the tax credit carryforward, before tax effects, available to reduce future taxable income under enacted tax laws.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32559-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TaxCreditCarryforwardAmount</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TaxCreditCarryforwardLineItems">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Line items represent financial concepts included in a table. These concepts are used to disclose reportable information associated with domain members defined in one or many axes to the table.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TaxCreditCarryforwardLineItems</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_InternalRevenueServiceIRSMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TaxCreditCarryforwardAxis=us-gaap_ResearchMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TaxCreditCarryforwardAxis=us-gaap_ResearchMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeTaxAuthorityNameAxis=us-gaap_CaliforniaFranchiseTaxBoardMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<DOCUMENT>
<TYPE>XML
<SEQUENCE>104
<FILENAME>R68.htm
<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<body>
<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375304592">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Income Taxes, Gross Unrecognized Tax Benefits (Details) - USD ($)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward', window );"><strong>Gross Unrecognized Tax Benefits [Roll Forward]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Beginning balance of unrecognized tax benefits</a></td>
<td class="nump">$ 55,085<span></span>
</td>
<td class="nump">$ 54,163<span></span>
</td>
<td class="nump">$ 69,784<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions', window );">Decrease for prior period tax positions</a></td>
<td class="num">(267)<span></span>
</td>
<td class="num">(695)<span></span>
</td>
<td class="num">(24,154)<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions', window );">Increase for prior period tax positions</a></td>
<td class="nump">259<span></span>
</td>
<td class="nump">263<span></span>
</td>
<td class="nump">7,023<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions', window );">Increase for current period tax positions</a></td>
<td class="nump">1,490<span></span>
</td>
<td class="nump">1,354<span></span>
</td>
<td class="nump">1,510<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefits', window );">Ending balance of unrecognized tax benefits</a></td>
<td class="nump">56,567<span></span>
</td>
<td class="nump">55,085<span></span>
</td>
<td class="nump">54,163<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate', window );">Unrecognized tax benefits that could impact effective tax rate, if recognized</a></td>
<td class="nump">6,200<span></span>
</td>
<td class="nump">6,200<span></span>
</td>
<td class="nump">6,400<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DecreaseInUnrecognizedTaxBenefitsIsReasonablyPossible', window );">Decrease in unrecognized tax benefits that is reasonably possible</a></td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense', window );">Interest and penalties on gross unrecognized tax benefits</a></td>
<td class="nump">$ 800<span></span>
</td>
<td class="nump">$ 500<span></span>
</td>
<td class="nump">$ 300<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DecreaseInUnrecognizedTaxBenefitsIsReasonablyPossible">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease reasonably possible in the next twelve months for the unrecognized tax benefit.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (d)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32718-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DecreaseInUnrecognizedTaxBenefitsIsReasonablyPossible</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>A roll forward is a reconciliation of a concept from the beginning of a period to the end of a period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ReconciliationOfUnrecognizedTaxBenefitsExcludingAmountsPertainingToExaminedTaxReturnsRollForward</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefits">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of unrecognized tax benefits.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 45<br> -Paragraph 10B<br> -URI https://asc.fasb.org/extlink&amp;oid=123427490&amp;loc=SL37586934-109318<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefits</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of decrease in unrecognized tax benefits resulting from tax positions taken in prior period tax returns.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsDecreasesResultingFromPriorPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of expense for interest on an underpayment of income taxes and penalties related to a tax position claimed or expected to be claimed in the tax return.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=d3e32718-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in unrecognized tax benefits resulting from tax positions that have been or will be taken in current period tax return.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromCurrentPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase in unrecognized tax benefits resulting from tax positions taken in prior period tax returns.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (a)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsIncreasesResultingFromPriorPeriodTaxPositions</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The total amount of unrecognized tax benefits that, if recognized, would affect the effective tax rate.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 740<br> -SubTopic 10<br> -Section 50<br> -Paragraph 15A<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=121826272&amp;loc=SL6600010-109319<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630356966416">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Biogen (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="6">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Sep. 30, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2012 </div>
<div>USD ($) </div>
<div>Program</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Sep. 30, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jun. 30, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2018 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Jan. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Apr. 30, 2018 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid', window );">Maximum amount of annual sales on which royalty payments are paid</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Minimum [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 475,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaMember', window );">SPINRAZA [Member] | Maximum [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack', window );">Maximum royalty payments made before royalty interest reverts back</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 550,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_SpinrazaRoyaltiesMember', window );">SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">242,314<span></span>
</td>
<td class="nump">267,776<span></span>
</td>
<td class="nump">286,583<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">364,565<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">366,700<span></span>
</td>
<td class="nump">428,800<span></span>
</td>
<td class="nump">$ 408,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 351,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 407,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 351,200<span></span>
</td>
<td class="nump">$ 407,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">62.00%<span></span>
</td>
<td class="nump">53.00%<span></span>
</td>
<td class="nump">56.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 3,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | SPINRAZA Royalties [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">242,300<span></span>
</td>
<td class="nump">$ 267,800<span></span>
</td>
<td class="nump">$ 286,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationsMember', window );">Biogen [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">124,400<span></span>
</td>
<td class="nump">161,000<span></span>
</td>
<td class="nump">122,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | SPINRAZA Royalties [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationSpinrazaMember', window );">SPINRAZA [Member] | R&amp;D Revenue [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax', window );">Cumulative revenue earned</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">425,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">425,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember', window );">New Antisense Medicines for the Treatment of SMA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 85,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">180,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaborationNewAntisenseMedicinesForTreatmentOfSmaMember', window );">New Antisense Medicines for the Treatment of SMA [Member] | ION306 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">555,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">555,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">110,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">400,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2018StrategicNeurologyMember', window );">2018 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 375,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 552,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_TermOfCollaborationAgreement', window );">Term of collaboration agreement</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">10 years<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock', window );">Upfront payment received, including purchase of stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,000,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProceedsFromIssuanceOfCommonStock', window );">Proceeds from issuance of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 625,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageCashPremiumPaidOnSharesPurchased', window );">Percentage cash premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration', window );">Maximum amount of payments receivable per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 270,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration', window );">Maximum amount of license fees per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of development milestone payments per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">105,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments per medicine over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PremiumPaidOnSharesPurchased', window );">Premium paid on shares purchased</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 177,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">616,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">616,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation', window );">Milestone payments achieved and included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 23,000<span></span>
</td>
<td class="nump">11,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">300,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 16,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 16,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of payments receivable per antisense molecule over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of license fees per antisense molecule over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of development milestone payments per antisense molecule over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">60,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments per antisense molecule over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 9,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | Medicines for Parkinson's Disease [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | Medicines for ALS [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember', window );">2013 Strategic Neurology [Member] | Medicines for Multiple System Atrophy [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced', window );">Number of medicines currently being advanced | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
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<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">210,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">210,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | IONIS-MAPT [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">57,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">57,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation', window );">Milestone payments achieved and included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 19,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2012NeurologyMember', window );">2012 Neurology [Member] | ION582 [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation', window );">Milestone payments achieved and included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 14,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 20,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativeRevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of annual sales on which royalty payments are paid under the royalty purchase agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesPerAntisenseMoleculeOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerAntisenseMoleculeOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivablePerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received for each antisense molecule that is chosen for drug discovery and development over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsPerAntisenseMoleculeOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received for each medicine that achieves marketing approval over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of upfront payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum royalty payments under the royalty purchase agreement made before royalty interest reverts back to the Company.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Milestone payments achieved under the collaboration agreement during the period and included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MilestonePaymentsAchievedAndIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMedicinesCurrentlyBeingAdvanced">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of medicines currently being advanced under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMedicinesCurrentlyBeingAdvanced</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of programs under which medicines are to be developed and commercialized under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfProgramsUnderWhichMedicinesAreToBeDevelopedAndCommercialized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageCashPremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage cash premium paid per share of the Company's common stock under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageCashPremiumPaidOnSharesPurchased</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumPaidOnSharesPurchased">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash premium paid on the purchase of the Company's common stock under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PremiumPaidOnSharesPurchased</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_TermOfCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Term of the collaboration agreement, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents the reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_TermOfCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:durationItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceivedIncludingPurchaseOfStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The total amount of the upfront payment received, including the purchase of shares of the Company's stock, under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceivedIncludingPurchaseOfStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProceedsFromIssuanceOfCommonStock">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the additional capital contribution to the entity.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 230<br> -SubTopic 10<br> -Section 45<br> -Paragraph 14<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126954810&amp;loc=d3e3255-108585<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProceedsFromIssuanceOfCommonStock</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_SpinrazaMember</td>
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<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BiogenCollaboration2013StrategicNeurologyMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630364824272">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="2">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
<th class="th">
<div>Jul. 31, 2015 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>Component</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">13.00%<span></span>
</td>
<td class="nump">31.00%<span></span>
</td>
<td class="nump">12.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember', window );">AstraZeneca [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 79,200<span></span>
</td>
<td class="nump">$ 254,600<span></span>
</td>
<td class="nump">$ 88,000<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">3,600,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">485,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates', window );">Royalty percentage received on sales of medicine in U.S.</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMaterialComponents', window );">Number of material components | Component</a></td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner', window );">Percentage of costs associated with ongoing global Phase 3 development program paid by AstraZeneca</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">55.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration [Member] | Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases Collaboration [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,800,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2,900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,500,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 65,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">10,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases Collaboration [Member] | Minimum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember', window );">Cardiovascular, Renal and Metabolic Diseases Collaboration [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation', window );">Cumulative payments included in transaction price for performance obligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative payments received since inception of the collaboration agreement included in the transaction price for the performance obligation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsIncludedInTransactionPriceForPerformanceObligation</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMaterialComponents">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of material components identified in the collaboration agreement under Accounting Standards Codification (ASC) 808, Collaborative Arrangements.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMaterialComponents</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage of costs associated with the ongoing global Phase 3 development program paid by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on sales of a medicine in the United States by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnSalesOfMedicineInUnitedStates</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationsMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember</td>
</tr>
<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationCardiovascularRenalAndMetabolicDiseasesMember</td>
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<tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630356923264">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, GSK (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jan. 31, 2023 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Sep. 30, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Medicine</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfMedicinesBeingDeveloped', window );">Number of medicines currently being developed | Medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 260,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">42,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">120,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">50,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 15,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember', window );">GSK [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 200<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfMedicinesBeingDeveloped">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of medicines currently being developed under the collaboration agreement(s).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfMedicinesBeingDeveloped</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_GlaxoSmithKlineCollaborationMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
</div></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SubsequentEventTypeAxis=us-gaap_SubsequentEventMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
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<head>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630368774400">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Novartis (Details)<br> $ in Thousands, shares in Millions</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Aug. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Mar. 31, 2017 </div>
<div>USD ($) </div>
<div>PerformanceObligation </div>
<div>shares</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th"><div>Jan. 31, 2023</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember', window );">Pelacarsen API [Member] | Subsequent Event [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine', window );">Percentage of royalty payments paid to Royalty Pharma on annual sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25.00%<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">900,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_UpfrontPaymentReceived', window );">Upfront payment received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">290,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">360,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">275,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues', window );">Shares issued (in shares) | shares</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid', window );">Proceeds from sale of common stock</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 100,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 108,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PremiumReceivedOnSharesIssued', window );">Premium received on shares issued</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">28,400<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture', window );">Potential premium received if common stock is purchased in the future</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">5,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">3.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | R&amp;D Services for Pelacarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">64,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | R&amp;D Services for Olezarsen [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">40,100<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | Pelacarsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicine', window );">Royalty percentage received on sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PercentageEnrollmentInPhase3Study', window );">Percentage enrollment in Lp(a) HORIZON Phase 3 cardiovascular outcome study</a></td>
<td class="nump">50.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 25,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | Olezarsen API [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 2,800<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_NovartisCollaborationMember', window );">Novartis [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 200<span></span>
</td>
<td class="nump">$ 25,500<span></span>
</td>
<td class="nump">$ 1,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageEnrollmentInPhase3Study">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Percentage enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageEnrollmentInPhase3Study</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The percentage of royalty payments paid on annual sales of medicine.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The potential premium received if common stock is purchased in the future under a Stock Purchase Agreement (SPA) in conjunction with the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PotentialPremiumReceivedIfCommonStockIsPurchasedInFuture</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PremiumReceivedOnSharesIssued">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The total amount of the premium received over the trading price of common stock at the time of purchase.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PremiumReceivedOnSharesIssued</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The cash inflow from the sale of common stock, including the premium paid for the purchase of common stock.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_ProceedsFromSaleOfCommonStockIncludingPremiumPaid</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_UpfrontPaymentReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of upfront payments received during the period under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_UpfrontPaymentReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_StockIssuedDuringPeriodSharesNewIssues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of new stock issued during the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(29))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section 50<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126973232&amp;loc=d3e21463-112644<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 505<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.3-04)<br> -URI https://asc.fasb.org/extlink&amp;oid=120397183&amp;loc=d3e187085-122770<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02(28))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_StockIssuedDuringPeriodSharesNewIssues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_PelacarsenActivePharmaceuticalIngredientMember">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630364660320">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Roche (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">1 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Jul. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($) </div>
<div>Indication</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2019 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Oct. 31, 2018 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
<th class="th">
<div>Apr. 30, 2013 </div>
<div>USD ($) </div>
<div>PerformanceObligation</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 22,400<span></span>
</td>
<td class="nump">$ 31,600<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">11.00%<span></span>
</td>
<td class="nump">2.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationsMember', window );">Roche [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 67,200<span></span>
</td>
<td class="nump">$ 17,200<span></span>
</td>
<td class="nump">$ 5,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationHuntingtonsDiseaseMember', window );">Collaboration to Develop Treatments for Huntington's Disease with Roche [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">395,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">30,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">45,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">70,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">170,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">80,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration', window );">Maximum amount of milestone payments for each additional medicine successfully developed over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">136,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">150,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">17,500<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 30,000<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration', window );">Maximum amount of payments receivable over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">810,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration', window );">Maximum amount of upfront payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration', window );">Maximum amount of license fees over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of development milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">145,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of regulatory milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">279,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration', window );">Maximum amount of sales milestone payments over term of collaboration</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">280,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsReceived', window );">Cumulative payments received</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">130,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NextPaymentToBeAchieved', window );">Next payment to be achieved</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 90,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations', window );">Number of separate performance obligations | PerformanceObligation</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RevenueFromContractWithCustomerTransactionPrice', window );">Transaction price</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 75,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine', window );">Royalty percentage received on net sales of medicine</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">20.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 35,000<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member] | GA [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_RocheCollaborationIonisFbLForComplementMediatedDiseasesMember', window );">IONIS-FB-L for Complement-Mediated Diseases [Member] | IgAN [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfDiseaseIndications', window );">Number of disease indications | Indication</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">1<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsReceived">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments received under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsReceived</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of development milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of license fees to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of milestone payments to be received for each medicine that is successfully developed over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfMilestonePaymentsPerMedicineOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of payments the Company is eligible to receive over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of regulatory milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of sales milestone payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The maximum amount of upfront payments to be received over the term of the collaboration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NextPaymentToBeAchieved">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The next payment to be achieved under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NextPaymentToBeAchieved</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfDiseaseIndications">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of disease indications for which studies are currently being conducted under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfDiseaseIndications</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of separate performance obligations under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RevenueFromContractWithCustomerTransactionPrice">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of consideration the Company earned or is eligible to earn under the collaboration agreement, including any variable consideration.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RevenueFromContractWithCustomerTransactionPrice</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of a medicine by a collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td><strong> Name:</strong></td>
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, PTC Therapeutics (Details)<br></strong></div></th>
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<tr><th class="th"><div>Dec. 31, 2022</div></th></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Royalty percentage received on the net sales of each medicine from the collaboration partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375215792">
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<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Bicycle License Agreement (Details) - Bicycle License Agreement [Member] - USD ($)<br> $ in Millions</strong></div></th>
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<th class="th"><div>Jul. 31, 2021</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpense', window );">R&amp;D expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 34.8<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CumulativePaymentsMade', window );">Cumulative payments made</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 46.6<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
</table>
<div style="display: none;">
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CumulativePaymentsMade">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Cumulative amount of payments made under the collaboration agreement as of the end of the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CumulativePaymentsMade</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_InvestmentInEquitySecuritiesFvNi">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Acquisition of investment in equity security measured at fair value with change in fair value recognized in net income (FV-NI).</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_InvestmentInEquitySecuritiesFvNi</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Period after completion of initial public offering by an equity investee and restriction to sell equity holding in the investee, in 'PnYnMnDTnHnMnS' format, for example, 'P1Y5M13D' represents reported fact of one year, five months, and thirteen days.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_LockUpAgreementTermOfTradingRestriction</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<tr>
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<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentsMadeUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Represents the cash outflow for payments made under the collaboration agreement for the reimbursement of support received in connection with the Company's Huntington's disease program.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentsMadeUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpense">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The aggregate costs incurred (1) in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or (2) to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects, including the costs of developing computer software up to the point in time of achieving technological feasibility, and costs allocated in accounting for a business combination to in-process projects deemed to have no alternative future use.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 912<br> -SubTopic 730<br> -Section 25<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6472174&amp;loc=d3e58812-109433<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 985<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6501960&amp;loc=d3e128462-111756<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpense</td>
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<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_BicycleCollaborationMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630379885584">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Metagenomi License Agreement (Details) - Metagenomi License Agreement [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Nov. 30, 2022 </div>
<div>Target</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_PaymentToLicenseIntellectualProperty', window );">Payment to license intellectual property | $</a></td>
<td class="nump">$ 80<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost', window );">Research and development expense | $</a></td>
<td class="nump">$ 80<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_MetagenomiCollaborationMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized', window );">Number of targets to be researched, developed and commercialized | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized', window );">Number of additional targets to be researched, developed and commercialized | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
</table>
<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of additional targets to be researched, developed and commercialized under the collaboration agreement upon achievement of certain development milestones.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfAdditionalTargetsToBeResearchedDevelopedAndCommercialized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td>xbrli:integerItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of targets to be researched, developed and commercialized under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTargetsToBeResearchedDevelopedAndCommercialized</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>xbrli:integerItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_PaymentToLicenseIntellectualProperty">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cash outflow to license intellectual property under a collaboration and license agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_PaymentToLicenseIntellectualProperty</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The costs incurred in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects, excluding in-process research and development acquired in a business combination consummated during the period. Excludes software research and development, which has a separate concept.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_MetagenomiCollaborationMember</td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630378120944">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Collaborative Arrangements and Licensing Agreements, Alnylam Pharmaceuticals, Inc. (Details)<br> $ in Thousands</strong></div></th>
<th class="th" colspan="1">3 Months Ended</th>
<th class="th" colspan="4">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2021 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2020 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Dec. 31, 2015 </div>
<div>Target </div>
<div>Program</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 587,367<span></span>
</td>
<td class="nump">$ 810,456<span></span>
</td>
<td class="nump">$ 729,264<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember', window );">R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">284,009<span></span>
</td>
<td class="nump">468,061<span></span>
</td>
<td class="nump">$ 364,565<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticPrograms', window );">Number of therapeutic programs | Program</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement', window );">Number of therapeutic targets granted to Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement', window );">Number of unnamed therapeutic targets granted to Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">2<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement', window );">Number of therapeutic targets granted by Ionis | Target</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LitigationSettlementAmountAwardedFromOtherParty', window );">Award from arbitration panel</a></td>
<td class="nump">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="nump">$ 41,200<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ContractWithCustomerLiability', window );">Deferred revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member] | Revenue [Member] | Strategic Partner [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ConcentrationRiskPercentage1', window );">Concentration percentage</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">7.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember', window );">Alnylam [Member] | R&amp;D Revenue [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract', window );"><strong>Collaborative Arrangement and Licensing Agreement [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 21,400<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 47,900<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_CollaborativeArrangementAndLicensingAgreementAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_CollaborativeArrangementAndLicensingAgreementAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTherapeuticPrograms">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic programs with exclusive license rights under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticPrograms</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic targets granted by the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of therapeutic targets granted to the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfTherapeuticTargetsGrantedToPartnerUnderCollaborationAgreement</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The number of unnamed therapeutic targets granted by the partner under the collaboration agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_NumberOfUnnamedTherapeuticTargetsGrantedByPartnerUnderCollaborationAgreement</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>ions_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:integerItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskPercentage1">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>For an entity that discloses a concentration risk in relation to quantitative amount, which serves as the "benchmark" (or denominator) in the equation, this concept represents the concentration percentage derived from the division.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 18<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6351-108592<br><br>Reference 3: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13531-108611<br><br>Reference 4: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 825<br> -SubTopic 10<br> -Section 50<br> -Paragraph 21<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=123594938&amp;loc=d3e13537-108611<br><br>Reference 5: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 275<br> -SubTopic 10<br> -Section 50<br> -Paragraph 20<br> -URI https://asc.fasb.org/extlink&amp;oid=99393423&amp;loc=d3e6404-108592<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskPercentage1</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:percentItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ContractWithCustomerLiability">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of obligation to transfer good or service to customer for which consideration has been received or is receivable.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130531-203044<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130549-203045<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126919976&amp;loc=SL49130532-203044<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ContractWithCustomerLiability</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>instant</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LitigationSettlementAmountAwardedFromOtherParty">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount awarded from other party in judgment or settlement of litigation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LitigationSettlementAmountAwardedFromOtherParty</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, excluding tax collected from customer, of revenue from satisfaction of performance obligation by transferring promised good or service to customer. Tax collected from customer is tax assessed by governmental authority that is both imposed on and concurrent with specific revenue-producing transaction, including, but not limited to, sales, use, value added and excise.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 40<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9031-108599<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 32<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8933-108599<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130543-203045<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 22<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8736-108599<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9054-108599<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 606<br> -SubTopic 10<br> -Section 50<br> -Paragraph 5<br> -URI https://asc.fasb.org/extlink&amp;oid=126920106&amp;loc=SL49130545-203045<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 924<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SAB Topic 11.L)<br> -URI https://asc.fasb.org/extlink&amp;oid=6472922&amp;loc=d3e499488-122856<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_ProductOrServiceAxis=ions_ResearchAndDevelopmentRevenueMember</td>
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<tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_TypeOfArrangementAxis=ions_AlnylamCollaborationMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByBenchmarkAxis=us-gaap_RevenueFromContractWithCustomerMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
<td></td>
</tr>
</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ConcentrationRiskByTypeAxis=us-gaap_CustomerConcentrationRiskMember</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td></td>
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630375061520">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Employment Benefits (Details) - USD ($)<br></strong></div></th>
<th class="th" colspan="3">12 Months Ended</th>
</tr>
<tr>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">$ 5,600,000<span></span>
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<td class="nump">$ 5,500,000<span></span>
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<td class="nump">$ 5,700,000<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="nump">20,500<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_RangeAxis=srt_MaximumMember', window );">Maximum [Member]</a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract', window );"><strong>Employee Benefits [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount', window );">Employee contribution limit per calendar year</a></td>
<td class="nump">$ 27,000<span></span>
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<td class="text">&#160;<span></span>
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<td class="text">&#160;<span></span>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DefinedContributionPlanCostRecognized">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of cost for defined contribution plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 715<br> -SubTopic 70<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=49170846&amp;loc=d3e28014-114942<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanCostRecognized</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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</table></div>
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</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Maximum amount the employee may contribute to a defined contribution plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_DefinedContributionPlanMaximumAnnualContributionsPerEmployeeAmount</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>duration</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GeneralDiscussionOfPensionAndOtherPostretirementBenefitsAbstract</td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MinimumMember</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td>na</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_srt_RangeAxis=srt_MaximumMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
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<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">srt_RangeAxis=srt_MaximumMember</td>
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<DOCUMENT>
<TYPE>XML
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<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630379885168">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Legal Proceedings (Details) - John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al. [Member]<br> $ in Millions</strong></div></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1">12 Months Ended</th>
</tr>
<tr>
<th class="th">
<div>Jun. 03, 2022 </div>
<div>USD ($)</div>
</th>
<th class="th">
<div>Aug. 05, 2021 </div>
<div>Plaintiff</div>
</th>
<th class="th">
<div>Dec. 31, 2022 </div>
<div>USD ($)</div>
</th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyClaimsQuantitiesAbstract', window );"><strong>Legal Procedings [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyNumberOfPlaintiffs', window );">Number of plaintiffs | Plaintiff</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">4<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LitigationSettlementAmountAwardedToOtherParty', window );">Settlement agreement</a></td>
<td class="nump">$ 12.5<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
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<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_srt_LitigationCaseAxis=ions_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember', window );">Other Expense [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_LossContingencyClaimsQuantitiesAbstract', window );"><strong>Legal Procedings [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_GainLossRelatedToLitigationSettlement', window );">Net settlement expense</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">$ 7.7<span></span>
</td>
</tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_GainLossRelatedToLitigationSettlement">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) recognized in settlement of litigation and insurance claims. Excludes claims within an insurance entity's normal claims settlement process.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 450<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=121557415&amp;loc=d3e14326-108349<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_GainLossRelatedToLitigationSettlement</td>
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<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LitigationSettlementAmountAwardedToOtherParty">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount awarded to other party in judgment or settlement of litigation.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LitigationSettlementAmountAwardedToOtherParty</td>
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<td><strong> Period Type:</strong></td>
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LossContingencyClaimsQuantitiesAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_LossContingencyNumberOfPlaintiffs">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of plaintiffs that have filed claims pertaining to a loss contingency.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 450<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121557415&amp;loc=d3e14435-108349<br><br>Reference 2: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 450<br> -SubTopic 20<br> -Section 50<br> -Paragraph 9<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=121557415&amp;loc=d3e14557-108349<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_LossContingencyNumberOfPlaintiffs</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<td><strong> Period Type:</strong></td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncomeStatementLocationAxis=us-gaap_OtherNonoperatingIncomeExpenseMember">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Details</a><div><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncomeStatementLocationAxis=us-gaap_OtherNonoperatingIncomeExpenseMember</td>
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<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td></td>
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<td><strong> Data Type:</strong></td>
<td>na</td>
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<td><strong> Balance Type:</strong></td>
<td></td>
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<tr>
<td><strong> Period Type:</strong></td>
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<TYPE>XML
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<DESCRIPTION>IDEA: XBRL DOCUMENT
<TEXT>
<html>
<head>
<title></title>
<link rel="stylesheet" type="text/css" href="include/report.css">
<script type="text/javascript" src="Show.js">/* Do Not Remove This Comment */</script><script type="text/javascript">
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<span style="display: none;">v3.22.4</span><table class="report" border="0" cellspacing="2" id="idm139630366180384">
<tr>
<th class="tl" colspan="1" rowspan="2"><div style="width: 200px;"><strong>Fourth Quarter Financial Data (Unaudited) (Details) - USD ($)<br> $ / shares in Units, shares in Thousands, $ in Thousands</strong></div></th>
<th class="th" colspan="4">3 Months Ended</th>
<th class="th" colspan="3">12 Months Ended</th>
<th class="th" colspan="1"></th>
<th class="th" colspan="1"></th>
</tr>
<tr>
<th class="th" colspan="2"><div>Dec. 31, 2022</div></th>
<th class="th" colspan="2"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2022</div></th>
<th class="th"><div>Dec. 31, 2021</div></th>
<th class="th"><div>Dec. 31, 2020</div></th>
<th class="th"><div>Apr. 30, 2021</div></th>
<th class="th"><div>Dec. 31, 2019</div></th>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="nump">$ 151,890<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[1]</sup></td>
<td class="nump">$ 440,006<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_CostsAndExpenses', window );">Operating expenses</a></td>
<td class="nump">359,909<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[2]</sup></td>
<td class="nump">219,403<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 997,558<span></span>
</td>
<td class="nump">$ 840,642<span></span>
</td>
<td class="nump">$ 901,346<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_OperatingIncomeLoss', window );">Loss from operations</a></td>
<td class="num">(208,019)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">220,603<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">(410,191)<span></span>
</td>
<td class="num">(30,186)<span></span>
</td>
<td class="num">(172,082)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ProfitLoss', window );">Net income (loss)</a></td>
<td class="num">$ (52,430)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[3]</sup></td>
<td class="nump">$ 224,613<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="num">$ (269,722)<span></span>
</td>
<td class="num">$ (28,597)<span></span>
</td>
<td class="num">$ (479,743)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareBasic', window );">Basic net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (0.37)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[5]</sup></td>
<td class="nump">$ 1.59<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[5]</sup></td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
<td class="num">$ (3.18)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_EarningsPerShareDiluted', window );">Diluted net income (loss) per share (in dollars per share)</a></td>
<td class="num">$ (0.37)<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4]</sup></td>
<td class="nump">$ 1.41<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"><sup>[4],[6]</sup></td>
<td class="num">$ (1.9)<span></span>
</td>
<td class="num">$ (0.2)<span></span>
</td>
<td class="num">$ (3.18)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SaleAndLeasebackTransactionGainLossNet', window );">Gain on sale of real estate assets</a></td>
<td class="nump">$ 150,100<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 150,135<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="nump">$ 0<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic', window );">Income (loss) available to Ionis common stockholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 224,612<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="num">$ (444,464)<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="reu">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted', window );">Net income available to Ionis common shareholders</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 226,210<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingDilutedDisclosureItemsAbstract', window );"><strong>Shares (Denominator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic', window );">Shares used in computing basic net loss per share (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">141,205<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl custom" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan', window );">Shares issuable related to our ESPP (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">34<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rou">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding', window );">Shares used in computing diluted net income per share (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">160,340<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">141,848<span></span>
</td>
<td class="nump">141,021<span></span>
</td>
<td class="nump">139,612<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0PercentMember', window );">0 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
<td class="nump">0.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 777<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities', window );">Shares issuable related to our convertible notes (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">10,936<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes0125PercentMember', window );">0.125 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="nump">0.125%<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 716<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities', window );">Shares issuable related to our convertible notes (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">6,590<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentAxis=ions_ConvertibleSeniorNotes1PercentMember', window );">1 Percent Convertible Senior Notes [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DebtInstrumentInterestRateStatedPercentage', window );">Interest rate on convertible senior notes</a></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
<td class="nump">1.00%<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract', window );"><strong>Income (Numerator) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_DilutiveSecuritiesEffectOnBasicEarningsPerShareOther', window );">Shares issuable related to our convertible notes</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 105<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities', window );">Shares issuable related to our convertible notes (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">464<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_EmployeeStockOptionMember', window );">Stock Options [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">46<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_AwardTypeAxis=us-gaap_RestrictedStockMember', window );">Restricted Stock Awards [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract', window );"><strong>Effect of Diluted Securities [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements', window );">Shares issuable related to stock-based compensation (in shares)</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">1,065<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_AstrazenecaCollaborationEplontersenMember', window );">Eplontersen Collaboration [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_Revenues', window );">Revenue</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="nump">$ 200,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="rh">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_TypeOfArrangementAxis=ions_MetagenomiCollaborationMember', window );">Metagenomi License Agreement [Member]</a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="ro">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract', window );"><strong>Fourth Quarter Financial Data (Unaudited) [Abstract]</strong></a></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr class="re">
<td class="pl" style="border-bottom: 0px;" valign="top"><a class="a" href="javascript:void(0);" onclick="Show.showAR( this, 'defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost', window );">Upfront payment</a></td>
<td class="nump">$ 80,000<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="fn" style="border-bottom: 0px;"></td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
<td class="text">&#160;<span></span>
</td>
</tr>
<tr><td colspan="10"></td></tr>
<tr><td colspan="10"><table class="outerFootnotes" width="100%">
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[1]</td>
<td style="vertical-align: top;" valign="top">Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[2]</td>
<td style="vertical-align: top;" valign="top">Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $80 million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[3]</td>
<td style="vertical-align: top;" valign="top">Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[4]</td>
<td style="vertical-align: top;" valign="top"><span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">We </span>compute net income (loss) per share independently for each quarter during <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;">the year.</span></td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[5]</td>
<td style="vertical-align: top;" valign="top">As discussed in Note 1, <span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;">Organization and Significant Accounting Policies, </span>we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.</td>
</tr>
<tr class="outerFootnote">
<td style="vertical-align: top; width: 12pt;" valign="top">[6]</td>
<td style="vertical-align: top;" valign="top">We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period</td>
</tr>
</table></td></tr>
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<div style="display: none;">
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan">
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<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of shares issuable related to employee stock purchase plan.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">ions_IncrementalCommonSharesAttributableToEmployeeStockPurchasePlan</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Total costs of sales and operating expenses for the period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03)<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<td><strong> Balance Type:</strong></td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Contractual interest rate for funds borrowed, under the debt agreement.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 20<br> -Section 50<br> -Paragraph 1B<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=123466505&amp;loc=SL123495323-112611<br><br>Reference 2: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 210<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.5-02.22(a)(1))<br> -URI https://asc.fasb.org/extlink&amp;oid=120391452&amp;loc=d3e13212-122682<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of increase (decrease) to net income used for calculating diluted earnings per share (EPS), resulting from the assumed exercise of dilutive convertible securities excluding adjustments related to ESOP convertible preferred stock, stock options, and restrictive stock units.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
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<td><strong> Data Type:</strong></td>
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</table></div>
</div></td></tr>
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<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period per each share of common stock or unit outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 4: 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_EarningsPerShareDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The amount of net income (loss) for the period available to each share of common stock or common unit outstanding during the reporting period and to each share or unit that would have been outstanding assuming the issuance of common shares or units for all dilutive potential common shares or units outstanding during the reporting period.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 52<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e4984-109258<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 7<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22644-107794<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 55<br> -Paragraph 15<br> -URI https://asc.fasb.org/extlink&amp;oid=128363288&amp;loc=d3e3842-109258<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 2<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1252-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 4<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22595-107794<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 3<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22583-107794<br><br>Reference 8: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (d)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 9: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 10: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 942<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.9-04(27))<br> -URI https://asc.fasb.org/extlink&amp;oid=120399700&amp;loc=SL114874048-224260<br><br>Reference 11: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 12: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 944<br> -SubTopic 220<br> -Section S99<br> -Paragraph 1<br> -Subparagraph (SX 210.7-04(23))<br> -URI https://asc.fasb.org/extlink&amp;oid=120400993&amp;loc=SL114874131-224263<br><br>Reference 13: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 11<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22694-107794<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 7<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1337-109256<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 815<br> -SubTopic 40<br> -Section 65<br> -Paragraph 1<br> -Subparagraph (e)(4)<br> -URI https://asc.fasb.org/extlink&amp;oid=126732423&amp;loc=SL123482106-238011<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 220<br> -SubTopic 10<br> -Section S99<br> -Paragraph 2<br> -Subparagraph (SX 210.5-03(25))<br> -URI https://asc.fasb.org/extlink&amp;oid=126953954&amp;loc=SL114868664-224227<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_EarningsPerShareDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>dtr-types:perShareItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of convertible debt securities using the if-converted method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1930-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 42<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e2029-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Additional shares included in the calculation of diluted EPS as a result of the potentially dilutive effect of share based payment arrangements using the treasury stock method.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 718<br> -SubTopic 10<br> -Section 45<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=126962052&amp;loc=d3e4991-113900<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 22<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1707-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 28A<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1500-109256<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 23<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1757-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:sharesItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities; of income (loss) available to common shareholders.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersBasic</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<tr>
<td><strong> Period Type:</strong></td>
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</table></div>
</div></td></tr>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount, after deduction of tax, noncontrolling interests, dividends on preferred stock and participating securities, and addition from assumption of issuance of common shares for dilutive potential common shares; of income (loss) available to common shareholders.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (b)(2)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1930-109256<br><br>Reference 2: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (b)(3)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1930-109256<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 60B<br> -Subparagraph (c)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=SL5780133-109256<br><br>Reference 4: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=124432515&amp;loc=d3e3550-109257<br><br>Reference 5: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (b)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1930-109256<br><br>Reference 6: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 16<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1505-109256<br><br>Reference 7: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 260<br> -SubTopic 10<br> -Section 45<br> -Paragraph 40<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126958026&amp;loc=d3e1930-109256<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDiluted</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_NetIncomeLossAvailableToCommonStockholdersDilutedAbstract</td>
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<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
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<td>xbrli:stringItemType</td>
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<td><strong> Balance Type:</strong></td>
<td>na</td>
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<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_OperatingIncomeLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The net result for the period of deducting operating expenses from operating revenues.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_OperatingIncomeLoss</td>
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<td>credit</td>
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<td><strong> Period Type:</strong></td>
<td>duration</td>
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<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ProfitLoss">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The consolidated profit or loss for the period, net of income taxes, including the portion attributable to the noncontrolling interest.</p></div>
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-Subparagraph (SX 210.13-01(a)(4)(iii)(A))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 27: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 28: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(4)(iii)(B))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 29: http://www.xbrl.org/2009/role/commonPracticeRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 210.13-01(a)(4)(ii))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442526-122756<br><br>Reference 30: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1A<br> -Subparagraph (c)(1)<br> -URI https://asc.fasb.org/extlink&amp;oid=109239629&amp;loc=SL4573702-111684<br><br>Reference 31: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4J<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591551-111686<br><br>Reference 32: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 810<br> -SubTopic 10<br> -Section 55<br> -Paragraph 4K<br> -URI https://asc.fasb.org/extlink&amp;oid=120409616&amp;loc=SL4591552-111686<br><br>Reference 33: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 250<br> -SubTopic 10<br> -Section 50<br> -Paragraph 8<br> -URI https://asc.fasb.org/extlink&amp;oid=124431687&amp;loc=d3e22658-107794<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ProfitLoss</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The costs incurred in a planned search or critical investigation aimed at discovery of new knowledge with the hope that such knowledge will be useful in developing a new product or service, a new process or technique, or in bringing about a significant improvement to an existing product or process; or to translate research findings or other knowledge into a plan or design for a new product or process or for a significant improvement to an existing product or process whether intended for sale or the entity's use, during the reporting period charged to research and development projects, excluding in-process research and development acquired in a business combination consummated during the period. Excludes software research and development, which has a separate concept.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://fasb.org/us-gaap/role/ref/legacyRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 730<br> -SubTopic 10<br> -Section 50<br> -Paragraph 1<br> -URI https://asc.fasb.org/extlink&amp;oid=6420194&amp;loc=d3e21568-108373<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_ResearchAndDevelopmentExpenseExcludingAcquiredInProcessCost</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>debit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_Revenues">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of revenue recognized from goods sold, services rendered, insurance premiums, or other activities that constitute an earning process. Includes, but is not limited to, investment and interest income before deduction of interest expense when recognized as a component of revenue, and sales and trading gain (loss).</p></div>
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-SubTopic 10<br> -Section 50<br> -Paragraph 30<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e8906-108599<br><br>Reference 14: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1B<br> -Subparagraph (SX 210.13-02(a)(5))<br> -URI https://asc.fasb.org/extlink&amp;oid=126975872&amp;loc=SL124442552-122756<br><br>Reference 15: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 280<br> -SubTopic 10<br> -Section 50<br> -Paragraph 41<br> -Subparagraph (a)<br> -URI https://asc.fasb.org/extlink&amp;oid=126901519&amp;loc=d3e9038-108599<br><br>Reference 16: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 470<br> -SubTopic 10<br> -Section S99<br> -Paragraph 1A<br> -Subparagraph (SX 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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_Revenues</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SaleAndLeasebackTransactionGainLossNet">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Amount of gain (loss) on sale and leaseback transaction from transfer of asset accounted for as sale.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ References</a><div style="display: none;"><p>Reference 1: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 40<br> -Section 50<br> -Paragraph 2<br> -Subparagraph (b)<br> -URI https://asc.fasb.org/extlink&amp;oid=128295416&amp;loc=SL77919786-209982<br><br>Reference 2: http://www.xbrl.org/2003/role/exampleRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 55<br> -Paragraph 53<br> -URI https://asc.fasb.org/extlink&amp;oid=123414884&amp;loc=SL77918982-209971<br><br>Reference 3: http://www.xbrl.org/2003/role/disclosureRef<br> -Publisher FASB<br> -Name Accounting Standards Codification<br> -Topic 842<br> -SubTopic 20<br> -Section 50<br> -Paragraph 4<br> -Subparagraph (f)<br> -URI https://asc.fasb.org/extlink&amp;oid=128292326&amp;loc=SL77918686-209980<br></p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SaleAndLeasebackTransactionGainLossNet</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:monetaryItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>credit</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_SelectedQuarterlyFinancialInformationAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_SelectedQuarterlyFinancialInformationAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- References</a><div><p>No definition available.</p></div>
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">+ Details</a><div style="display: none;"><table border="0" cellpadding="0" cellspacing="0">
<tr>
<td><strong> Name:</strong></td>
<td style="white-space:nowrap;">us-gaap_WeightedAverageNumberDilutedSharesOutstandingAdjustmentAbstract</td>
</tr>
<tr>
<td style="padding-right: 4px;white-space:nowrap;"><strong> Namespace Prefix:</strong></td>
<td>us-gaap_</td>
</tr>
<tr>
<td><strong> Data Type:</strong></td>
<td>xbrli:stringItemType</td>
</tr>
<tr>
<td><strong> Balance Type:</strong></td>
<td>na</td>
</tr>
<tr>
<td><strong> Period Type:</strong></td>
<td>duration</td>
</tr>
</table></div>
</div></td></tr>
</table>
<table border="0" cellpadding="0" cellspacing="0" class="authRefData" style="display: none;" id="defref_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding">
<tr><td class="hide"><a style="color: white;" href="javascript:void(0);" onclick="Show.hideAR();">X</a></td></tr>
<tr><td><div class="body" style="padding: 2px;">
<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>The average number of shares or units issued and outstanding that are used in calculating diluted EPS or earnings per unit (EPU), determined based on the timing of issuance of shares or units in the period.</p></div>
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<a href="javascript:void(0);" onclick="Show.toggleNext( this );">- Definition</a><div><p>Number of [basic] shares or units, after adjustment for contingently issuable shares or units and other shares or units not deemed outstanding, determined by relating the portion of time within a reporting period that common shares or units have been outstanding to the total time in that period.</p></div>
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;1. Organization and Significant Accounting Policies&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea&#x2019;s common stock below
    100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the
    period the changes occurred&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Organization and Business Activity&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We incorporated in California on January 10, 1989. In conjunction with our IPO, we reorganized as a Delaware corporation in April 1991. We
    were organized principally to develop human therapeutic medicines using antisense technology. In December 2015, we changed our name from Isis Pharmaceuticals, Inc. to Ionis Pharmaceuticals, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us
    to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Revenue Recognition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that contain multiple elements, we &lt;/span&gt;first&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; determine which elements of the collaboration
      reflect a vendor-customer relationship and therefore are within the scope of ASC &lt;/span&gt;606&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we
      consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our eplontersen collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue;
    while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as SG&amp;amp;A expense and research and development expense, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the contract&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the
    following criteria:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
            contract; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe collectability of the consideration is probable.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;2.&lt;/span&gt;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We frequently enter into a collaboration agreement in which
      we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We
      evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we
      grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant
      discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do
    not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation. Refer to the section titled, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/span&gt;, below for further discussion of a collaboration that included an upfront license payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;3.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
        agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments,
        license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the
        payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount
      method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include
      a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our
      milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;4.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We may engage a &lt;/span&gt;third&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the
      stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present
      value. The significant inputs we use to determine the projected income of a license could include&lt;/span&gt;:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated royalties we may receive from future product sales;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated contractual milestone payments we may receive;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated expenses we may incur;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated income taxes; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A discount rate.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We typically estimate the selling price of research and development, or R&amp;amp;D, services by using our internal estimates of the cost to
    perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated number of internal hours we will spend performing these services;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of API we will use.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting
    guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;5.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based
      on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given
      period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires
      us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Amendments to Agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement
        and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services
        are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the
        amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative-effect adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Multiple agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Part IV, Item 15, Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative
      Arrangements and Licensing Agreements&lt;/span&gt;, for further discussion of our 2018 Strategic Neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&lt;/span&gt;&lt;/span&gt;&#160;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are sources of revenue and when we typically recognize revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue, including royalties from
      SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began
    commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As
    a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and
    WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics
    companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In
    the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as
    distributors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of
    the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
    view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
    distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer
    obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as
    selling, general and administrative, or SG&amp;amp;A, expenses in our consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as
    discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Research and development revenue under collaboration agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;amp;D services and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We provide details about our collaboration agreements in Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;. For each collaboration, we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation
      is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they
      are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in
      the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when
      we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;amp;D services performance obligation and
      recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone to the
      transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the
    milestone event and we do not have a performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is
      because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Sublicense fees:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not
      have any performance obligations related to the sublicense.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the
    U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities
    that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#x2019;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca
    related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within one &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a"&gt;quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022,
    approximately 82.5 percent of our contracts receivables were from one significant customer. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two
    significant customers.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen
    for SPINRAZA royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.&lt;/span&gt; During the years ended December 31, 2022 and 2021, we recognized $73.5 million and $98.1 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Patent Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the
    services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in research and development expenses are costs associated with our
    partner agreements. In 2022, 2021 and 2020, patent expenses were $4.7 million, $5.3 million and $4.1 million, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign
    subsidiaries. &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net loss per share by dividing the total net loss attributable to our common stockholders by our weighted-average number
    of common shares outstanding during the period. For the years ended December 31, 2022 and 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the years ended December 31, 2022 and 2021 was $1.90 and $0.20, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the year ended December 31, 2020, we calculated total net loss attributable to our common stockholders using our net loss for Ionis on
    a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s net loss per share by the weighted average shares we owned in Akcea. As a result of
    this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share was different than net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of
    operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(246,702&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(444,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent
    shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock underlying the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022 and 2021, common stock underlying the following would also have had an anti-dilutive effect on net
    loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes; and&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally as of December 31, 2022 and 2021, we had warrants related to our 0 percent and 0.125 percent Notes outstanding. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-Based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Stock Options and Stock Purchase Rights:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended
    December 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected
    term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted to our board of directors after June 2020 fully vest after one year.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"&gt;&lt;span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"&gt;&lt;span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end
    of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the
    date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the
    second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the
    date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Part IV, Item 15, Note 5, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Stockholders&#x2019;
      Equity,&lt;/span&gt; for additional information regarding our stock-based compensation plans.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Since Akcea&#x2019;s IPO in July 2017 and prior to the Akcea Merger
      in October 2020, the shares of Akcea&#x2019;s common stock third parties owned represented an interest in Akcea&#x2019;s equity that we did not control. During this period our ownership ranged from &lt;/span&gt;68 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;77 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of
      Akcea in our consolidated financial statements. Since Akcea&#x2019;s IPO in July 2017 and through the closing of the Akcea Merger, we reflected the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock on a separate line in our
      statements of operations and a separate line within stockholders&#x2019; equity in our consolidated balance sheets. In addition, through the closing of the Akcea Merger, we recorded a noncontrolling interest adjustment to account for the stock options Akcea
      granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
      compensation expense Akcea had recognized. Additionally, w&lt;/span&gt;e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accumulated Other Comprehensive Loss&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,395&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,486&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(417&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive income (losses) for the year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,812&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,597&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(57,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;div&gt;
    &lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; text-align: right;"&gt;
            &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;
          &lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top;"&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;&lt;/div&gt;
          &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
    &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Concentration of Credit Risk&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#x2019;s, Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we
      received as part of a technology license or partner agreement. At December 31, 2022, we held equity investments in three publicly traded companies and eight
      privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment
    of the same issuer.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventories&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in
    inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and,
    as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We
    expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial
    medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical
    write-offs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,061&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,699&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,760&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,109&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;164&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,033&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated Useful&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Lives (in years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,351&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,802&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,158&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,046&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;-&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,077&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,357&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,144&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,575&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;153,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;257,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(102,653&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;155,007&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,294&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,069&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we sold the facilities and related land at our headquarters for net proceeds of $202.6 million in connection with a sale and leaseback transaction.&#160; In connection with the sale of these real estate assets, we de-recognized the related land and improvements,
    building and building improvements, which resulted in a net gain of $150.1 million that we reported in other income (expense) in our consolidated
    statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accrued Liabilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Clinical expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;116,460&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,730&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In-licensing expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,945&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,044&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,498&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,471&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,198&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,315&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,101&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88,560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Estimated Liability for Clinical Development Costs&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. &lt;/span&gt;The&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022, we had two
    outstanding convertible senior notes, our 0% Notes, which mature in April 2026, and our 0.125% Notes, which mature in December 2024. Refer to Part IV, Item 15, Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term
      Obligations and Commitments&lt;/span&gt;, for further details on our convertible senior notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives
      and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity&lt;/span&gt; accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify the
    note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an
    aggregate basis and manages our operations as a &lt;span style="-sec-ix-hidden:Fact_33bc30118e9548358994c912eadf2161"&gt;single&lt;/span&gt; operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea&#x2019;s operations into ours as of January 1, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Adopted Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities
    subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity
    securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter
    of 2022. This guidance did not have a material impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:OrganizationConsolidationBasisOfPresentationBusinessDescriptionAndAccountingPoliciesTextBlock>
    <us-gaap:ConsolidationPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_8c102e683032408d831953ba9e81ff45">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basis of Presentation&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In our consolidated financial statements we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our
    subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (&#x201c;we&#x201d;, &#x201c;us&#x201d; or &#x201c;our&#x201d;). We formed Akcea in December 2014. In July 2017, Akcea completed an initial public offering, or IPO, which reduced our ownership of Akcea&#x2019;s common stock below
    100 percent. In October 2020, we completed a merger transaction with Akcea such that following the completion of the merger, Akcea became our
    wholly owned subsidiary. We will refer to this transaction as the Akcea Merger throughout the remainder of this document. We reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the
    period the changes occurred&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;
</us-gaap:ConsolidationPolicyTextBlock>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20170630_OwnershipAxis_AkceaTherapeuticsIncMember_RangeAxis_MaximumMember"
      decimals="2"
      id="Fact_a88597664460426696b9ccf265c067d6"
      unitRef="U003">1</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:UseOfEstimates
      contextRef="c20220101to20221231"
      id="Text_1fd01a87e7da42ebb9f72e4dc40a543b">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Use of Estimates&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We prepare our consolidated financial statements in conformity with accounting principles generally accepted in the U.S. that require us
    to make estimates and assumptions that affect the amounts reported in our consolidated financial statements and accompanying notes. Actual results could differ from our estimates.&lt;/div&gt;
</us-gaap:UseOfEstimates>
    <us-gaap:RevenueFromContractWithCustomerPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_fe4f7603d54b47ad88a34d684805e9ce">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Revenue Recognition&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We generally recognize revenue when we have satisfied all contractual obligations and are reasonably assured of collecting the resulting
    receivable. We are often entitled to bill our customers and receive payment from our customers in advance of recognizing the revenue. In the instances in which we have received payment from our customers in advance of recognizing revenue, we include
    the amounts within deferred revenue in our consolidated balance sheets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At contract inception, we analyze our collaboration arrangements to assess whether such arrangements involve joint operating activities
    performed by parties that are both active participants in the activities and exposed to significant risks and rewards dependent on the commercial success of such activities and therefore within the scope of ASC Topic 808, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements&lt;/span&gt;, or ASC 808. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; does not address the recognition and measurement of collaborative arrangements and instead refers companies to use other authoritative accounting literature. For collaboration arrangements within the scope of ASC &lt;/span&gt;808&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; that contain multiple elements, we &lt;/span&gt;first&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; determine which elements of the collaboration
      reflect a vendor-customer relationship and therefore are within the scope of ASC &lt;/span&gt;606&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Revenue from Contracts with Customers&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. When we determine elements of a collaboration do not reflect a vendor-customer relationship, we
      consistently apply the reasonable and rational policy election we made by analogizing to authoritative accounting literature&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate the income statement classification for presentation of amounts due from or owed to other participants associated with
    multiple activities in a collaboration arrangement based on the nature of each separate activity. For example, in our eplontersen collaboration with AstraZeneca, we recognize funding received from AstraZeneca for co-development activities as revenue;
    while we recognize cost sharing payments to and from AstraZeneca associated with co-commercialization activities and co-medical affairs activities as SG&amp;amp;A expense and research and development expense, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Steps to Recognize Revenue&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For elements of our contractual relationships that we account for under ASC 606, we use a five-step process to determine the amount of
    revenue we should recognize and when we should recognize it. The five-step process is as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the contract&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Accounting rules require us to first determine if we have a contract with our partner, including confirming that we have met each of the
    following criteria:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We and our partner approved the contract and we are both committed to perform our obligations;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have identified our rights, our partner&#x2019;s rights and the payment terms;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have concluded that the contract has commercial substance, meaning that the risk, timing, or amount of our future cash flows is expected to change as a result of the
            contract; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We believe collectability of the consideration is probable.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;2.&lt;/span&gt;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Identify the performance obligations&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We next identify our performance obligations, which represent the distinct goods and services we are required to provide under the
    contract.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We frequently enter into a collaboration agreement in which
      we provide our partner with an option to license a medicine in the future. We may also provide our partner with an option to request that we provide additional goods or services in the future, such as active pharmaceutical ingredient, or API. We
      evaluate whether these options are material rights at the inception of the agreement. If we determine an option is a material right, we will consider the option a separate performance obligation. Historically, we have concluded that the options we
      grant to license a medicine in the future or to provide additional goods and services as requested by our partner are not material rights because these items are contingent upon future events that may not occur and are not priced at a significant
      discount. When a partner exercises its option to license a medicine or requests additional goods or services, then we identify a new performance obligation for that item&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In some cases, we deliver a license at the start of an agreement. If we determine that our partner has full use of the license and we do
    not have any additional material performance obligations related to the license after delivery, then we consider the license to be a separate performance obligation. Refer to the section titled, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/span&gt;, below for further discussion of a collaboration that included an upfront license payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;3.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Determine the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We then determine the transaction price by reviewing the amount of consideration we are eligible to earn under the collaboration
        agreement, including any variable consideration. Under our collaboration agreements, consideration typically includes fixed consideration in the form of an upfront payment and variable consideration in the form of potential milestone payments,
        license fees and royalties. At the start of an agreement, our transaction price usually consists of only the upfront payment. We do not typically include any payments we may receive in the future in our initial transaction price because the
        payments are not probable and are contingent on certain future events. We reassess the total transaction price at each reporting period to determine if we should include additional payments in the transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Milestone payments are our most common type of variable consideration. We recognize milestone payments using the most likely amount
      method because we will either receive the milestone payment or we will not, which makes the potential milestone payment a binary event. The most likely amount method requires us to determine the likelihood of earning the milestone payment. We include
      a milestone payment in the transaction price once it is probable we will achieve the milestone event. Most often, we do not consider our milestone payments probable until we or our partner achieve the milestone event because the majority of our
      milestone payments are contingent upon events that are not within our control and/ or are usually based on scientific progress which is inherently uncertain.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;4.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: left;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Allocate the transaction price&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Next, we allocate the transaction price to each of our
        performance obligations. When we have to allocate the transaction price to more than &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; performance obligation, we make estimates of the relative stand-alone
        selling price of each performance obligation because we do not typically sell our goods or services on a stand-alone basis. We then allocate the transaction price to each performance obligation based on the relative stand-alone selling price. We do
        not reallocate the transaction price after the start of an agreement to reflect subsequent changes in stand-alone selling prices.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We may engage a &lt;/span&gt;third&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; party, independent valuation specialist to assist us with determining a stand-alone selling price for collaborations in which we deliver a license at the start of an agreement. We estimate the
      stand-alone selling price of these licenses using valuation methodologies, such as the relief from royalty method. Under this method, we estimate the amount of income, net of taxes, for the license. We then discount the projected income to present
      value. The significant inputs we use to determine the projected income of a license could include&lt;/span&gt;:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated future product sales;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated royalties we may receive from future product sales;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated contractual milestone payments we may receive;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated expenses we may incur;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Estimated income taxes; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A discount rate.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We typically estimate the selling price of research and development, or R&amp;amp;D, services by using our internal estimates of the cost to
    perform the specific services. The significant inputs we use to determine the selling price of our R&amp;amp;D services include:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated number of internal hours we will spend performing these services;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work we will perform;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of work that we will contract with third parties to perform; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The estimated cost of API we will use.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For purposes of determining the stand-alone selling price of the R&amp;amp;D services we perform and the API we will deliver, accounting
    guidance requires us to include a markup for a reasonable profit margin.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;5.&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Recognize revenue&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize revenue in &lt;/span&gt;one&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; ways, over time or at a point in time. We recognize revenue over time when we are executing on our
        performance obligation over time and our partner receives benefit over time. For example, we recognize revenue over time when we provide R&amp;amp;D services. We recognize revenue at a point in time when our partner receives full use of an item at a
        specific point in time. For example, we recognize revenue at a point in time when we deliver a license or API to a partner.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For R&amp;amp;D services that we recognize over time, we measure our progress using an input method. The input methods we use are based
      on the effort we expend or costs we incur toward the satisfaction of our performance obligation. We estimate the amount of effort we expend, including the time we estimate it will take us to complete the activities, or costs we incur in a given
      period, relative to the estimated total effort or costs to satisfy the performance obligation. This results in a percentage that we multiply by the transaction price to determine the amount of revenue we recognize each period. This approach requires
      us to make numerous estimates and use significant judgement. If our estimates or judgements change over the course of the collaboration, they may affect the timing and amount of revenue that we recognize in the current and future periods.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Amendments to Agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time we amend our collaboration agreements. When this occurs, we are required to assess the following items to determine the
    accounting for the amendment:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the additional goods and/or services are distinct from the other performance obligations in the original agreement; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If the goods and/or services are sold at a stand-alone selling price.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;If we conclude the goods and/or services in the amendment are distinct from the performance obligations in the original agreement
        and at a stand-alone selling price, we account for the amendment as a separate agreement. If we conclude the goods and/or services are not distinct and are sold at a stand-alone selling price, we then assess whether the remaining goods or services
        are distinct from those already provided. If the goods and/or services are distinct from what we have already provided, then we allocate the remaining transaction price from the original agreement and the additional transaction price from the
        amendment to the remaining goods and/or services. If the goods and/or services are not distinct from what we have already provided, we update the transaction price for our single performance obligation and recognize any change in our estimated
        revenue as a cumulative-effect adjustment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="text-decoration: underline;"&gt;Multiple agreements&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we may enter into separate agreements at or near the same time with the same partner. We evaluate such agreements to
    determine whether we should account for them individually as distinct arrangements or whether the separate agreements should be combined and accounted for together. We evaluate the following to determine the accounting for the agreements:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the agreements were negotiated together with a single objective;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the amount of consideration in one contract depends on the price or performance of the other agreement; or&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Whether the goods and/or services promised under the agreements are a single performance obligation.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our evaluation involves significant judgment to determine whether a group of agreements might be so closely related that accounting
    guidance requires us to account for them as a combined arrangement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Part IV, Item 15, Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative
      Arrangements and Licensing Agreements&lt;/span&gt;, for further discussion of our 2018 Strategic Neurology collaboration with Biogen that included multiple agreements which we negotiated concurrently and in contemplation of one another.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&lt;span style="text-decoration: underline;"&gt;Our Revenue Sources&lt;/span&gt;&lt;/span&gt;&#160;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following are sources of revenue and when we typically recognize revenue.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: SPINRAZA royalties and Licensing and other royalty revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We earn commercial revenue primarily in the form of royalty payments on net sales of SPINRAZA.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize royalty revenue, including royalties from
      SPINRAZA sales, in the period in which the counterparty sells the related product and recognizes the related revenue, which in certain cases may require us to estimate our royalty revenue&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Commercial Revenue: TEGSEDI and WAYLIVRA revenue, net&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2021 and April 2021, we entered into distribution agreements with Swedish Orphan Biovitrum AB, or Sobi, in which Sobi began
    commercializing TEGSEDI and WAYLIVRA in Europe and TEGSEDI in North America, respectively. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. As
    a result of these agreements, we earn a distribution fee on net sales from Sobi for each medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration agreement with PTC Therapeutics International Limited, or PTC, PTC is responsible for commercializing TEGSEDI and
    WAYLIVRA in Latin America and Caribbean countries. Under our agreement, we started receiving royalties from PTC for TEGSEDI sales in December 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to the second quarter of 2021 in North America, we sold TEGSEDI through exclusive distribution agreements with third-party logistics
    companies, or 3PLs, that took title to TEGSEDI. The 3PLs then distributed TEGSEDI to a specialty pharmacy and a specialty distributor, which we collectively refer to as wholesalers, who then distributed TEGSEDI to health care providers and patients. In
    the United States, or U.S., we had a single 3PL as our sole customer and in Canada we also had a single 3PL as our sole customer. Prior to 2021 in Europe, we sold TEGSEDI and WAYLIVRA to hospitals and pharmacies, which were our customers, using 3PLs as
    distributors.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our distribution agreements with Sobi we concluded that our performance obligation is to provide services to Sobi over the term of
    the agreement, which includes supplying finished goods inventory to Sobi. We are also responsible for maintaining the marketing authorization for TEGSEDI and WAYLIVRA in major markets and for leading the global commercial strategy for each medicine. We
    view this performance obligation as a series of distinct activities that are substantially the same. Therefore, we recognize as revenue the price Sobi pays us for the inventory when we deliver the finished goods inventory to Sobi. We also recognize
    distribution fee revenue based on Sobi&#x2019;s net sales of TEGSEDI and WAYLIVRA. Under our agreements with Sobi, Sobi does not generally have a right of return.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Prior to our distribution agreements with Sobi, we recognized TEGSEDI and WAYLIVRA commercial revenue in the period when our customer
    obtained control of our products, which occurred at a point in time upon transfer of title to the customer. We classified payments to customers or other parties in the distribution channel for services that were distinct and priced at fair value as
    selling, general and administrative, or SG&amp;amp;A, expenses in our consolidated statements of operations. We classified payments to customers or other parties in the distribution channel that did not meet those criteria as a reduction of revenue, as
    discussed further below. We excluded from revenues taxes collected from customers relating to TEGSEDI and WAYLIVRA commercial revenue and remitted these amounts to governmental authorities.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Research and development revenue under collaboration agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We enter into collaboration agreements to license and sell our technology on an exclusive or non-exclusive basis. Our collaboration
    agreements typically contain multiple elements, or performance obligations, including technology licenses or options to obtain technology licenses, R&amp;amp;D services and manufacturing services.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We provide details about our collaboration agreements in Note 7, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Collaborative Arrangements and Licensing Agreements&lt;/span&gt;. For each collaboration, we discuss our specific revenue recognition conclusions, including our significant performance obligations under each collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Upfront payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;When we enter into a collaboration agreement and receive an upfront payment, we typically record the entire upfront payment as deferred revenue if our only performance obligation
      is for R&amp;amp;D services we will provide in the future. We amortize the upfront payment into revenue as we perform the R&amp;amp;D services.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Milestone payments:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We include additional consideration in the transaction price when it is probable. We typically include milestone payments for R&amp;amp;D services in the transaction price when they
      are achieved. We include these milestone payments when they are achieved because typically there is considerable uncertainty in the research and development processes that trigger these payments. Similarly, we include approval milestone payments in
      the transaction price once the medicine is approved by the applicable regulatory agency. We will recognize sales-based milestone payments in the period in which we achieve the milestone under the sales-based royalty exception allowed under accounting
      rules.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize milestone payments that relate to an ongoing performance obligation over our period of performance. For example, when
      we achieve a milestone payment from a partner for advancing a clinical study under a collaboration agreement, we add the milestone payment to the transaction price if the milestone relates to an ongoing R&amp;amp;D services performance obligation and
      recognize revenue related to the milestone payment over our estimated period of performance. If we have partially completed our performance obligation, then we record a cumulative-effect adjustment in the period we add the milestone to the
      transaction price.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversely, we recognize in full those milestone payments that we earn based on our partners&#x2019; activities when our partner achieves the
    milestone event and we do not have a performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;License fees:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We generally recognize as revenue the total amount we determine to be the relative stand-alone selling price of a license when we deliver the license to our partner. This is
      because our partner has full use of the license and we do not have any additional performance obligations related to the license after delivery.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;&lt;span style="text-decoration: underline;"&gt;Sublicense fees:&lt;/span&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognize sublicense fee revenue in the period in which a party, who has already licensed our technology, further licenses the technology to another party because we do not
      have any performance obligations related to the sublicense.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Eplontersen Collaboration with AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of transthyretin amyloidosis, or ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the
    U.S., except certain countries in Latin America. Under the terms of the agreement, we received a $200 million upfront payment in 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca are performing, (iii) the co-commercialization activities
    that we and AstraZeneca are performing and (iv) the co-medical affairs activities that we and AstraZeneca are performing.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration and therefore do not have a vendor-customer relationship. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we made an
    accounting policy election to recognize as non-customer revenue the cost-share funding from AstraZeneca, net of our share of AstraZeneca&#x2019;s development expenses, in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we made an accounting policy election to recognize cost-share funding we receive from AstraZeneca
    related to commercial and medical affairs activities as reductions of our SG&amp;amp;A expense and R&amp;amp;D expense, respectively.&lt;/div&gt;
</us-gaap:RevenueFromContractWithCustomerPolicyTextBlock>
    <us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax
      contextRef="c20210101to20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="-6"
      id="Fact_798a2a15b8084859992f963edb75362e"
      unitRef="U001">200000000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
    <ions:NumberOfMaterialComponents
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="INF"
      id="Fact_e051c1fd4e944a92a8163d269956be81"
      unitRef="U005">4</ions:NumberOfMaterialComponents>
    <ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="INF"
      id="Fact_3cba0cc4bb2b4337844e4ffea49760a9"
      unitRef="U006">1</ions:RevenueFromContractWithCustomerNumberOfSeparatePerformanceObligations>
    <ions:RevenueFromContractWithCustomerTransactionPrice
      contextRef="c20211231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="-6"
      id="Fact_37318b29740c484b9341ea66122972eb"
      unitRef="U001">200000000</ions:RevenueFromContractWithCustomerTransactionPrice>
    <ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner
      contextRef="c20220101to20221231_TypeOfArrangementAxis_AstrazenecaCollaborationEplontersenMember"
      decimals="2"
      id="Fact_19aa95d597c248e5a38f0df2e0a747a4"
      unitRef="U003">0.55</ions:PercentageOfCostsAssociatedWithOngoingGlobalPhase3DevelopmentProgramPaidByCollaborationPartner>
    <us-gaap:ReceivablesPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_5725e312987247ee863902943c0938c8">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contracts Receivable&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our contracts receivable balance represents the amounts we
      have billed our partners or customers and that are due to us unconditionally for goods we have delivered or services we have performed. When we bill our partners or customers with payment terms based on the passage of time, we consider the contracts
      receivable to be unconditional. We typically receive payment within one &lt;/span&gt;&lt;span style="-sec-ix-hidden:Fact_e2c2673a057f412ebd5831ca8712546a"&gt;quarter&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; of billing our partner or customer&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022,
    approximately 82.5 percent of our contracts receivables were from one significant customer. As of December 31, 2021, approximately 93.8 percent of our contracts receivables were from two
    significant customers.&lt;/div&gt;
</us-gaap:ReceivablesPolicyTextBlock>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20220101to20221231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_OneSignificantCustomerMember"
      decimals="3"
      id="Fact_8cbaf7e8f6f14ab8b9a5bac9f1a94ee5"
      unitRef="U003">0.825</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20220101to20221231"
      decimals="INF"
      id="Fact_989b31e12c534c2cb51193d15fef47ac"
      unitRef="U007">1</ions:NumberOfSignificantCustomers>
    <us-gaap:ConcentrationRiskPercentage1
      contextRef="c20210101to20211231_ConcentrationRiskByBenchmarkAxis_AccountsReceivableMember_ConcentrationRiskByTypeAxis_CreditConcentrationRiskMember_MajorCustomersAxis_TwoSignificantCustomersMember"
      decimals="3"
      id="Fact_9b60e884ea4946728c18b631acdef31b"
      unitRef="U003">0.938</us-gaap:ConcentrationRiskPercentage1>
    <ions:NumberOfSignificantCustomers
      contextRef="c20210101to20211231"
      decimals="INF"
      id="Fact_5e1263191fc1438492a439c3f8e95b1d"
      unitRef="U007">2</ions:NumberOfSignificantCustomers>
    <us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy
      contextRef="c20220101to20221231"
      id="Text_11c759b68b4b4c4b94628fcf39b9e913">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unbilled SPINRAZA Royalties&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our unbilled SPINRAZA royalties represent our right to receive consideration from Biogen in advance of when we are eligible to bill Biogen
    for SPINRAZA royalties. We include these unbilled amounts in other current assets in our consolidated balance sheets.&lt;/div&gt;
</us-gaap:TradeAndOtherAccountsReceivableUnbilledReceivablesPolicy>
    <us-gaap:RevenueRecognitionPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_4fad649cf4524327bf2658a3254aca30">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: -54pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Deferred Revenue&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We are often entitled to bill our customers and receive
      payment from our customers in advance of our obligation to provide services or transfer goods to our partners. In these instances, we include the amounts in deferred revenue in our consolidated balance sheets.&lt;/span&gt; During the years ended December 31, 2022 and 2021, we recognized $73.5 million and $98.1 million of revenue from
    amounts that were in our beginning deferred revenue balance for each respective period. For further discussion, refer to our revenue recognition policy above.&lt;/div&gt;
</us-gaap:RevenueRecognitionPolicyTextBlock>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_7a9ec3bea8ad464ca6e12c6aa16435cd"
      unitRef="U001">73500000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:ContractWithCustomerLiabilityRevenueRecognized
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_ced6b030f6d146bb91eabbce81e6f413"
      unitRef="U001">98100000</us-gaap:ContractWithCustomerLiabilityRevenueRecognized>
    <us-gaap:CostOfSalesPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_7bb4849d286842ec8c69f3be8efe749c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cost of Sales&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our cost of sales is comprised of costs related to our commercial revenue, including manufacturing costs, transportation and freight costs
    and indirect overhead costs associated with the manufacturing and distribution of our products. We also may include certain period costs related to manufacturing services and inventory adjustments in cost of sales.&lt;/div&gt;
</us-gaap:CostOfSalesPolicyTextBlock>
    <us-gaap:ResearchAndDevelopmentExpensePolicy
      contextRef="c20220101to20221231"
      id="Text_3a1d8d5acce046e6b43dae80c783423c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research, Development and Patent Expenses&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our research, development and patent expenses include wages, benefits, facilities, supplies, external services, clinical trial and
    manufacturing costs, patents and other expenses that are directly related to our research and development operations. We expense research and development costs as we incur them. When we make payments for research and development services prior to the
    services being rendered, we record those amounts as prepaid assets in our consolidated balance sheets and we expense them as the services are provided. A portion of the costs included in research and development expenses are costs associated with our
    partner agreements. In 2022, 2021 and 2020, patent expenses were $4.7 million, $5.3 million and $4.1 million, respectively.&lt;/div&gt;
</us-gaap:ResearchAndDevelopmentExpensePolicy>
    <ions:PatentExpenses
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_85866a721e84472989175bb6188f4c57"
      unitRef="U001">4700000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_a0ff596166e44c50ba79c8d446d1bb4e"
      unitRef="U001">5300000</ions:PatentExpenses>
    <ions:PatentExpenses
      contextRef="c20200101to20201231"
      decimals="-5"
      id="Fact_18be9a3bed5e4b5a815b9ba827f8eb2d"
      unitRef="U001">4100000</ions:PatentExpenses>
    <us-gaap:IncomeTaxPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_2b4437a3b045421c8ee586d057cb332a">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We account for income taxes using the asset and liability method, which requires the recognition of deferred tax assets and liabilities
    for the expected future tax consequences of events that have been recognized in our financial statements or tax returns. In addition, deferred tax assets are recorded for the future benefit of utilizing net operating losses and research and development
    credit carryforwards. We record a valuation allowance when necessary to reduce our net deferred tax assets to the amount expected to be realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We apply the authoritative accounting guidance prescribing a threshold and measurement attribute for the financial recognition and
    measurement of a tax position taken or expected to be taken in a tax return. We recognize liabilities for uncertain tax positions based on a two-step process. The first step is to evaluate the tax position for recognition by determining if the weight
    of available evidence indicates that it is more likely than not that the position will be sustained on audit, including resolution of related appeals or litigation processes, if any. The second step requires us to estimate and measure the tax benefit
    as the largest amount that is more than 50 percent likely to be realized upon ultimate settlement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to use significant judgment in evaluating our uncertain tax positions and determining our provision for income taxes.
    Although we believe our reserves are reasonable, we can provide no assurance that the final tax outcome of these matters will not be different from that which we have reflected in our historical income tax provisions and accruals. We adjust these
    reserves for changing facts and circumstances, such as the closing of a tax audit or the refinement of an estimate. To the extent that the final tax outcome of these matters is different than the amounts recorded, such differences may impact the
    provision for income taxes in the period in which we make such determination.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are also required to use significant judgment in determining any valuation allowance recorded against our deferred tax assets. In
    assessing the need for a valuation allowance, we consider all available evidence, including scheduled reversal of deferred tax liabilities, past operating results, the feasibility of tax planning strategies and estimates of future taxable income. We
    base our estimates of future taxable income on assumptions that are consistent with our plans. The assumptions we use represent our best estimates and involve inherent uncertainties and the application of our judgment. Should actual amounts differ from
    our estimates, the amount of our tax expense and liabilities we recognize could be materially impacted. We record a valuation allowance to reduce the balance of our net deferred tax assets to the amount we believe is more-likely-than-not to be
    realized.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not provide for a U.S. income tax liability and foreign withholding taxes on undistributed foreign earnings of our foreign
    subsidiaries. &lt;/div&gt;
</us-gaap:IncomeTaxPolicyTextBlock>
    <us-gaap:EarningsPerSharePolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_47e97970a2d74b528c3d5e13d3b65bad">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic and Diluted Net Loss per Share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Basic net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We compute basic net loss per share by dividing the total net loss attributable to our common stockholders by our weighted-average number
    of common shares outstanding during the period. For the years ended December 31, 2022 and 2021, we did not have to consider Akcea results separately in our calculation because we owned 100 percent of Akcea for the entire period. Our basic net loss per share for the years ended December 31, 2022 and 2021 was $1.90 and $0.20, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the year ended December 31, 2020, we calculated total net loss attributable to our common stockholders using our net loss for Ionis on
    a stand-alone basis plus our share of Akcea&#x2019;s net loss for the period. To calculate the portion of Akcea&#x2019;s net loss attributable to our ownership, we multiplied Akcea&#x2019;s net loss per share by the weighted average shares we owned in Akcea. As a result of
    this calculation, our total net loss available to Ionis common stockholders for the calculation of net loss per share was different than net loss attributable to Ionis Pharmaceuticals, Inc. common stockholders in our consolidated statements of
    operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(246,702&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(444,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Diluted net loss per share&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022, 2021 and 2020, we incurred a net loss; therefore, we did not include dilutive common equivalent
    shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock underlying the following would have had an anti-dilutive effect on net loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;1%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dilutive stock options;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested restricted stock units, or RSUs;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unvested performance restricted stock units, or PRSUs; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Employee Stock Purchase Plan, or ESPP.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022 and 2021, common stock underlying the following would also have had an anti-dilutive effect on net
    loss per share:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; convertible senior notes, or &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes; and&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Note hedges related to the &lt;/span&gt;0%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Additionally as of December 31, 2022 and 2021, we had warrants related to our 0 percent and 0.125 percent Notes outstanding. We will include the shares issuable
    under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.&lt;/div&gt;
</us-gaap:EarningsPerSharePolicyTextBlock>
    <us-gaap:MinorityInterestOwnershipPercentageByParent
      contextRef="c20221231_OwnershipAxis_AkceaTherapeuticsIncMember"
      decimals="2"
      id="Fact_f65a71d42ef046458f851b185dab48a4"
      unitRef="U003">1</us-gaap:MinorityInterestOwnershipPercentageByParent>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20220101to20221231"
      decimals="2"
      id="Fact_a97fd98180da49a2889ec6c1d1bbecdb"
      unitRef="U004">-1.9</us-gaap:EarningsPerShareBasic>
    <us-gaap:EarningsPerShareBasic
      contextRef="c20210101to20211231"
      decimals="2"
      id="Fact_07af0c67e7e142188bdb734757344850"
      unitRef="U004">-0.2</us-gaap:EarningsPerShareBasic>
    <us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock
      contextRef="c20220101to20221231"
      id="Text_6255ce3fc5024406b256c4e5a5be9dd3">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We calculated our basic net loss per share for the year ended December 31, 2020 as follows (in thousands, except
    per share amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31, 2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Shares&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Owned in Akcea&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Akcea&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;s&lt;/span&gt;&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Basic Net Loss&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per Share&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Calculation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the pre-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;77,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.45&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111,775&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s net loss in the post-merger period attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(85,987&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Akcea&#x2019;s total net loss attributable to our ownership&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(197,762&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ionis&#x2019; stand-alone net loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(246,702&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net loss available to Ionis common stockholders&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(444,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average shares outstanding&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net loss per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3.18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfEarningsPerShareBasicByCommonClassTextBlock>
    <ions:WeightedAverageNumberOfSharesOwnedInSubsidiary
      contextRef="c20200101to20201031_ConsolidatedEntitiesAxis_AkceaTherapeuticsIncMember"
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      unitRef="U002">77095000</ions:WeightedAverageNumberOfSharesOwnedInSubsidiary>
    <us-gaap:EarningsPerShareBasic
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      unitRef="U001">-111775000</us-gaap:NetIncomeLoss>
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      unitRef="U001">-85987000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
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      id="Fact_309e78e4285341cca5cecc72425624ab"
      unitRef="U001">-197762000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLoss
      contextRef="c20200101to20201231_StatementBusinessSegmentsAxis_IonisCoreMember"
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      id="Fact_ca9bbb6fa2d6476682237132e18e3ea3"
      unitRef="U001">-246702000</us-gaap:NetIncomeLoss>
    <us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic
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      id="Fact_129a4e0e3dab487eb3bebb6a384cf36a"
      unitRef="U001">-444464000</us-gaap:NetIncomeLossAvailableToCommonStockholdersBasic>
    <us-gaap:WeightedAverageNumberOfSharesOutstandingBasic
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      unitRef="U002">139612000</us-gaap:WeightedAverageNumberOfSharesOutstandingBasic>
    <us-gaap:EarningsPerShareBasic
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      id="Fact_885ea3503dd64edf8316c0c40aa93e87"
      unitRef="U004">-3.18</us-gaap:EarningsPerShareBasic>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-Based Compensation Expense&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock
    purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service
    period in our consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated
    multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award
    were in substance multiple awards, which results in the expense being front-loaded over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Stock Options and Stock Purchase Rights:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant
    date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the
    awards, and actual and projected employee stock option exercise behaviors. The expected term of stock options granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options granted
    based on historical exercise patterns. In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options
    granted under these plans from seven years to ten years for stock options granted on January 1, 2022 and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this
    change because the contractual term changed and we have no other means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended
    December 31, 2022. Under the simplified method, we calculate the expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected
    term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;RSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest
    annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. RSUs granted to our board of directors after June 2020 fully vest after one year.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PRSU&#x2019;s:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. Beginning in 2022, we added
    PRSU awards to the compensation for our other Section 16 officers. Under the terms of the grants, &lt;span style="-sec-ix-hidden:Fact_65d15117ab79462e81dfb8bbb86a0107"&gt;&lt;span style="-sec-ix-hidden:Fact_e9934b85c6af480197be8d0d8b5ea434"&gt;&lt;span style="-sec-ix-hidden:Fact_5599af32346c4fce91fa6d27caf4b474"&gt;one third&lt;/span&gt;&lt;/span&gt;&lt;/span&gt; of the PRSUs may vest at the end
    of three separate performance periods spread over the three years following the date of grant (i.e., the one-year period commencing on the
    date of grant and ending on the first anniversary of the date of grant; the two-year period commencing on the date of grant and ending on the
    second anniversary of the date of grant; and the three-year period commencing on the date of grant and ending on the third anniversary of the
    date of grant) based on our relative total shareholder return, or TSR, as compared to a peer group of companies, and as measured, in each case, at the end of the applicable performance period. Under the terms of the grants no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 150 percent of the target number
    depending on our relative TSR.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which
    represents a market condition. We are recognizing the grant date fair value of these awards as stock-based compensation expense using the accelerated multiple-option approach over the vesting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Part IV, Item 15, Note 5, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Stockholders&#x2019;
      Equity,&lt;/span&gt; for additional information regarding our stock-based compensation plans.&lt;/div&gt;
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    <us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Noncontrolling Interest in Akcea Therapeutics, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Since Akcea&#x2019;s IPO in July 2017 and prior to the Akcea Merger
      in October 2020, the shares of Akcea&#x2019;s common stock third parties owned represented an interest in Akcea&#x2019;s equity that we did not control. During this period our ownership ranged from &lt;/span&gt;68 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;77 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. However, as we maintained overall control of Akcea through our voting interest, we reflected the assets, liabilities and results of operations of
      Akcea in our consolidated financial statements. Since Akcea&#x2019;s IPO in July 2017 and through the closing of the Akcea Merger, we reflected the noncontrolling interest attributable to other owners of Akcea&#x2019;s common stock on a separate line in our
      statements of operations and a separate line within stockholders&#x2019; equity in our consolidated balance sheets. In addition, through the closing of the Akcea Merger, we recorded a noncontrolling interest adjustment to account for the stock options Akcea
      granted, which if exercised, would have diluted our ownership in Akcea. This adjustment was a reclassification within stockholders&#x2019; equity from additional paid-in capital to noncontrolling interest in Akcea equal to the amount of stock-based
      compensation expense Akcea had recognized. Additionally, w&lt;/span&gt;e reflected changes in our ownership percentage in our financial statements as an adjustment to noncontrolling interest in the period the change occurred.&lt;/div&gt;
</us-gaap:ConsolidationSubsidiariesOrOtherInvestmentsConsolidatedEntitiesPolicy>
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Accumulated Other Comprehensive Loss&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,395&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,486&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(417&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive income (losses) for the year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,812&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,597&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(57,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;div&gt;
    &lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; text-align: right;"&gt;
            &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;
          &lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top;"&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;&lt;/div&gt;
          &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
    &lt;/div&gt;
</us-gaap:StockholdersEquityPolicyTextBlock>
    <us-gaap:ScheduleOfAccumulatedOtherComprehensiveIncomeLossTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_ec1d7d26eac54b93a442dd102450e116">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Accumulated other
      comprehensive loss is comprised of unrealized gains and losses on investments, net of taxes and currency translation adjustments. The following table summarizes changes in accumulated other comprehensive loss for the years ended December 31, 2022, 2021 and 2020 (in thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div style="text-align: justify;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; &lt;/span&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(25,290&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unrealized gains (losses) on securities, net of tax (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,395&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,486&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Currency translation adjustment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(417&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;617&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Adjustments to other comprehensive loss from purchase of noncontrolling interest of Akcea Therapeutics, Inc.&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(127&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net other comprehensive income (losses) for the year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,812&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,597&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,219&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance accumulated other comprehensive loss&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(57,480&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,668&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(21,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;div&gt;
    &lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; text-align: right;"&gt;
            &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/div&gt;
          &lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top;"&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have tax expense included in our other comprehensive loss for the years ended December 31, 2022, 2021 and 2020.&#160;&lt;/div&gt;
          &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
    &lt;/div&gt;
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      decimals="-3"
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      contextRef="c20211231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember"
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    <us-gaap:StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest
      contextRef="c20201231_StatementEquityComponentsAxis_AociIncludingPortionAttributableToNoncontrollingInterestMember"
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    <us-gaap:OtherComprehensiveIncomeLossTax
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    <us-gaap:OtherComprehensiveIncomeLossTax
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    <us-gaap:ConcentrationRiskCreditRisk
      contextRef="c20220101to20221231"
      id="Text_2657526565084c29a44990225a255af0">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Concentration of Credit Risk&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Financial instruments that potentially subject us to concentrations of credit risk consist primarily of cash equivalents, short-term
    investments and receivables. We place our cash equivalents and short-term investments with reputable financial institutions. We primarily invest our excess cash in commercial paper and debt instruments of the U.S. Treasury, financial institutions,
    corporations, and U.S. government agencies with strong credit ratings and an investment grade rating at or above A-1, P-1 or F-1 by Moody&#x2019;s, Standard &amp;amp; Poor&#x2019;s, or S&amp;amp;P, or Fitch, respectively. We have established guidelines relative to
    diversification and maturities that maintain safety and liquidity. We periodically review and modify these guidelines to maximize trends in yields and interest rates without compromising safety and liquidity.&lt;/div&gt;
</us-gaap:ConcentrationRiskCreditRisk>
    <us-gaap:FairValueOfFinancialInstrumentsPolicy
      contextRef="c20220101to20221231"
      id="Text_1c1a3fa5b06c4f8eb0d08a8a2d8e1c26">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have estimated the fair value of our financial instruments. The amounts reported for cash, accounts receivable, accounts payable and
    accrued expenses approximate the fair value because of their short maturities. We report our investment securities at their estimated fair value based on quoted market prices for identical or similar instruments.&lt;/div&gt;
</us-gaap:FairValueOfFinancialInstrumentsPolicy>
    <us-gaap:InvestmentPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_6331a27b92f04118a22313343e337534">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Cash, Cash Equivalents and Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We consider all liquid investments with maturities of three months or less when we purchase them to be cash equivalents. Our short-term
    investments have initial maturities of greater than three months from date of purchase. We classify our short-term debt investments as &#x201c;available-for-sale&#x201d; and carry them at fair market value based upon prices on the last day of the fiscal period for
    identical or similar items. We record unrealized gains and losses on debt securities as a separate component of comprehensive income (loss) and include net realized gains and losses in gain (loss) on investments in our consolidated statements of
    operations. We use the specific identification method to determine the cost of securities sold.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also have equity investments of less than 20 percent ownership in publicly and privately held biotechnology companies that we
      received as part of a technology license or partner agreement. At December 31, 2022, we held equity investments in three publicly traded companies and eight
      privately held companies.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are required to measure and record our equity investments at fair value and to recognize the changes in fair value in our consolidated
    statements of operations. We account for our equity investments in privately held companies at their cost minus impairments, plus or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment
    of the same issuer.&lt;/div&gt;
</us-gaap:InvestmentPolicyTextBlock>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20221231"
      decimals="INF"
      id="Fact_b448547c88c7434cbc329f97a4b3ea28"
      unitRef="U009">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20221231"
      decimals="INF"
      id="Fact_5091e6339b9e4e85943dd42b9d332383"
      unitRef="U009">8</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:InventoryPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_962b0a89596444369c91918399edde59">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Inventories&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We reflect our inventory in our consolidated balance sheets at the lower of cost or net realizable value under the first-in, first-out
    method, or FIFO. We capitalize the costs of raw materials that we purchase for use in producing our medicines because until we use these raw materials, they have alternative future uses, which we refer to as clinical raw materials. We include in
    inventory raw material costs for medicines that we manufacture for our partners under contractual terms and that we use primarily in our clinical development activities and drug products. We can use each of our raw materials in multiple products and,
    as a result, each raw material has future economic value independent of the development status of any single medicine. For example, if one of our medicines failed, we could use the raw materials for that medicine to manufacture our other medicines. We
    expense these costs as R&amp;amp;D expenses when we begin to manufacture API for a particular medicine if the medicine has not been approved for marketing by a regulatory agency. Our raw materials- commercial inventory includes API for our commercial
    medicines. We capitalize material, labor and overhead costs as part of our raw materials- commercial inventory.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We review our inventory periodically and reduce the carrying value of items we consider to be slow moving or obsolete to their estimated
    net realizable value based on forecasted demand compared to quantities on hand. We consider several factors in estimating the net realizable value, including shelf life of our inventory, alternative uses for our medicines in development and historical
    write-offs.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,061&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,699&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,760&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,109&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;164&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,033&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:InventoryPolicyTextBlock>
    <us-gaap:ScheduleOfInventoryCurrentTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_42918dc083b14298bf3e140fca4a1e1b">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our inventory consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 19.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- clinical&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,061&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,507&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -18pt; margin-left: 28.4pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Raw materials- commercial&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,699&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,139&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total raw materials&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19,760&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,646&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Work in process&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,109&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Finished goods&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;164&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;390&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 28.45pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total inventory&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,033&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24,806&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfInventoryCurrentTableTextBlock>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_607597dd540146e09e590486dfbfd332"
      unitRef="U001">17061000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231_PublicUtilitiesInventoryAxis_ClinicalRawMaterialsMember"
      decimals="-3"
      id="Fact_7cb2d5b100c4460fa603ceb958dfa363"
      unitRef="U001">14507000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_7ce8ae9ab80f4c6b893833f04a2e1b3a"
      unitRef="U001">2699000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231_PublicUtilitiesInventoryAxis_CommercialRawMaterialsMember"
      decimals="-3"
      id="Fact_de29fe59994e4eedaaf0e505fe2fa8ce"
      unitRef="U001">4139000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20221231"
      decimals="-3"
      id="Fact_128d62d036e2429290b412a68bb359e3"
      unitRef="U001">19760000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryRawMaterials
      contextRef="c20211231"
      decimals="-3"
      id="Fact_2a47aa942a2943ed97036570c8b25890"
      unitRef="U001">18646000</us-gaap:InventoryRawMaterials>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20221231"
      decimals="-3"
      id="Fact_85d7f4970a574d26939ed8575266e7f1"
      unitRef="U001">2109000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryWorkInProcess
      contextRef="c20211231"
      decimals="-3"
      id="Fact_84044948dea84b95bf0906aa87b24ba3"
      unitRef="U001">5770000</us-gaap:InventoryWorkInProcess>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20221231"
      decimals="-3"
      id="Fact_e5ad76dbdb1441b68871a7035a59c0b3"
      unitRef="U001">164000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryFinishedGoods
      contextRef="c20211231"
      decimals="-3"
      id="Fact_518f7488f3314fafb99fe4a5c96254f0"
      unitRef="U001">390000</us-gaap:InventoryFinishedGoods>
    <us-gaap:InventoryNet
      contextRef="c20221231"
      decimals="-3"
      id="Fact_ed1f9a6ae98d4c7cba25f90cb15577f3"
      unitRef="U001">22033000</us-gaap:InventoryNet>
    <us-gaap:InventoryNet
      contextRef="c20211231"
      decimals="-3"
      id="Fact_d2b4370b0072452b9c9faa8459b51794"
      unitRef="U001">24806000</us-gaap:InventoryNet>
    <us-gaap:PropertyPlantAndEquipmentPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_cdabff15346b44629390c82abd47c849">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Property, Plant and Equipment&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated Useful&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Lives (in years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,351&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,802&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,158&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,046&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;-&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,077&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,357&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,144&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,575&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;153,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;257,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(102,653&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;155,007&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,294&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,069&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we sold the facilities and related land at our headquarters for net proceeds of $202.6 million in connection with a sale and leaseback transaction.&#160; In connection with the sale of these real estate assets, we de-recognized the related land and improvements,
    building and building improvements, which resulted in a net gain of $150.1 million that we reported in other income (expense) in our consolidated
    statements of operations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We depreciate our leasehold improvements using the shorter of the estimated useful life or remaining lease term. We evaluate long-lived
    assets, which include property, plant and equipment, for impairment on at least a quarterly basis and whenever events or changes in circumstances indicate that we may not be able to recover the carrying amount of such assets.&lt;/div&gt;
</us-gaap:PropertyPlantAndEquipmentPolicyTextBlock>
    <us-gaap:PropertyPlantAndEquipmentTextBlock
      contextRef="c20220101to20221231"
      id="Text_fa1490903d3d4bf4a66e00ec0646e2ed">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We carry our property, plant and equipment at cost and depreciate it on the straight-line method over its
    estimated useful life, which consists of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated Useful&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Lives (in years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Computer software, laboratory, manufacturing and other equipment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,351&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,802&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Building, building improvements and building systems&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15 to 40&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;41,158&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;144,046&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;-&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,077&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Leasehold improvements&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 15&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28,357&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,144&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Furniture and fixtures&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5 to 10&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,575&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,591&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;153,441&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;257,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less accumulated depreciation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(87,716&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(102,653&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;155,007&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Land&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,569&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,062&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#160;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,294&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,069&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our accrued liabilities consisted of the following (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Clinical expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;116,460&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;65,730&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In-licensing expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,945&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,044&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Commercial expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,498&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,471&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -18pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other miscellaneous expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,198&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,315&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total accrued liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;140,101&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88,560&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfAccruedLiabilitiesTableTextBlock>
    <ions:AccruedClinicalExpenses
      contextRef="c20221231"
      decimals="-3"
      id="Fact_dd19e9b42ea648b5a66ad1c40729f204"
      unitRef="U001">116460000</ions:AccruedClinicalExpenses>
    <ions:AccruedClinicalExpenses
      contextRef="c20211231"
      decimals="-3"
      id="Fact_fac7f03b039f4f02a05228c036fc1f3c"
      unitRef="U001">65730000</ions:AccruedClinicalExpenses>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_4a54e14632b04a9cb08ecbd7c4f7b264"
      unitRef="U001">7945000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedInLicensingFeesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_a1182bff6aa841d1b17861b49376378a"
      unitRef="U001">8044000</ions:AccruedInLicensingFeesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_991e082179bb4e87b5afb60cdf56fada"
      unitRef="U001">3498000</ions:AccruedCommercialExpensesCurrent>
    <ions:AccruedCommercialExpensesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_dce6ebe7c0d64208a814a92b3849fcba"
      unitRef="U001">2471000</ions:AccruedCommercialExpensesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_36801832e43e415bbc066744d39ceba6"
      unitRef="U001">12198000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:OtherAccruedLiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_558a2514ca9d46d38ef6431a99ec3875"
      unitRef="U001">12315000</us-gaap:OtherAccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20221231"
      decimals="-3"
      id="Fact_d3d4336195b54976b7bcea8d3b30b7ac"
      unitRef="U001">140101000</us-gaap:AccruedLiabilitiesCurrent>
    <us-gaap:AccruedLiabilitiesCurrent
      contextRef="c20211231"
      decimals="-3"
      id="Fact_e91e73e81dd74acab89c06a66144eab3"
      unitRef="U001">88560000</us-gaap:AccruedLiabilitiesCurrent>
    <ions:LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_3eb4a04acef14a91ad67a265cb0fcc2c">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Estimated Liability for Clinical Development Costs&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have numerous medicines in preclinical studies and/or clinical trials at clinical sites throughout the world. On at least a quarterly
    basis, we estimate our liability for preclinical and clinical development costs we have incurred and services that we have received but for which we have not yet been billed and maintain an accrual to cover these costs. These costs primarily relate to
    third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator grants. We estimate our liability using assumptions about study and patient activities and the related expected expenses for those activities
    determined based on the contracted fees with our service providers. The assumptions we use represent our best estimates of the activity and expenses at the time of our accrual and involve inherent uncertainties and the application of our judgment. Upon
    settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual amounts.&lt;/div&gt;
</ions:LiabilityForClinicalDevelopmentCostsPolicyPolicyTextBlock>
    <us-gaap:DebtPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_30f2fdb1a267491fb1834b1b077b624c">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We account for each of our convertible debt instruments as a
      single unit of accounting, a liability, because we concluded that the conversion features do not require bifurcation as a derivative under ASC 815-15 and we did not issue our convertible debt instruments at a substantial premium. We record debt
      issuance costs as contra-liabilities in our consolidated balance sheets at issuance and amortize them over the contractual term of the convertible debt instrument using the effective interest rate. &lt;/span&gt;The&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; balances of our convertible senior notes presented in our consolidated balance sheets represent the principal balance of each convertible debt instrument less debt issuance costs.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022, we had two
    outstanding convertible senior notes, our 0% Notes, which mature in April 2026, and our 0.125% Notes, which mature in December 2024. Refer to Part IV, Item 15, Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term
      Obligations and Commitments&lt;/span&gt;, for further details on our convertible senior notes.&lt;/div&gt;
</us-gaap:DebtPolicyTextBlock>
    <ions:DebtInstrumentNumberOfConvertibleNotes
      contextRef="c20221231"
      decimals="INF"
      id="Fact_10f5114021fc4f5bb04196fe30354c8a"
      unitRef="U010">2</ions:DebtInstrumentNumberOfConvertibleNotes>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_88cf15606ae648ba879a91ce9224095e"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_637081ace1c3467395b29f412ee7c215"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DerivativesPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_aa6c21ff1d40469fbb64ee19c123e452">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the issuance of our 0%
    Notes and 0.125% Notes in April 2021 and December 2019, respectively, we entered into call spread transactions, which were comprised of
    purchasing note hedges and selling warrants. We account for the note hedges and warrants as separate freestanding financial instruments and treat each instrument as a separate unit of accounting. We determined that the note hedges and warrants do not
    meet the definition of a liability using the guidance contained in ASC Topic 480; therefore, we account for the note hedges and warrants using the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Derivatives
      and Hedging &#x2013; Contracts in Entity&#x2019;s Own Equity&lt;/span&gt; accounting guidance contained in ASC Topic 815. We determined that the note hedges and warrants meet the definition of a derivative, are indexed to our stock and meet the criteria to be classified
    in shareholders&#x2019; equity. We recorded the aggregate amount paid for the note hedges and the aggregate amount received for the warrants as additional paid-in capital in our consolidated balance sheets. We reassess our ability to continue to classify the
    note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;
</us-gaap:DerivativesPolicyTextBlock>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_fe2e410b891c4e8f90e9c7af0b2fd97c"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_ad09e792f7534196a47d6e0a5fba48da"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:LesseeLeasesPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_5a1cbe260fe343ccafe9ff400e9af2db">
&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determine if an arrangement contains a lease at inception. We currently only have operating leases. We recognize a right-of-use
    operating lease asset and associated short- and long-term operating lease liability in our consolidated balance sheets for operating leases greater than one year. Our right-of-use assets represent our right to use an underlying asset for the lease term
    and our lease liabilities represent our obligation to make lease payments arising from the lease arrangement. We recognize our right-of-use operating lease assets and lease liabilities based on the present value of the future minimum lease payments we
    will pay over the lease term.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;&#160;&lt;/span&gt;We determine the lease term at the inception of each lease, and in certain cases our lease term could include renewal
    options if we conclude we are reasonably certain to exercise the renewal option. When we exercise a lease option that was not previously included in the initial lease term, we reassess our right-of-use asset and lease liabilities for the new lease
    term.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As our leases do not provide an interest rate implicit in the lease, we use our incremental borrowing rate, based on the information
    available as of the lease inception date or at the lease option extension date in determining the present value of future payments. We recognize rent expense for our minimum lease payments on a straight-line basis over the expected term of our lease.
    Our leases do not include material variable or contingent lease payments. We recognize period expenses, such as common area maintenance expenses, in the period we incur the expense.&lt;/div&gt;
</us-gaap:LesseeLeasesPolicyTextBlock>
    <us-gaap:SegmentReportingPolicyPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_281d2bc17d7c4cccaa098d6476ac69ff">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Segment Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In 2021, we began operating as a single segment, Ionis operations, because our chief decision maker reviews operating results on an
    aggregate basis and manages our operations as a &lt;span style="-sec-ix-hidden:Fact_33bc30118e9548358994c912eadf2161"&gt;single&lt;/span&gt; operating segment. Previously, we had operated as two operating segments, Ionis Core and Akcea Therapeutics. We completed the Akcea Merger in October 2020 and fully integrated Akcea&#x2019;s operations into ours as of January 1, 2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;
</us-gaap:SegmentReportingPolicyPolicyTextBlock>
    <us-gaap:NumberOfOperatingSegments
      contextRef="c20200101to20201231"
      decimals="INF"
      id="Fact_a315f651d2c042c59a48e5688cd8c8d7"
      unitRef="U011">2</us-gaap:NumberOfOperatingSegments>
    <us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock
      contextRef="c20220101to20221231"
      id="Text_702601a4d67748f5a98dd7344990b6c7">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Recently Adopted Accounting Standards&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2022, the Financial Accounting Standards Board, or FASB, issued clarifying guidance on fair value measurement of equity securities
    subject to contractual trading restrictions. The guidance clarifies that contractual trading restrictions are not considered part of the unit of account of equity securities and therefore, are not considered when measuring the fair value of equity
    securities. This update is effective for interim and annual periods beginning January 1, 2024 on a prospective basis. Early adoption of this guidance is permitted at an interim or annual period. We early adopted this new guidance in the third quarter
    of 2022. This guidance did not have a material impact on our consolidated financial statements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not expect any other recently issued accounting standards to have a material impact to our financial results.&lt;/div&gt;
</us-gaap:NewAccountingPronouncementsPolicyPolicyTextBlock>
    <us-gaap:InvestmentTextBlock
      contextRef="c20220101to20221231"
      id="Text_9571e0c61df44815a452af9dc71349ef">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2. Investments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2022:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt;
            or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As illustrated above, at December 31, 2022,
    98 percent of our available-for-sale securities had a maturity of less than two years.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;All of our available-for-sale securities are available to us for use in our current operations. As a result, we categorize all of these
    securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At December 31, 2022, we had an ownership interest of less than 20 percent &lt;/span&gt;in eight
    privately held companies and three publicly held companies with which we conduct business&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,790&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,365&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;509,448&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133,585&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,829&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;131,756&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;512,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;507,554&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,484&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,816&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,008&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,223,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,018&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,211,568&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;227,631&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;217,502&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,339&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,040&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,109&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;240,921&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;116&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(329&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,101&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;525,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(15,621&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;509,823&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,748,836&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27,639&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,721,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,911&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,783,848&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,451&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,997&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,772,302&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,778&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,248,124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,852&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,527&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash
            equivalents in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $7.7 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized
              non-cash loss in our consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.&lt;/span&gt;&#160;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus
            or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in our consolidated balance
              sheets.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we considered to be
      temporarily impaired at&#160;&lt;/span&gt;December 31, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands).
      All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more
      likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,136&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,629&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;305,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,879&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;689,503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93,862&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(538&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,331&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;164,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,869&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;616,826&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,082&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,325&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;703,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,117&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(225&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,465&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(790&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,582&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,015&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,112,941&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;499,383&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,165&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,612,324&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27,639&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:InvestmentTextBlock>
    <us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_df6d78f5b0db4f2293f255a3abc4674a">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the contract maturity of the available-for-sale securities we held as of December 31, 2022:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;One year&lt;/span&gt;
            or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;one year&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;After &lt;span style="text-indent: 0pt;"&gt;two years&lt;/span&gt;
            but within &lt;span style="text-indent: 0pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_5b50da2d62974df399b2ebfcfccf0c30"&gt;three and a half years&lt;/span&gt;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:InvestmentsClassifiedByContractualMaturityDateTableTextBlock>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20220101to20221231"
      id="Fact_a0389bbbc04d444aa9945a16f2f77b47">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage
      contextRef="c20221231"
      decimals="2"
      id="Fact_e1a84f7ba1234915827448c633c10e96"
      unitRef="U003">0.70</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearPercentage>
    <ions:MaximumContractMaturityPeriodRange1
      contextRef="c20220101to20221231"
      id="Fact_a9a809b245674eb5912c14df728dc0f0">P1Y</ions:MaximumContractMaturityPeriodRange1>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20221231"
      id="Fact_d1dd3aa1c3444cc8babea1f02c42cb74">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage
      contextRef="c20221231"
      decimals="2"
      id="Fact_54f16a3082454b16a1368f8660393627"
      unitRef="U003">0.28</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20221231"
      id="Fact_649df9025a904bcfad6dc6ab6bd4c304">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage
      contextRef="c20221231"
      decimals="2"
      id="Fact_d60e9c8e586b428c886b9d9653ac0f6e"
      unitRef="U003">0.02</ions:AvailableForSaleSecuritiesDebtMaturitiesAfterTwoThroughThreeAndOneHalfYearsPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage
      contextRef="c20221231"
      decimals="2"
      id="Fact_298fc5ad20a2442399af2cd8e8215ece"
      unitRef="U003">1</ions:AvailableForSaleSecuritiesDebtMaturitiesTotalPercentage>
    <ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage
      contextRef="c20221231"
      decimals="2"
      id="Fact_971b070bcf6846b8970847cdbaef1457"
      unitRef="U003">0.98</ions:AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage>
    <ions:MaximumContractMaturityPeriodRange2
      contextRef="c20220101to20221231"
      id="Fact_e4aa3be8fcd040d0bcd0def824af337d">P2Y</ions:MaximumContractMaturityPeriodRange2>
    <ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20221231"
      decimals="INF"
      id="Fact_c487d989afb240aaae9be0536d4b8656"
      unitRef="U009">8</ions:NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment>
    <ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment
      contextRef="c20221231"
      decimals="INF"
      id="Fact_cc8fa179d30548a7b52fcdc75fe7eeee"
      unitRef="U009">3</ions:NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment>
    <us-gaap:UnrealizedGainLossOnInvestmentsTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_8334d44cad3443a9ab4f38e658200dff">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following is a summary of our investments (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;513,790&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,365&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;509,448&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;133,585&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,829&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;131,756&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;512,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;507,554&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57,484&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,816&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,008&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,223,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(12,018&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,211,568&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;227,631&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(10,143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;217,502&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,339&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,040&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;33,299&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;245,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,109&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;240,921&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;116&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(329&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,101&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;525,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;130&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(15,621&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;509,823&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,748,836&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;194&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27,639&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,721,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;40,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;35,012&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,257&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,358&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,911&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,783,848&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,451&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,997&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,772,302&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amortized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gross Unrealized&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt; Cost&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Gains&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Available-for-sale securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;383,870&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(226&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,372&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;19&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48,494&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,424&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(64&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,360&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,770&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;134,778&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of one year or less&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;612,557&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;792&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(345&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;613,004&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;382,000&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;331&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,644&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;379,687&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,935&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(561&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;72,374&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;139&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(500&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;137,274&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,909&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(224&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;39,686&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,136&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total securities with a maturity of more than one year&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;638,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;471&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,966&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;635,120&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,172&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,311&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,248,124&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Equity securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in other current assets (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,897&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,145&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities included in deposits and other assets (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,615&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16,707&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,322&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;27,512&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;23,852&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #FFFFFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50,527&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #FFFFFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total available-for-sale and equity securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,278,684&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25,115&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,298,651&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Includes investments classified as cash
            equivalents in our consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our equity securities included in other current
            assets consisted of our investments in publicly traded companies. We recognize publicly traded equity securities at fair value. In the year ended December 31, 2022, we recognized a $7.7 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;unrealized
              non-cash loss in our consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.&lt;/span&gt;&#160;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our equity securities included in deposits and other assets consisted of our investments in privately held companies. We recognize our private company equity securities at&lt;/span&gt; cost minus impairments, plus
            or minus changes resulting from observable price changes in orderly transactions for the identical or similar investment of the same issuer&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in our consolidated balance
              sheets.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The following is a summary of our investments we considered to be
      temporarily impaired at&#160;&lt;/span&gt;December 31, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;(in thousands).
      All of these investments have less than 12 months of temporary impairment. We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase. We believe it is more
      likely than not that we will be able to hold our debt securities to maturity. Therefore, we anticipate full recovery of our debt securities&#x2019; amortized cost basis at maturity.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;

        &lt;/td&gt;

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    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Less than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;More than 12 Months of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Temporary Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Total Temporary&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Impairment&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number of&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Investments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Estimated&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Fair Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unrealized&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Losses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;384,136&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,629&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;305,367&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(11,879&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;689,503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;93,862&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(538&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;70,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,331&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;164,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2,869&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;616,826&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,082&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,325&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;703,151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;110&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,117&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(225&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31,465&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(790&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49,582&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,015&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,993&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 16%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total temporarily impaired securities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,112,941&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9,474&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;499,383&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,165&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,612,324&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(27,639&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfTemporaryImpairmentLossesInvestmentsTableTextBlock>
    <us-gaap:DebtSecuritiesAvailableForSaleContinuousUnrealizedLossPositionLessThan12MonthsNumberOfPositions
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    <us-gaap:FairValueDisclosuresTextBlock
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;3. Fair Value Measurements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We use a three-tier fair value hierarchy to prioritize the inputs used in our fair value measurements. These tiers include: Level 1,
    defined as observable inputs such as quoted prices in active markets for identical assets, which includes our money market funds and treasury securities classified as available-for-sale securities and our investment in equity securities in publicly
    traded biotechnology companies; Level 2, defined as inputs other than quoted prices in active markets that are either directly or indirectly observable, which includes our fixed income securities and commercial paper classified as available-for-sale
    securities; and Level 3, defined as unobservable inputs in which little or no market data exists, therefore requiring us to develop our own assumptions. We classify most of our securities as Level 2. We obtain the fair value of our Level 2 investments
    from our custodian bank or from a professional pricing service. We validate the fair value of our Level 2 investments by understanding the pricing model used by the custodian banks or professional pricing service provider and comparing that fair value
    to the fair value based on observable market prices.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2022 and 2021&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;that we regularly measure and carry at fair value&lt;/span&gt;. As of December 31, 2022, we did not have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy
    of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;726,950&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;726,950&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;165,055&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;165,055&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;748,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;748,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,917&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,917&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,943,585&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;970,669&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;972,916&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our
            consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$11.0 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets in our
            consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Convertible Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our 0.125% Notes and 0% Notes had a fair value of $498.9 million and $587.3 million at December 31, 2022,
    respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.&lt;/div&gt;
</us-gaap:FairValueDisclosuresTextBlock>
    <us-gaap:FairValueAssetsMeasuredOnRecurringBasisTextBlock
      contextRef="c20220101to20221231"
      id="Text_7c9a839c17e4425f94cd5f5cc03bd076">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following tables present the major security types we held at December 31, 2022 and 2021&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;that we regularly measure and carry at fair value&lt;/span&gt;. As of December 31, 2022, we did not have any investments that we valued using Level 3 inputs. The following tables segregate each security type by the level within the fair value hierarchy
    of the valuation techniques we utilized to determine the respective securities&#x2019; fair value (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;211,655&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;726,950&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;726,950&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;165,055&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;165,055&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;748,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;748,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,917&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;74,917&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,994&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,539&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,943,585&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;970,669&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;972,916&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Quoted Prices in&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Active Markets&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant Other&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Observable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Significant&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Unobservable Inputs&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Level 3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cash equivalents (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;541,199&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Corporate debt securities (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;764,059&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by U.S. government agencies (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,868&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by the U.S. Treasury (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;182,634&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Debt securities issued by states of the U.S. and political subdivisions of the states (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;174,464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other municipal debt securities (2)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,099&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div&gt;
            &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Publicly traded equity securities included in other current assets (4)&lt;/div&gt;
          &lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;18,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,875&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -8.9pt; margin-left: 22.55pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,807,528&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;727,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in cash and cash equivalents in our
            consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in short-term investments.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$11.0 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in other current assets in our
            consolidated balance sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$2.3 million included in cash and cash equivalents in our consolidated balance sheets, with the difference included in short-term investments in our consolidated balance
            sheets.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;4. Long-Term Obligations and Commitments&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The carrying value of our long-term obligations was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0 percent&lt;/span&gt;
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;622,242&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619,119&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0.125 percent&lt;/span&gt;
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;544,504&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;186,156&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,058&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Mortgage debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60,054&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,295&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,369,195&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,050&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: current portion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,535&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,526&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total Long-Term Obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,361,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,247,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Convertible Debt and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0 Percent
    Convertible Senior Notes and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we completed a $632.5
    million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022,
    we had the following 0% Notes outstanding (in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_ca0956ae2da341f1b584cfebcf6fbda4"&gt;April 2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and
    selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% Notes by increasing the effective conversion
    price on our 0% Notes. We increased our effective conversion price to $76.39 with the same number of underlying shares as our 0% Notes. The call spread cost
    us $46.9 million, of which $136.7
    million was for the note hedge purchase, offset by $89.8 million we received for selling the warrants. Similar to our 0% Notes, our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the 0% Notes. The note hedges will expire upon maturity of the 0%
    Notes, or April 2026. The note hedges and warrants are separate transactions and are not part of the terms of our 0% Notes. The holders of the 0% Notes do not have any rights with respect to the note hedges and warrants.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;0.125 Percent
    Convertible Senior Notes and Call Spread&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2019, we entered into privately negotiated exchange and/or subscription agreements with certain new investors and certain
    holders of our existing 1% Notes to exchange $375.6
    million of our 1% Notes for $439.3
    million of our 0.125% Notes, and to issue $109.5
    million of our 0.125% Notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022,
    we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_823fe367bb0d42249b87ea8d290aa62a"&gt;December 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In conjunction with the issuance of our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes in December 2019, we entered into a call spread transaction, which
      was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our &lt;/span&gt;0.125%
    Notes by increasing the effective conversion price on our 0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. We increased our effective conversion price to $&lt;/span&gt;123.38&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; with the same number of underlying shares as our &lt;/span&gt;0.125%&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; Notes. The call spread cost us $&lt;/span&gt;52.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, of
      which $&lt;/span&gt;108.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million was for the note hedge purchase,
      offset by $&lt;/span&gt;56.1&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million we received for selling the
      warrants. Similar to our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, our note hedges are
      subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The note hedges will expire upon maturity of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. The holders of the &lt;/span&gt;0.125% Notes&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; do not have any rights with respect to the note hedges and warrants.&lt;/span&gt;&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our
    consolidated balance sheets. Refer to Part IV, Item 15, Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Significant Accounting Policies&lt;/span&gt;, for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders&#x2019; equity at each reporting period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1 Percent
    Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2021, we repurchased $247.9
    million in aggregate principal amount of our 1% Notes in privately negotiated transactions. As a result of the repurchase, we recognized an $8.6 million loss on early retirement of debt in the second quarter of 2021, reflecting the early retirement of a significant portion of our 1% Notes. The loss on the early retirement of our debt is the difference between the amount paid to retire our 1% Notes and the net carrying balance of the liability at the time that we retired the debt. We paid the remaining principal balance of our 1% Notes with $62.0 million of cash at maturity in November 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Other Terms of Convertible Senior Notes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The 0% and 0.125% Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash,
    shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of
    certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to 100 percent of the principal
    amount of the notes to be purchased, plus any accrued and unpaid interest. The 1% Notes were subject to similar terms.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our total interest expense for our outstanding senior convertible notes for the years ended December 31, 2022, 2021 and 2020 included $5.3 million, $4.9 million and $3.2 million, respectively, of
    non-cash interest expense related to the amortization of debt issuance costs for our convertible notes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Financing Arrangements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Operating Facilities&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In July 2017, we purchased the building that houses our primary R&amp;amp;D facility for $79.4 million and our manufacturing facility for $14.0 million. We financed the purchase
    of these two facilities with mortgage debt of $60.4
    million in total. Our primary R&amp;amp;D facility mortgage had an interest rate of 3.88 percent. Our manufacturing facility mortgage has an
    interest rate of 4.20 percent. During the first five years of both mortgages, we were only required to make interest payments. We began making principal payments in 2022. Our manufacturing facility mortgage matures in August 2027. We repaid
    our primary R&amp;amp;D facility mortgage in October 2022 in conjunction with a sale and leaseback transaction.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we concurrently entered into two purchase and sale agreements with a real estate investor. Under the agreements, we sold and leased back the facilities at our headquarters location in Carlsbad, California and will sell,
    subject to meeting certain closing conditions, two lots of undeveloped land adjacent to our headquarters. We sold the facilities at our
    headquarters, which includes our primary R&amp;amp;D facility, for a total purchase price of $263.4 million and we expect to receive total proceeds
    of $33.0 million upon the close of the sale of the two
    lots. We used a portion of the sale proceeds to extinguish our outstanding mortgage debt on our primary R&amp;amp;D facility of $51.3 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Debt Maturity Schedules&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2022 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,281&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;550,107&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;595&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;633,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;447&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt and mortgage maturities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,194,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion included in other current liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Fixed and determinable interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,526&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,175,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Royalty Revenue Monetization&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of
    our future SPINRAZA and pelacarsen royalties we are entitled to under our agreements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone
    payments. Under the terms of the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027,
    increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In addition, Royalty Pharma will receive 25 percent of
    any future royalty payments on pelacarsen, our medicine in development for lipoprotein(a), or Lp(a), driven cardiovascular disease. Royalty Pharma&#x2019;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma
    reach either $475 million or $550
    million, depending on the timing and occurrence of FDA approval of pelacarsen. We will begin accounting for the royalty monetization agreement in the first quarter of 2023.&lt;/div&gt;
</us-gaap:DebtDisclosureTextBlock>
    <us-gaap:ScheduleOfDebtInstrumentsTextBlock
      contextRef="c20220101to20221231"
      id="Text_a4959bdb175f4cf6a490ada2282e4021">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The carrying value of our long-term obligations was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0 percent&lt;/span&gt;
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;622,242&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;619,119&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;0.125 percent&lt;/span&gt;
            convertible senior notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;544,504&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;542,314&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;186,156&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;22,058&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Mortgage debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,998&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;60,054&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,295&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,505&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,369,195&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,251,050&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: current portion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,535&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,526&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total Long-Term Obligations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,361,660&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,247,524&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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      decimals="-3"
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      unitRef="U001">619119000</us-gaap:ConvertibleDebt>
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      decimals="5"
      id="Fact_c90fc1b75dae48149c6db234063ef8c3"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_a0c41d10f5ab4db7b875a1c15ae5b5fa"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:ConvertibleDebt
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-3"
      id="Fact_d2942608f57748bdabb18c2dc442d75b"
      unitRef="U001">544504000</us-gaap:ConvertibleDebt>
    <us-gaap:ConvertibleDebt
      contextRef="c20211231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-3"
      id="Fact_81ca00edf85442d7a959529afc711233"
      unitRef="U001">542314000</us-gaap:ConvertibleDebt>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20221231"
      decimals="-3"
      id="Fact_3fc509e3ce564c3bbe4ada075c9f6bf3"
      unitRef="U001">186156000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20211231"
      decimals="-3"
      id="Fact_8f7e7fa2aaf644beafdec103f6046e51"
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    <us-gaap:LoansPayableToBank
      contextRef="c20221231"
      decimals="-3"
      id="Fact_7526ddee5b884532b24be01e4d495612"
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    <us-gaap:LoansPayableToBank
      contextRef="c20211231"
      decimals="-3"
      id="Fact_1a31cb06bce14608b6b4bc53c537a2e8"
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      contextRef="c20221231"
      decimals="-3"
      id="Fact_4f4ce1cf534445a182bc4dc79c4da3ed"
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    <us-gaap:OtherLiabilities
      contextRef="c20211231"
      decimals="-3"
      id="Fact_14ee837947184542bf24c811e63d710b"
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      decimals="-3"
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      contextRef="c20221231"
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      id="Fact_147209ef0e4d4ccf9a6541966995a76b"
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      contextRef="c20211231"
      decimals="-3"
      id="Fact_85488b1118b143d68b8dce7fa49d282e"
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    <us-gaap:RepaymentsOfConvertibleDebt
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      decimals="-5"
      id="Fact_0338cdf05d8b4010aab079cd2900de8e"
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    <us-gaap:ConvertibleDebtTableTextBlock
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022,
    we had the following 0% Notes outstanding (in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;632.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_ca0956ae2da341f1b584cfebcf6fbda4"&gt;April 2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;76.39&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022,
    we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: top; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;0.125% Notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Outstanding principal balance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;548.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Unamortized debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Maturity date&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="-sec-ix-hidden:Fact_823fe367bb0d42249b87ea8d290aa62a"&gt;December 2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.125 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: top; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5 percent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Conversion price per share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;83.28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective conversion price per share with call spread&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;123.38&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total shares of common stock subject to conversion&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ConvertibleDebtTableTextBlock>
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      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
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      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
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      unitRef="U001">548800000</us-gaap:DebtInstrumentCarryingAmount>
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      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_55f5a350ea2d4246b94e3459c056190d"
      unitRef="U001">4300000</us-gaap:DeferredFinanceCostsNet>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_77ce30228a504648ab1de2372b883044"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateEffectivePercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="3"
      id="Fact_38b86a39fb2842d6a81312dccbaddbe1"
      unitRef="U003">0.005</us-gaap:DebtInstrumentInterestRateEffectivePercentage>
    <us-gaap:DebtInstrumentConvertibleConversionPrice1
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_c206e30ca6b74e60bf7326d84b35cafd"
      unitRef="U004">83.28</us-gaap:DebtInstrumentConvertibleConversionPrice1>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_6cfe644c01ee43fe97a41569dbecd6ca"
      unitRef="U004">123.38</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <ions:DebtInstrumentConvertibleSharesSubjectToConversion
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_48c4e1d5cd6d4bcb84472d42df72435a"
      unitRef="U002">6600000</ions:DebtInstrumentConvertibleSharesSubjectToConversion>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_add9814b12a1420392f4e754754c3f5e"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_7c6c6a40bf924b02a94e810787ecc6df"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_d5f2df0b736f4a5cb82043f0a32c8911"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_c030555eba6d4c8b89018fa35171b715"
      unitRef="U004">123.38</ions:DebtInstrumentConvertibleConversionPriceIncludingCallSpread>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_a06fad74f62f4cce85190746d0159678"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:CallSpread
      contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_eb1b2b5964d74e02b285e1f179e406cb"
      unitRef="U001">52600000</ions:CallSpread>
    <us-gaap:PaymentsForHedgeFinancingActivities
      contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_a8ef89890b1849959a4e79cddecf2b34"
      unitRef="U001">108700000</us-gaap:PaymentsForHedgeFinancingActivities>
    <us-gaap:ProceedsFromIssuanceOfWarrants
      contextRef="c20191201to20191231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="-5"
      id="Fact_fda60b63b1b64c389d557236420032be"
      unitRef="U001">56100000</us-gaap:ProceedsFromIssuanceOfWarrants>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_124d77bb56934d7a9970251719ea367d"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_2d5b3c670d1144aab03131c0abc16610"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_8fd1f36899ac455daca2bb87de1df977"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_11c62c6c5c4a4a88acf4a54c3891b368"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_7438638d57584dfb92975e16d0bb70f8"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_11df1b58ae8844809f1ce3cb7b4b0633"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentRepurchasedFaceAmount
      contextRef="c20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_173429ae27c140dcbd0901c416b69acd"
      unitRef="U001">247900000</us-gaap:DebtInstrumentRepurchasedFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_d712328617e84590b7cad8ab33d7d20d"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:GainsLossesOnExtinguishmentOfDebt
      contextRef="c20210401to20210430_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_487566fe6bf14047a56b88d31ba8ac5a"
      unitRef="U001">8600000</us-gaap:GainsLossesOnExtinguishmentOfDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_b7dffcd402124b23933942c2219bdcd6"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_929e5d1b838f4adc965db63b3eb9c93e"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_8a3fa1e156a4466f8ecc35ee505d2c3b"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:RepaymentsOfConvertibleDebt
      contextRef="c20211101to20211130_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="-5"
      id="Fact_9e0d098270c84c5797fa91e125b8551f"
      unitRef="U001">62000000</us-gaap:RepaymentsOfConvertibleDebt>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_ca8ad11ea8114d63bada097b91311cd0"
      unitRef="U003">0</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="5"
      id="Fact_f182b1871b684cf1818024f6e203ac62"
      unitRef="U003">0.00125</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange
      contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0125PercentMember"
      decimals="2"
      id="Fact_d779e40c25674ddf9fd1ba75ff4b61ab"
      unitRef="U003">1</ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange>
    <ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange
      contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotes0PercentMember"
      decimals="2"
      id="Fact_5263592fee374a07839e2d8696db42e3"
      unitRef="U003">1</ions:DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20221231_DebtInstrumentAxis_ConvertibleSeniorNotes1PercentMember"
      decimals="2"
      id="Fact_fc0710aa0f424da783b2a744c9736458"
      unitRef="U003">0.01</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20220101to20221231_DebtInstrumentAxis_ConvertibleSeniorNotesMember"
      decimals="-5"
      id="Fact_7929643c46eb4d899bb5eb0f39b314e4"
      unitRef="U001">5300000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20210101to20211231_DebtInstrumentAxis_ConvertibleSeniorNotesMember"
      decimals="-5"
      id="Fact_9665623f5c3b4275a1389e2903feec32"
      unitRef="U001">4900000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:AmortizationOfFinancingCosts
      contextRef="c20200101to20201231_DebtInstrumentAxis_ConvertibleSeniorNotesMember"
      decimals="-5"
      id="Fact_88c7dc0fce0543bba9a37f924f25ee3b"
      unitRef="U001">3200000</us-gaap:AmortizationOfFinancingCosts>
    <us-gaap:PaymentsToAcquireBuildings
      contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember"
      decimals="-5"
      id="Fact_4a0c024b965c4f51b897f9cf5bc80424"
      unitRef="U001">79400000</us-gaap:PaymentsToAcquireBuildings>
    <us-gaap:PaymentsToAcquireBuildings
      contextRef="c20170701to20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember"
      decimals="-5"
      id="Fact_06974c574f644e5baacbd3f8e2c599a6"
      unitRef="U001">14000000</us-gaap:PaymentsToAcquireBuildings>
    <ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt
      contextRef="c20170701to20170731"
      decimals="INF"
      id="Fact_802514d6121f4f3ca8efa9133eb869cd"
      unitRef="U013">2</ions:NumberOfPurchasedFacilitiesFinancedWithMortgageDebt>
    <us-gaap:DebtInstrumentFaceAmount
      contextRef="c20170731_DebtInstrumentAxis_LongTermMortgageDebtMember"
      decimals="-5"
      id="Fact_1c1b0d341f0d4a39b8dd7164eab2e39d"
      unitRef="U001">60400000</us-gaap:DebtInstrumentFaceAmount>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_PrimaryResearchAndDevelopmentFacilityMember"
      decimals="4"
      id="Fact_2e21e0a6347e447a8991607c0227050a"
      unitRef="U003">0.0388</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <us-gaap:DebtInstrumentInterestRateStatedPercentage
      contextRef="c20170731_PropertyPlantAndEquipmentByTypeAxis_ManufacturingFacilityMember"
      decimals="4"
      id="Fact_b8df62c274f14f0499a84c79aa3dd4f9"
      unitRef="U003">0.042</us-gaap:DebtInstrumentInterestRateStatedPercentage>
    <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan
      contextRef="c20220101to20221231_DebtInstrumentAxis_ManufacturingFacilityMortgageMember"
      id="Fact_cec9dfdd051e4462bf766547d85be9b4">P5Y</ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan>
    <ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan
      contextRef="c20220101to20221231_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember"
      id="Fact_885a5330a5d64c1ca25849873c2df457">P5Y</ions:PeriodToMakeInterestOnlyPaymentsOnMortgageLoan>
    <ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor
      contextRef="c20221001to20221031"
      decimals="INF"
      id="Fact_8733f15524b344938a5622966d91cd3f"
      unitRef="U014">2</ions:NumberOfPurchaseAndSaleAgreementsEnteredIntoWithRealEstateInvestor>
    <ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="INF"
      id="Fact_d19a188162204459bb6a7d2c5b905500"
      unitRef="U015">2</ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement>
    <us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment
      contextRef="c20221001to20221031_PropertyPlantAndEquipmentByTypeAxis_HeadquartersLocationInCarlsbadCaliforniaMember"
      decimals="-5"
      id="Fact_995ff98913014ef6a5f5fc51445c7128"
      unitRef="U001">263400000</us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment>
    <us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment
      contextRef="c20230101to20230222_PropertyPlantAndEquipmentByTypeAxis_LandMember_StatementScenarioAxis_ScenarioForecastMember"
      decimals="-5"
      id="Fact_451514a20aac4c9e987035912240b2d5"
      unitRef="U001">33000000</us-gaap:ProceedsFromSaleOfPropertyPlantAndEquipment>
    <ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement
      contextRef="c20221031_PropertyPlantAndEquipmentByTypeAxis_LandMember"
      decimals="INF"
      id="Fact_a8c5588ea2e04cc99ff52c8cb117bb7b"
      unitRef="U015">2</ions:NumberOfLotsOfUndevelopedLandIncludedInPurchaseAndSaleAgreement>
    <us-gaap:RepaymentsOfSecuredDebt
      contextRef="c20221001to20221031_DebtInstrumentAxis_PrimaryResearchAndDevelopmentFacilityMortgageMember"
      decimals="-5"
      id="Fact_ee22c79230e54d5289dec6e7979e0722"
      unitRef="U001">51300000</us-gaap:RepaymentsOfSecuredDebt>
    <srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Annual convertible and mortgage debt maturities, including fixed and determinable interest, at December 31, 2022 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2023&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,281&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;550,107&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;595&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2026&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;633,095&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2027&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;447&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;8,708&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total debt and mortgage maturities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,194,233&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion included in other current liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(151&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Fixed and determinable interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,526&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Debt issuance costs&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14,831&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,175,725&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</srt:ContractualObligationFiscalYearMaturityScheduleTableTextBlock>
    <us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths
      contextRef="c20221231"
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      contextRef="c20221231"
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      id="Fact_6b7eb3455bef4825bec5934f0ca8a9f2"
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      id="Fact_5163088d8dfb4bd8afb6a945c3e15b83"
      unitRef="U001">633095000</us-gaap:LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour>
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      contextRef="c20221231"
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    <us-gaap:LongTermDebt
      contextRef="c20221231"
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      id="Fact_41f58f8c96774a38af7b7c1cc41eabb9"
      unitRef="U001">1194233000</us-gaap:LongTermDebt>
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      id="Fact_bc879ac3c37f49de90a976632193e86e"
      unitRef="U001">151000</us-gaap:LongTermDebtCurrent>
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      id="Fact_ef9db53e88e14db9b13d2afa08b9cc23"
      unitRef="U001">3526000</us-gaap:InterestPayableCurrentAndNoncurrent>
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    <us-gaap:LesseeOperatingLeasesTextBlock
      contextRef="c20220101to20221231"
      id="Text_816a383efe384026825a397c06709b4a">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Operating Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Carlsbad Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We lease a facility adjacent to our manufacturing facility that has laboratory and office space that we use to support our manufacturing
    facility. We lease this space under a non-cancelable operating lease. In May 2020, we exercised our option to extend our lease, extending our lease term from June 2021 to August 2026. We have one remaining option to extend the lease for an additional five-year period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also lease additional office spaces in Carlsbad. We lease these spaces under non-cancelable operating leases. In September 2022, we
    exercised our option to extend one of these leases, extending our term from January 2023 to May 2027. We have no remaining options to extend this lease. Our other office space lease in Carlsbad has an initial term ending in 2023.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed above in the section titled, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Financing Arrangements&lt;/span&gt;, we lease our headquarters, which includes our primary R&amp;amp;D facility, as part of a sale and leaseback transaction that closed in October 2022. The initial lease term for our headquarters facilities is 15 years with options to extend the lease for 2
    additional terms of five years each. We determined at lease inception that it was not reasonably certain that we would exercise any of the
    options to extend the lease. We expect our lease payments over the initial term to total approximately $280 million. In connection with the sale
    of our two undeveloped lots, we will enter into a build-to-suit lease agreement with the same real estate investor who will build a new R&amp;amp;D
    facility for us on those lots. Once this new facility is completed, our lease will commence.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Oceanside Lease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2022, we entered into a build-to-suit lease agreement to lease a development chemistry and manufacturing facility in Oceanside,
    California. The lessor will develop and construct a building composed of manufacturing space, office space, research and development space and warehouse space. We will design and construct tenant improvements to customize the facility&#x2019;s interior space.
    We will lease the facility for an initial term of 20 years and 3 months with options to extend the lease for two additional terms of 10 years each. The lease
    will commence when the lessor&#x2019;s construction is complete and we are able to begin constructing tenant improvements.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Boston Leases&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We entered into an operating lease agreement for office space located in Boston, Massachusetts which commenced in August 2018. We are
    leasing this space under a non-cancelable operating lease with an initial term ending after 123 months and an option to extend the lease for an
    additional five-year term. Under the lease agreement, we received a three-month free rent period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2022, we entered into a sublease agreement for our office space located in Boston, Massachusetts. The sublease commencement
    date was in January 2022 when the office space was ready for our tenant&#x2019;s occupancy. We are subleasing this space under a non-cancelable operating sublease with a sublease term ending 83 months following the sublease commencement date with no option to extend the sublease. Under the sublease agreement we provided a seven-month free rent period, which commenced on January 6, 2022. We will receive lease payments over the sublease term totaling $9.6 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We entered into an operating lease agreement for another office space located in Boston, Massachusetts which commenced in November 2021.
    We are leasing this space under a non-cancelable operating lease with an initial term ending 91 months following the lease commencement date and
    an option to extend the lease for &lt;span style="-sec-ix-hidden:Fact_ddceec580074417fbe536c7c2d5d252c"&gt;an&lt;/span&gt; additional five-year
    term. Under the lease agreement, we received a seven-month free rent period, which commenced on November 1, 2021. Our lease payments over the
    initial term total $6.8 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we determined our lease term for our operating lease right-of-use assets and lease liabilities for these leases, we did not include
    the extension options for these leases in the original lease term because it was not reasonably certain we would exercise those extension options.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;186.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.8 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022,
    2021, and 2020 we paid $4.0 million, $3.3 million and $3.8 million of lease payments, which were included in operating activities in our consolidated statements of cash flows.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022, the future payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Year ending December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,640&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2026&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,800&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;196,911&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;299,594&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Imputed interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(113,438&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (included in &lt;span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32"&gt;other current liabilities&lt;/span&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,215&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,941&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Rent expense was $8.3 million,
    $3.4 million and $3.7 million for the
    years ended December 31, 2022, 2021
    and 2020, respectively. &lt;/div&gt;
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    <us-gaap:LesseeOperatingLeaseTermOfContract
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_f252e6bc1ca849dfb22869bd4a71369a">P91M</us-gaap:LesseeOperatingLeaseTermOfContract>
    <us-gaap:LesseeOperatingLeaseRenewalTerm
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_093b7e88a1474547a8fe7129936aa7cd">P5Y</us-gaap:LesseeOperatingLeaseRenewalTerm>
    <ions:LesseeOperatingLeasePeriodOfFreeRent
      contextRef="c20220101to20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      id="Fact_99931a7181e04c71bbd9180a5f64f952">P7M</ions:LesseeOperatingLeasePeriodOfFreeRent>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue
      contextRef="c20221231_PropertyPlantAndEquipmentByTypeAxis_AnotherOfficeSpaceInBostonMember"
      decimals="-5"
      id="Fact_c350c485d2194852998ea1b496903ff5"
      unitRef="U001">6800000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDue>
    <ions:LesseeOperatingLeaseInformationTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_e4fd6084d7e2468e95eebcfebd153735">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Amounts related to our operating leases were as follows (dollar amounts in millions):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;At December 31, 2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use operating lease assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;181.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;186.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average remaining lease term&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13.8 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Weighted average discount rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</ions:LesseeOperatingLeaseInformationTableTextBlock>
    <us-gaap:OperatingLeaseRightOfUseAsset
      contextRef="c20221231"
      decimals="-5"
      id="Fact_42b72db309654cf1bdbfe546a3a2176d"
      unitRef="U001">181500000</us-gaap:OperatingLeaseRightOfUseAsset>
    <us-gaap:OperatingLeaseLiability
      contextRef="c20221231"
      decimals="-5"
      id="Fact_44caa1523d334df48c7b2561738097e4"
      unitRef="U001">186200000</us-gaap:OperatingLeaseLiability>
    <us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1
      contextRef="c20221231"
      id="Fact_ccfd1bbd8568445fb43b6a1d85973cc7">P13Y9M18D</us-gaap:OperatingLeaseWeightedAverageRemainingLeaseTerm1>
    <us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent
      contextRef="c20221231"
      decimals="3"
      id="Fact_0f6726aa9c174130a3010b4dad4799ef"
      unitRef="U003">0.069</us-gaap:OperatingLeaseWeightedAverageDiscountRatePercent>
    <us-gaap:OperatingLeasePayments
      contextRef="c20220101to20221231"
      decimals="-5"
      id="Fact_826cead5743b4e90a9d8b807e97fe422"
      unitRef="U001">4000000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20210101to20211231"
      decimals="-5"
      id="Fact_297fcce7f2e44b348fe63e7be360cf7c"
      unitRef="U001">3300000</us-gaap:OperatingLeasePayments>
    <us-gaap:OperatingLeasePayments
      contextRef="c20200101to20201231"
      decimals="-5"
      id="Fact_50e928616e964a8c94f28d1e4409995c"
      unitRef="U001">3800000</us-gaap:OperatingLeasePayments>
    <us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_4ac550fe12b346a487d1639e48d94f8d">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As of December 31, 2022, the future payments for our operating lease liabilities are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Operating&lt;/span&gt; &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;Leases&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Year ending December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,071&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2024&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -0.2pt; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;2025&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,640&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2026&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,781&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;20,800&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Thereafter&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;196,911&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total minimum lease payments&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;299,594&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Imputed interest&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(113,438&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 18.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Less: Current portion (included in &lt;span style="-sec-ix-hidden:Fact_9874929ec96442469df0f0fc39baed32"&gt;other current liabilities&lt;/span&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(7,215&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 88%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 36.7pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;178,941&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:LesseeOperatingLeaseLiabilityMaturityTableTextBlock>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths
      contextRef="c20221231"
      decimals="-3"
      id="Fact_9240bc8118ea402f85a2119c7486d19d"
      unitRef="U001">20071000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueNextTwelveMonths>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo
      contextRef="c20221231"
      decimals="-3"
      id="Fact_4609f99ef9604c9aae3baed51a3c3fed"
      unitRef="U001">20391000</us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearTwo>
    <us-gaap:LesseeOperatingLeaseLiabilityPaymentsDueYearThree
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt;5. Stockholders&lt;/span&gt;&#x2019;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-weight: bold;"&gt; Equity&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Preferred Stock&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are authorized to issue up to 15
    million shares of &#x201c;blank check&#x201d; Preferred Stock. As of December 31, 2022, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2022.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Common Stock&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022 and 2021, we had 300 million shares of common
    stock authorized, of which 142.1 million and 141.2 million were issued and outstanding, respectively. As of December 31, 2022,
    total common shares reserved for future issuance were 43.2 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022,
    2021 and 2020, we issued 1.2 million, 1.1 million and 1.7 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net
    proceeds from these transactions of $6.4 million, $11.6
    million and $52.0 million in 2022,
    2021 and 2020, respectively.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Share Repurchase Program&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2019, our board of directors approved a share repurchase program of up to $125 million of our common stock. In 2019, we repurchased 535,000 shares for $34.4 million. In the first quarter of 2020, we repurchased an additional 1.5 million shares for $90.5 million.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock Plans&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;1989 Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 1989, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that, as amended, provides
    for the issuance of non-qualified and incentive stock options for the purchase of up to 20.0 million shares of common stock to our employees,
    directors, and consultants. The plan expires in January 2024. The 1989 Plan does not allow us to grant stock bonuses or restricted stock awards and prohibits us from repricing any options outstanding under the plan unless our stockholders approve the
    repricing. Options vest over a four-year period, with 25percent exercisable at the end of one year from the date of the grant and the
    balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. At December 31, 2022, a total of 12 thousand options were outstanding, of which
    options to purchase 12 thousand shares were exercisable, and 65 thousand shares were available for future grant under the 1989 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2011 Equity Incentive Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In March 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the
    issuance of stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and performance cash awards to our employees, directors, and consultants. In June 2015, May 2017 and June 2019, after receiving approval from
    our stockholders, we amended our 2011 Equity Incentive Plan, or&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; 2011 Plan,&lt;/span&gt; to increase the total number of shares reserved for issuance. We increased the shares
    available under our 2011 Equity Incentive Plan from 5.5 million to 11.0 million in June 2015, from 11.0 million to 16.0 million in May 2017 and from 16.0 million to 23.0 million in June 2019. In the second quarter of 2021, after receiving approval from our stockholders, we amended our &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2011 Plan. The amendment increased the total number of shares of common stock authorized for issuance under the 2011 Plan from &lt;/span&gt;23.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;29.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and added a fungible share counting ratio whereby the share reserve will be reduced by &lt;/span&gt;1.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; shares for each share of common stock issued pursuant to a full value award (i.e., RSU or PRSU) and increased by
    &lt;/span&gt;1.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; shares for each share of common stock returning from a
      full value award. &lt;/span&gt;The plan expires in June 2031. The 2011 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock appreciation rights or cancel any outstanding stock options or stock appreciation rights
    that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our stockholders approve such action. Currently we anticipate awarding only stock options, RSU
    and PRSU awards to our employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant
    and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a
    term of ten years. We have granted restricted stock unit awards to our employees under the 2011 Plan which vest annually over a four-year period. At December 31, 2022, a
    total of 13.7 million options were outstanding, of which 9.4 million were exercisable, 2.7 million restricted stock unit awards were
    outstanding, and 5.8 million shares were available for future grant under the 2011 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the 2011 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur. In addition, we implemented a change of control and severance benefit plan that provides for change of control and severance benefits to our executive officers, including our
    chief executive officer and chief financial officer, and vice presidents. If one of our executive officers or vice presidents is terminated or
    resigns for good reason during the period that begins three months before and ends twelve months following a change in control of the company, the impacted employee&#x2019;s stock options and RSUs vesting will accelerate for options and RSUs outstanding as of the termination date.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2020 Equity Incentive Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In connection with the Akcea Merger in October 2020, we
      assumed the unallocated portion of the available share reserve under the Akcea 2015 Equity Incentive Plan. In December 2020, we amended and restated the Akcea 2015 equity plan, including renaming the plan as the Ionis Pharmaceuticals, Inc. 2020
      Equity Incentive Plan, or 2020 Plan. The 2020 Plan provided for the issuance of up to &lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million shares of our Common Stock to our employees, directors and consultants who were employees of Akcea prior to the Akcea Merger. In the second quarter of 2021, our Compensation Committee approved an amendment
      to the 2020 Plan. The amendment decreased the total number of shares of common stock authorized for issuance under the 2020 Plan from approximately &lt;/span&gt;2.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;1.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. We assumed the 2020 Plan in connection with Ionis&#x2019; reacquisition of all of the outstanding shares of Akcea Therapeutics, Inc. as part of the Akcea Merger.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The plan expires in December 2025. The 2020 Plan does not allow us to reduce the exercise price of any outstanding stock options or stock
    appreciation rights or cancel any outstanding stock options or stock appreciation rights that have an exercise price or strike price greater than the current fair market value of the common stock in exchange for cash or other stock awards unless our
    stockholders approve such action. Currently we anticipate awarding only stock options and RSU awards to our eligible employees, directors and consultants. Options vest over a four-year period, with 25 percent exercisable at the end of one year from the date of the grant and the balance vesting ratably, on a monthly basis, thereafter and have a term of seven years. Options granted after December 31, 2021 have a term of ten years.
    We have granted restricted stock unit awards to our employees under the 2020 Plan which vest annually over a four-year period. At December 31, 2022, a total of 0.3 million
    options were outstanding, of which 61 thousand were exercisable, 0.1 million restricted stock unit awards were outstanding, and 1.2 million shares were
    available for future grant under the 2020 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the 2020 Plan, we may issue a stock award with additional acceleration of vesting and exercisability upon or after a change in
    control. In the absence of such provisions, no such acceleration will occur.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Corporate Transactions and Change in Control under 2011 and 2020 Plans&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the event of certain significant corporate transactions, our Board of Directors has the discretion to take one or more of the following
    actions with respect to outstanding stock awards under the 2011 and 2020 Plans:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for assumption, continuation, or substitution of a stock award by a surviving or acquiring entity (or its parent company);&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the assignment of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award to the surviving or
            acquiring corporation (or its parent company);&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;accelerate the vesting and exercisability of a stock award followed by the termination of the stock award;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the lapse of any reacquisition or repurchase rights applicable to any shares of our common stock issued pursuant to a stock award;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;cancel or arrange for the cancellation of a stock award, to the extent not vested or not exercised prior to the effective date of the corporate transaction, in exchange
            for cash consideration, if any, as the Board, in its sole discretion, may consider appropriate; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;arrange for the surrender of a stock award in exchange for a payment equal to the excess of (a) the value of the property the holder of the stock award would have
            received upon the exercise of the stock award, over (b) any exercise price payable by such holder in connection with such exercise.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2002 Non-Employee Directors&#x2019; Stock Option Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2001, our Board of Directors adopted, and the stockholders subsequently approved, an amendment and restatement of the 1992
    Non-Employee Directors&#x2019; Stock Option Plan, which provides for the issuance of non-qualified stock options and restricted stock units to our non-employee directors. The name of the resulting plan is the 2002 Non-Employee Directors&#x2019; Stock Option Plan, or
    the 2002 Plan. In June 2015, after receiving approval from our stockholders, we amended our 2002 Plan to increase the total number of shares reserved for issuance from 1.2 million to 2.0 million. In June 2020, after receiving approval from our
    stockholders, we further amended our 2002 Plan. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;The amendments included:&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;An increase to the total number of shares reserved for issuance under the plan from &lt;/span&gt;2.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million to &lt;/span&gt;2.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million shares;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A reduction to the amount of the automatic awards under the plan;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;A revision to the vesting schedule of new awards granted; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;An extension of the term of the plan.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Options under this plan expire 10 years
    from the date of grant. At December 31, 2022, a total of 0.9 million options were outstanding, of which 0.8 million were exercisable, 0.1 million restricted stock unit awards were outstanding, and 0.6
    million shares were available for future grant under the 2002 Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: -18pt; margin-left: 54pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Employee Stock Purchase Plan&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In June 2009, our Board of Directors adopted, and the stockholders subsequently approved, the amendment and restatement of the ESPP and we
    reserved an additional 150,000 shares of common stock for issuance thereunder. In each of the subsequent years until 2019, we reserved an
    additional 150,000 shares of common stock for the ESPP resulting in a total of 3.2 million shares authorized under the plan as of December 31, 2022. The ESPP
    permits full-time employees to purchase common stock through payroll deductions (which cannot exceed 10percent of each employee&#x2019;s compensation)
    at the lower of 85percent of fair market value at the beginning of the purchase period or the end of each purchase period. Under the amended
    and restated ESPP, employees must hold the stock they purchase for a minimum of six months from the date of purchase. During 2022, employees purchased and we issued to employees 0.1
    million shares under the ESPP at a weighted average price of $28.57 per share. At December 31, 2022, there were 0.5 million shares available for purchase under the
    ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock Option Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2022 (in thousands, except per share and contractual life data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,089&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.04&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,864&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34.78&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Exercised&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(123&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29.35&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited/expired&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,860&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.96&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,970&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.01&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,243&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Exercisable at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.74&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.56&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,651&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The weighted-average estimated fair values of options granted were $18.66, $24.35 and $29.43 for the years ended December 31, 2022, 2021 and 2020, respectively. The total intrinsic value of options
    exercised during the years ended December 31, 2022, 2021 and 2020 were $1.4 million, $2.5 million and $15.5 million, respectively, which we determined as of the date of exercise. The amount of cash received from the exercise of stock options was $3.6 million, $8.5 million and $43.7 million for the years ended December 31, 2022, 2021 and 2020, respectively. For the year
    ended December 31, 2022, the weighted-average fair value of options exercised was $40.71. As of December 31, 2022, total unrecognized compensation cost related to
    non-vested stock options was $41.1 million. We expect to recognize this cost over a weighted average period of 1.1 years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Restricted Stock Unit Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the RSU activity for the year ended December 31, 2022 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,618&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58.05&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,401&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36.14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(958&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.05&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(295&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.61&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,766&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022,
    2021 and 2020, the
    weighted-average grant date fair value of RSUs granted was $36.14, $57.02 and $60.57 per RSU, respectively. As of December 31, 2022, total unrecognized compensation cost related to RSUs was $45.8 million. We expect to recognize this cost over a weighted average period of 1.2
    years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Performance Restricted Stock Unit Activity&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the PRSU activity for the year ended December 31, 2022 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75.03&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.11&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022,
    2021 and 2020, the
    weighted-average grant date fair value of PRSUs granted was $42.28, $77.17 and $93.09 per PRSU, respectively. As of December 31, 2022, total unrecognized compensation cost related to PRSUs was $2.4 million. We expect to recognize this cost over a weighted average period of 0.9
    years. We will adjust the total unrecognized compensation cost for future changes in estimated forfeitures.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Stock-based Compensation Expense and Valuation Information&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;533&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;456&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,991&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;73,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;115,584&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,700&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,678&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;230,117&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2020, as part of the Akcea Merger, Akcea&#x2019;s outstanding equity awards vested under Akcea&#x2019;s Plan. As a result, in 2020, we
    recognized all unrecognized stock-based compensation, which totaled $59.3 million, under Akcea&#x2019;s Plan.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Refer to Part IV, Item 15, Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization
      and Significant Accounting Policies&lt;/span&gt;, for further details on how we determine the fair value of stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;For the years ended December 31, 2022,
    2021 and 2020, we used the
    following weighted-average assumptions in our Black-Scholes calculations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.7 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Risk-Free Interest Rate.&lt;/span&gt; We base
    the risk-free interest rate assumption on observed interest rates appropriate for the term of our stock option plans or ESPP.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Dividend Yield.&lt;/span&gt; We base the
    dividend yield assumption on our history and expectation of dividend payouts. We have not paid dividends in the past and do not expect to in the future.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Volatility.&lt;/span&gt; We use an average of
    the historical stock price volatility of our stock for the Black-Scholes model. We computed the historical stock volatility based on the expected term of the awards.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Expected Life. &lt;/span&gt;The expected term
    of stock options we have granted represents the period of time that we expect them to be outstanding. Historically, we estimated the expected term of options we have granted based on actual and projected exercise patterns. In 2021, our Compensation
    Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or 2020 Plan, that increased the contractual term of stock options granted under these plans from &lt;span style="-sec-ix-hidden:Fact_bd3d24dad695460d8e7018466f08295c"&gt;&lt;span style="-sec-ix-hidden:Fact_a0ee4419d26449d89aee22da843bd7ad"&gt;seven&lt;/span&gt;&lt;/span&gt; to ten years for stock options granted on January 1, 2022
    and thereafter. We determined that we are unable to rely on our historical exercise data as a basis for estimating the expected life of stock options granted to employees following this change because the contractual term changed and we have no other
    means to reasonably estimate future exercise behavior. We therefore used the simplified method for determining the expected life of stock options granted to employees in the year ended December 31, 2022. Under the simplified method, we calculate the
    expected term as the average of the time-to-vesting and the contractual life of the options. As we gain additional historical information, we will transition to calculating our expected term based on our historical exercise patterns.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Forfeitures.&lt;/span&gt; We reduce stock-based
    compensation expense for estimated forfeitures. We estimate forfeitures at the time of grant and revise, if necessary, in subsequent periods if actual forfeitures differ from those estimates. We estimate forfeitures based on historical experience. &lt;/div&gt;
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      unitRef="U002">300000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber>
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      unitRef="U002">100000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber>
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      id="Fact_0e9dea3a9bb44f258d4a6a1eeffbb1b0"
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      decimals="-5"
      id="Fact_e55c20e37dc6464eb74bde99a3d220dc"
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      contextRef="c20150630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member"
      decimals="-5"
      id="Fact_fda3670487384cb49c8eb41d6d8f4665"
      unitRef="U002">2000000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized>
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      contextRef="c20200630_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member"
      decimals="-5"
      id="Fact_8b16c9fcbd8a4de6a3ff40e97438a3a8"
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      id="Fact_e6b00753880241348e596a82fa22bab2">P10Y</us-gaap:SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod>
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      contextRef="c20221231_PlanNameAxis_NonemployeeDirectorsStockOptionPlan2002Member"
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      id="Fact_28beff5bd3d14e0c9936c3a0e4bfd184"
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      id="Fact_5c3c554e640546a481c2968b37014870"
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      decimals="-5"
      id="Fact_d025b834777346cfa313dfb503dafd03"
      unitRef="U002">100000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsOutstandingNumber>
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      id="Fact_3b40f4cda8e040fdba6be624573711c9"
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      id="Fact_627f300828104f14b873bf05eda50f67"
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      decimals="-5"
      id="Fact_e19efe7ddb5143df982e961a832ee9c5"
      unitRef="U002">3200000</us-gaap:ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized>
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      id="Fact_36267c2abcb644b69eb45aceda22f69b"
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      decimals="2"
      id="Fact_2c284719dc094a59851d962ad33aacae"
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      decimals="-5"
      id="Fact_9bcf03b844ab41c1a8fbd64333e01f0e"
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the stock option activity under our stock plans for the year ended December 31, 2022 (in thousands, except per share and contractual life data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average Exercise&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Price Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Remaining&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Contractual Term&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Years)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Aggregate&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Intrinsic&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,089&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.04&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,864&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34.78&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Exercised&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(123&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;29.35&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited/expired&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,860&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.96&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Outstanding at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,970&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.01&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,243&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 52%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Exercisable at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,285&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53.74&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.56&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,651&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the RSU activity for the year ended December 31, 2022 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,618&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58.05&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,401&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;36.14&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(958&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.05&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(295&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.61&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,766&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;48.30&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes the PRSU activity for the year ended December 31, 2022 (in thousands, except per share data):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Number&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;of Shares&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Weighted Average&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Grant Date Fair&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Value Per Share&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2021&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Granted&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.28&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Vested&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;75.03&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 18pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cancelled/forfeited&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.11&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="text-indent: 0pt;"&gt;Non-vested at December 31, 2022&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;52.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Cost of sales&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;533&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;456&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,991&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Research, development and patent&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;73,704&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;115,584&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Selling, general and administrative&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;26,027&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;32,700&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;112,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;100,264&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;120,678&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;230,117&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Employee Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;58.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.3 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.9 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4.7 years&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis Board of Director Stock Options:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.5&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
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  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
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  &lt;tr&gt;

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          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57.6&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.4 years&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7.3 years&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6.7 years&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Ionis ESPP:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

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  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

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          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Risk-free interest rate&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.8&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Dividend yield&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Volatility&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;50.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;42.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Expected life&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: right; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6 months&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;6. Income Taxes&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;United States&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(258,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,966&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(137,222&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;818&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134,552&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our income tax expense (benefit) was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Current:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(200&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(690&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,782&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;339&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;518&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total current income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,463&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;341,728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred income tax benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;341,728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;345,191&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The
    sources and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax income (loss)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134,552&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Statutory rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(54,177&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,121&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,256&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State income tax net of federal benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,278&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37,705&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net change in valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;460,898&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(342.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss on debt transactions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,198&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,774&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred tax true-up&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(206&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax rate change&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-deductible compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,931&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other non-deductible items&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;193&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,720&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,435&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Impacts from Akcea Merger&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;364&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;345,191&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(256.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
    financial reporting purposes and the amounts used for income tax purposes.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Significant components of our deferred tax assets and liabilities as of December 31, 2022 and 2021 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Assets:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net operating loss carryovers&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,802&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,600&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;277,436&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;269,538&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,700&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,983&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Intangible and capital assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,649&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;92,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Convertible debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,384&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,681&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense limitation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,996&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized research and development expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;119,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,119&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,813&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,929&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred tax assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;858,014&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;706,346&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Liabilities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Fixed assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,303&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,504&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,159&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(313&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net deferred tax asset&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;808,722&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;697,773&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(808,722&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(697,773&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total net deferred tax assets and liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluate our deferred tax assets regularly to determine whether adjustments to the valuation allowance are appropriate due to changes in facts or
    circumstances, such as changes in expected future pre-tax earnings, tax law, interactions with taxing authorities and developments in case law. In making this evaluation, we rely on our recent history of pre-tax earnings. Our material assumptions are
    our forecasts of future pre-tax earnings and the nature and timing of future deductions and income represented by the deferred tax assets and liabilities, all of which involve the exercise of significant judgment. Although we believe our estimates are
    reasonable, we are required to use significant judgment in determining the appropriate amount of valuation allowance recorded against our deferred tax assets.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our valuation allowance increased by $111
    million from December 31, 2021 to December 31, 2022.
    The increase was primarily related to increases in our deferred tax asset for capitalized research and development expenses.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At December 31, 2022, we had
    federal and state, primarily California, tax net operating loss carryforwards of $242.8 million and $461.3 million, respectively. Our federal tax loss carryforwards are available indefinitely. Our California tax loss carryforwards will begin to expire in 2031. At December 31, 2022, we also had federal and California research and development tax credit carryforwards of $224.9 million and $110.7 million, respectively. Our federal research and development
    tax credit carryforwards will begin to expire in 2035. Our California research and development tax credit carryforwards are available indefinitely.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Utilization of the net operating loss and tax credit carryforwards may be subject to an annual limitation due to the ownership change
    limitations provided by the Internal Revenue Code of 1986, as amended, and similar state provisions. The annual limitation may result in the expiration of net operating losses and credits before utilization.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We analyze filing positions in all U.S. federal, state and foreign jurisdictions where we file income tax returns, and all open tax years
    in these jurisdictions to determine if we have any uncertain tax positions on any of our income tax returns. We recognize the impact of an uncertain tax position on an income tax return at the largest amount that the relevant taxing authority is
    more-likely-than not to sustain upon audit. We do not recognize uncertain income tax positions if they have less than 50 percent likelihood of the applicable tax authority sustaining our position.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes our gross unrecognized tax benefits &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in
      thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(267&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(695&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,154&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for current period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,354&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,510&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Included in the balance of unrecognized tax benefits at December 31, 2022, 2021 and 2020 was $6.2 million, $6.2 million and $6.4 million respectively, that if we recognized, could impact our
    effective tax rate, subject to our remaining valuation allowance.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We estimate that it is reasonably possible that the balance of our gross unrecognized tax benefits may decrease by approximately $15.0 million within the next 12 months due to the lapse of statute of limitations on underlying tax positions primarily related to tax credits.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We recognize interest and/or penalties related to income tax matters in income tax expense. During the years ended December 31, 2022, 2021 and 2020, we recognized $0.8 million, $0.5 million and $0.3 million, respectively, of
    accrued interest and penalties related to gross unrecognized tax benefits.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We are subject to taxation in the U.S. and various state and foreign jurisdictions. The tax years 2018 through 2021 remain open to
    examination by major taxing jurisdictions, primarily federal and California, although net operating loss and credit carryforwards generated prior to 2018 may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if
    they have been used in an open period or are used in a future period.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We do not provide for a U.S. income tax liability and foreign
      withholding taxes on undistributed foreign earnings of our foreign subsidiaries as we consider those earnings to be permanently reinvested. It is not practicable for us to calculate the amount of unrecognized deferred tax liabilities associated with
      these earnings&lt;/span&gt;.&lt;/div&gt;
</us-gaap:IncomeTaxDisclosureTextBlock>
    <us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_7281bd0eb54443b994694c659a6a8f66">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes is comprised of (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;United States&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(258,493&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,966&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(137,222&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;508&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;818&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,670&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) before income taxes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134,552&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:ScheduleOfIncomeBeforeIncomeTaxDomesticAndForeignTableTextBlock>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_1154d9477ea5403c89bcaba61b591e79"
      unitRef="U001">-258493000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_74d3abad4f744e0aa68801acc3a6ed6b"
      unitRef="U001">-29966000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic
      contextRef="c20200101to20201231"
      decimals="-3"
      id="Fact_8977ca2c8272434794efd8259c5f22b7"
      unitRef="U001">-137222000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesDomestic>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_70ca994a31be49619caefe5e71de1587"
      unitRef="U001">508000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_8425f2adaf6948cdb4db61cdf7def1fc"
      unitRef="U001">818000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign
      contextRef="c20200101to20201231"
      decimals="-3"
      id="Fact_15eeca6092a14a5c9b839eb716ea8ae4"
      unitRef="U001">2670000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesForeign>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20220101to20221231"
      decimals="-3"
      id="Fact_317564d38d3f4684aaa47f65a5d386e8"
      unitRef="U001">-257985000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_9fd05fd89e164623ad7d51c758cf30c6"
      unitRef="U001">-29148000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest
      contextRef="c20200101to20201231"
      decimals="-3"
      id="Fact_225bd758b4d047a9b56b2a1266e8768e"
      unitRef="U001">-134552000</us-gaap:IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest>
    <us-gaap:ScheduleOfComponentsOfIncomeTaxExpenseBenefitTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_d123dff19b9e4823b03cc17efdea0755">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our income tax expense (benefit) was as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Current:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,522&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(200&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(837&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,129&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(690&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,782&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;339&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;518&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total current income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,463&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Federal&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;341,728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred income tax benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;341,728&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total income tax expense (benefit)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;345,191&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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      contextRef="c20210101to20211231"
      decimals="-3"
      id="Fact_18598915ff304ad69c4f603530fa17ba"
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      contextRef="c20200101to20201231"
      decimals="-3"
      id="Fact_b16b487bd08b4f16b0833b9f760c9124"
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to income (loss) before taxes. The
    sources and tax effects of the differences are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="22" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Pre-tax income (loss)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(257,985&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(29,148&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(134,552&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Statutory rate&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(54,177&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6,121&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(28,256&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;State income tax net of federal benefit&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13,622&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,278&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(14.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(37,705&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;28.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Foreign&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;143&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;49&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net change in valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(40.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2,885&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(9.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;460,898&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(342.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Loss on debt transactions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;262&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(39,729&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(23,198&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(18,774&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred tax true-up&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(20&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(206&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax rate change&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,091&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12,838&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(32,951&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;24.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Non-deductible compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(17.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,931&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other non-deductible items&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;57&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;84&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;193&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;14,030&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4,720&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(16.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17,435&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(13.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Impacts from Akcea Merger&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(22,032&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;16.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;364&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,503&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,391&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 28%; padding-bottom: 4px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effective rate&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11,737&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(551&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.9&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;345,191&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(256.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Significant components of our deferred tax assets and liabilities as of December 31, 2022 and 2021 are as follows (in thousands):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="6" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Assets:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net operating loss carryovers&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;87,802&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,600&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Tax credits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;277,436&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;269,538&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;85,700&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,330&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Stock-based compensation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,983&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;86,611&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Intangible and capital assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;104,649&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;92,542&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Convertible debt&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34,384&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,681&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Interest expense limitation&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,996&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Capitalized research and development expenses&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;119,635&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Long-term lease liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;45,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5,119&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;15,813&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;9,929&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total deferred tax assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;858,014&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;706,346&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Deferred Tax Liabilities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Fixed assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,475&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3,303&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Right-of-use assets&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(44,504&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4,159&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Other&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(313&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1,111&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net deferred tax asset&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;808,722&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;697,773&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Valuation allowance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(808,722&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(697,773&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total net deferred tax assets and liabilities&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following table summarizes our gross unrecognized tax benefits &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;(in
      thousands):&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Beginning balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;69,784&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Decrease for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(267&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(695&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(24,154&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for prior period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;259&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;263&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7,023&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Increase for current period tax positions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,490&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,354&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,510&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Ending balance of unrecognized tax benefits&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56,567&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;55,085&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;54,163&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;7. Collaborative Arrangements and Licensing Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Strategic Partnership&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Biogen&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological
    disorders. These collaborations combine our expertise in creating antisense medicines with Biogen&#x2019;s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with
    spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, AS, AD&lt;sub&gt;&#160;&lt;/sub&gt;and
    Parkinson&#x2019;s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through December 31, 2022, we have received more than $3.4 billion from our
    Biogen collaborations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Spinal Muscular Atrophy Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;SPINRAZA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2012, we entered into a collaboration agreement
      with Biogen to develop and commercialize SPINRAZA.&lt;/span&gt;&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we earned more than $&lt;/span&gt;1.8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in total revenue under our SPINRAZA collaboration, including more than $&lt;/span&gt;1.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; billion in revenue from SPINRAZA royalties and more than $&lt;/span&gt;425&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in R&amp;amp;D revenue. We are receiving tiered royalties ranging from
    &lt;/span&gt;11 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; to &lt;/span&gt;15 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales of SPINRAZA. We have exclusively in-licensed patents related to SPINRAZA from
      Cold Spring Harbor Laboratory and the University of Massachusetts. We pay Cold Spring Harbor Laboratory and the University of Massachusetts a low single digit royalty on net sales of SPINRAZA. Biogen is responsible for all global development,
      regulatory and commercialization activities and costs for SPINRAZA. We completed our performance obligations under our collaboration in 2016&lt;/span&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, we entered into a royalty purchase agreement with Royalty Pharma in which Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. Royalty
    Pharma&#x2019;s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen, which Novartis is developing. Refer to Part IV, Item 15, Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for further discussion of this agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;New antisense medicines for the treatment of SMA&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In December 2017, we entered into a collaboration agreement
      with Biogen to &lt;/span&gt;identify &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;new antisense medicines for the treatment of SMA&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Biogen has the option to license therapies arising out of this collaboration following the completion of
      preclinical studies. Upon licensing, Biogen &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;will be responsible for global development, regulatory and commercialization activities and costs for such therapies&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. Under the collaboration agreement, we received a &lt;/span&gt;$25
    million&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; upfront payment in the &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;fourth&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;2017&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In December 2021, we earned a $&lt;/span&gt;60&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee payment when Biogen exercised its option to license ION306. &lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We will receive development and regulatory milestone payments from Biogen if new medicines, including ION306, advance towards marketing approval.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $1.2 billion, which is comprised of a $25 million upfront payment, up to $110 million in license fees, up to $80 million in
    development milestone payments, up to $180 million in regulatory milestone payments, up to $800 million in sales milestone payments and other payments, including up to $555
    million if Biogen advances ION306, which includes up to $45 million in development milestone payments, up to $110 million in regulatory milestone payments and up to $400
    million in sales milestone payments. In addition, we are eligible to receive tiered royalties &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;from the mid-teens to &lt;/span&gt;mid-20 percent range &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;on net sales.&lt;/span&gt; From
    inception through December 31, 2022, we received $85 million in payments under this collaboration. We will achieve the next payment of up to $45 million&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for the initiation of a Phase 3 trial under this collaboration. &lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. We determined the transaction price to be the $25 million upfront payment we received when we entered into the collaboration. We allocated the transaction price to our single performance obligation. In the fourth quarter of 2019, we
    completed our R&amp;amp;D services performance obligation under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter of 2021, we identified another performance obligation upon Biogen&#x2019;s license of ION306 because the license we granted
    to Biogen is distinct from our other performance obligations. We recognized the $60 million license fee for ION306 as revenue at that time
    because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is solely responsible for the costs
    and expenses related to the development, manufacturing and potential future commercialization of ION306 following the option exercise. We do not have any remaining performance obligations under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic; font-weight: bold;"&gt;Neurology Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2018 Strategic Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In April 2018, we and Biogen entered into a strategic
      collaboration to develop novel antisense medicines for a broad range of neurological diseases and entered into a Stock Purchase Agreement, or SPA. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to
      develop therapies for these diseases for &lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; years. We are
      responsible for the identification of antisense drug candidates based on selected medicines&lt;/span&gt;. Biogen is responsible for conducting IND-enabling toxicology studies for the selected medicine. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Biogen will have the option to license the selected medicine &lt;/span&gt;after it completes the IND-enabling toxicology study. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;If Biogen exercises its
      option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In the &lt;/span&gt;second&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; quarter of &lt;/span&gt;2018&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we received &lt;/span&gt;$1 billion from Biogen, comprised of $625 million
    to purchase our stock at an approximately 25 percent cash premium and $375 million in an upfront payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of our collaboration, w&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;e are eligible to receive up to $&lt;/span&gt;270&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is comprised of a $&lt;/span&gt;15&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;105&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development milestone payments and up to $&lt;/span&gt;150&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone payments for each medicine that achieves marketing approval. &lt;/span&gt;In addition, we are eligible to receive tiered royalties &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;up to the &lt;/span&gt;20 percent range &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;on net sales.&lt;/span&gt;&#160;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;W&lt;/span&gt;e are currently advancing multiple programs under
    this collaboration and from inception through December 31, 2022, we have received nearly $1.1 billion in payments under this collaboration. We will achieve the next payment of $7.5
    million if Biogen designates or advances another program&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;under this collaboration. &lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;At the commencement of this collaboration, we considered that
      the collaboration agreement and SPA were negotiated concurrently and in contemplation of one another. Based on these facts and circumstances, we concluded that we should evaluate the provisions of the agreements on a combined basis. W&lt;/span&gt;e
    identified one performance obligation, which was to perform R&amp;amp;D services for Biogen.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; We determined our transaction price to be $&lt;/span&gt;552&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, comprised of $&lt;/span&gt;375&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million from the
      upfront payment and $&lt;/span&gt;177&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the premium paid by
      Biogen for its purchase of our common stock.&lt;/span&gt; We determined the fair value of the premium we received by using the stated premium in the SPA and applying a lack of marketability discount. We included a lack of marketability discount in our
    valuation of the premium because Biogen received restricted shares of our common stock. We allocated the transaction price to our single performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From inception through December 31, 2022,
    we have included $616 million &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;in payments in the transaction price
      for our R&amp;amp;D services performance obligation under this collaboration, including $&lt;/span&gt;23&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of milestone payments we achieved in 2021 and $&lt;/span&gt;11&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million of milestone payments we achieved in 2020. These milestone payments did not create new performance obligations because they are part of our original R&amp;amp;D services performance obligation. Therefore, we included
      these amounts in our transaction price for our R&amp;amp;D services performance obligation in the period we achieved the milestone payment. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services based on our
      effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation. We currently estimate we will satisfy our performance obligation at the end of the contractual term in June 2028.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2013 Strategic Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In September 2013, we and Biogen entered into a long-term strategic relationship focused on applying antisense technology to advance the
    treatment of neurodegenerative diseases. As part of the collaboration, Biogen gained exclusive rights to the use of our antisense technology to develop therapies for neurological diseases and has the option to license medicines resulting from this
    collaboration. We will usually be responsible for drug discovery and early development of antisense medicines and Biogen has the option to license antisense medicines after Phase 2 proof-of-concept. In October 2016, we expanded our collaboration to
    include additional research activities we will perform. If Biogen exercises its option to license a medicine, it will assume global development, regulatory and commercialization responsibilities and costs for that medicine. We are currently advancing five investigational medicines in development under this collaboration, including &lt;span style="-sec-ix-hidden:Fact_864d03b225ca4f548971b12e6b3ad3d0"&gt;a&lt;/span&gt; medicine for Parkinson&#x2019;s disease (ION859), two medicines for ALS (tofersen and
    ION541), &lt;span style="-sec-ix-hidden:Fact_7b05dc571fcb46f8bbbe0db51a44d460"&gt;a&lt;/span&gt; medicine for multiple system atrophy (ION464) and &lt;span style="-sec-ix-hidden:Fact_33617a5e2de04e8688f1a06dd038ea29"&gt;a&lt;/span&gt; medicine for an undisclosed target. In the fourth quarter of 2018, Biogen exercised its option to license our most advanced ALS medicine, tofersen, our medicine in registration for SOD1 ALS.
    As a result, Biogen is responsible for global development, regulatory and commercialization activities and costs for tofersen.&lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of the agreement, we received an upfront payment of $100 million and are eligible to receive milestone payments, license fees and royalty payments for all medicines developed under this collaboration, with the specific amounts dependent upon the
    modality of the molecule advanced by Biogen. Under this collaboration, we received a $35 million license fee payment when Biogen licensed
    tofersen from us in 2018.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration for tofersen, we are eligible to receive nearly $110 million, which is comprised of the $35 million license fee received in 2018, up to
    $18 million in development milestone payments and up to $55 million in regulatory milestone payments. For each of the other antisense molecules that are chosen for drug discovery and development under this collaboration, we are eligible to receive up
    to approximately $260 million, which is comprised of a $70 million license fee, up to $60 million in development milestone payments, including
    amounts related to the cost of clinical trials, and up to $130 million in regulatory milestone payments. In addition, we are eligible to receive
    tiered royalties up to the mid-teens on net sales from any antisense medicines developed under this collaboration. From inception through December 31, 2022,
    we have received more than $300 million in payments under this collaboration. We will achieve the next payment of $16 million if the FDA approves Biogen&#x2019;s NDA filing of tofersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of our 2013 strategic neurology collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Biogen. At inception, we determined the transaction price to be the $100 million upfront payment we received and allocated it to our single performance obligation. As we achieve milestone payments for our R&amp;amp;D services, we include these amounts in our
    transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our
    performance obligation&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;During 2020, we completed our remaining&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; research and development
      services and recognized the remaining revenue related to this performance obligation. &lt;/span&gt;From inception through the completion of our R&amp;amp;D services performance obligation in 2020, we included $145 million in total payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under this collaboration, we have also generated additional
      payments that we concluded were not part of our R&amp;amp;D services performance obligation. We recognized each of these payments in full in the respective quarter we generated the payment because we did not have any performance obligations for the
      respective payment. For example, in the third quarter of 2022, we earned a &lt;/span&gt;$9&#160;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;million milestone payment when the FDA accepted Biogen&#x2019;s NDA filing of tofersen, which we recognized in full because we did not have any performance obligations related to this milestone payment.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;2012 Neurology&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 35.3pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2012, we and Biogen entered into a collaboration agreement to develop and commercialize novel antisense medicines to treat
    neurodegenerative diseases. We are responsible for the development of each of the medicines through the completion of the initial Phase 2 clinical study for such medicine. Biogen has the option to license a medicine from each of the programs through
    the completion of the first Phase 2 study for each program. Under this collaboration, Biogen is conducting the IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; study for AD and we are currently advancing ION582 for AS. If Biogen exercises its option to license a medicine, it
    will assume global development, regulatory and commercialization responsibilities and costs for that medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Under the terms of the agreement, we received an upfront
      payment of $&lt;/span&gt;30&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. Over the term of the collaboration,
      we are eligible to receive up to $&lt;/span&gt;210&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is
      comprised of a $&lt;/span&gt;70&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development milestone payments per program and up to $&lt;/span&gt;130&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestone payments per program, plus a mark-up on the
      cost estimate of the Phase 1 and 2 studies. In addition, we are eligible to receive tiered royalties up to the mid-teens on net sales of any medicines resulting from each of the &lt;/span&gt;two&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; programs. From inception through &lt;/span&gt;December 31, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received nearly $&lt;/span&gt;170&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration, including nearly $&lt;/span&gt;20&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in milestone payments we received from Biogen for advancing ION582 and a $&lt;/span&gt;10&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone payment we received from Biogen when Biogen advanced &lt;/span&gt;IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;&lt;sub&gt;&#160;&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;during 2022. We will achieve the next payment of up to $&lt;/span&gt;25&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;million if Biogen advances a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under our collaboration, we determined we had a performance obligation to perform R&amp;amp;D services. We allocated $40 million in total payments to the transaction price for our R&amp;amp;D services performance obligation. In the third quarter of 2019, we completed our
    R&amp;amp;D services performance obligation when we designated a development candidate and Biogen accepted the development candidate. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the
    total effort expected to satisfy our performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;When we commenced development for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; we identified our development work as a separate performance obligation. In the
    fourth quarter of 2022, we completed our R&amp;amp;D services performance obligation for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;. We recognized revenue as we performed services based on our effort to satisfy our performance obligation relative to the total effort expected
    to satisfy our performance obligation. From inception through December 31, 2022, we have included $57 million in the transaction price for our IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; development performance obligation, including $19.5 million of milestone payments we earned from Biogen in 2020 when we advanced IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter of 2019, we identified another performance obligation upon Biogen&#x2019;s license of IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt; because the
    license we granted to Biogen is distinct from our other performance obligations. We recognized the $45 million license fee for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;
    as revenue at that time because Biogen had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Biogen. Biogen is
    responsible for global development, regulatory and commercialization activities and costs for IONIS-MAPT&lt;sub&gt;Rx&lt;/sub&gt;.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter of 2022, we &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;achieved $&lt;/span&gt;14.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in milestone payments when Biogen advanced ION582. &lt;/span&gt;We will
    recognize revenue as we perform services based on our effort to satisfy our R&amp;amp;D services performance obligation relative to the total effort expected to satisfy our performance obligation&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for ION582.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;242.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;267.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;428.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;408.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheets at December 31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;351.2&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;407.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, respectively, related to our relationship with Biogen.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Joint Development and Commercialization Arrangement&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Eplontersen Collaboration&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2021, we entered into a joint development and commercialization agreement with AstraZeneca to develop and commercialize
    eplontersen for the treatment of ATTR. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. We granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S., except certain countries in
    Latin America.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $3.6 billion, which is comprised of a $200 million upfront payment, up to $485 million in development and approval milestone payments and up to $2.9 billion in sales milestone payments. The agreement also includes territory-specific development, commercial and medical affairs cost-sharing provisions. In addition, we are eligible to
    receive up to mid-20 percent royalties for sales in the U.S. and tiered royalties up to the high teens for sales outside the U.S.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We evaluated our eplontersen collaboration under ASC 808 and identified four material components: (i) the license we granted to AstraZeneca in 2021, (ii) the co-development activities that we and AstraZeneca will perform, (iii) the co-commercialization activities
    that we and AstraZeneca will perform and (iv) the co-medical affairs activities that we and AstraZeneca will perform.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that we had a vendor-customer relationship within the scope of ASC 606 for the license we granted to AstraZeneca and as a
    result we had one performance obligation. For our sole performance obligation, we determined the transaction price was the $200 million upfront payment we received. We recognized the upfront payment in full in 2021 because we did not have any remaining performance obligations
    after we delivered the license to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We also concluded that the co-development activities, the co-commercialization activities and the co-medical affairs activities are within
    the scope of ASC 808 because we and AstraZeneca are active participants exposed to the risks and benefits of the activities under the collaboration. AstraZeneca is currently responsible for 55 percent of the costs associated with the ongoing global Phase 3 development program. Because we are leading the Phase 3 development program, we recognize as revenue the 55 percent of cost-share funding AstraZeneca is responsible for in the same period we incur the related development expenses. As AstraZeneca is responsible
    for the majority of the commercial and medical affairs costs in the U.S. and all costs associated with bringing eplontersen to market outside the U.S., we recognize cost-share funding we receive from AstraZeneca related to these activities as a
    reduction of our commercial and medical affairs expenses.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We will achieve the next payment of up to $50
    million upon the first regulatory approval under this collaboration. From inception through December 31, 2022, we have received nearly $260 million in payments under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Research and Development Partners&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;AstraZeneca&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In addition to our collaboration for eplontersen, we have a collaboration with AstraZeneca focused on the treatment of cardiovascular,
    renal and metabolic diseases. In July 2015, we and AstraZeneca formed a collaboration to discover and develop antisense therapies for treating cardiovascular, renal and metabolic diseases. Under our collaboration, AstraZeneca has licensed multiple
    medicines from us, including medicines in development to treat people with ATTR amyloidosis, a genetically associated form of kidney disease and &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;NASH&lt;/span&gt;. AstraZeneca is
    responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $5.8 billion, which is comprised of a $65 million upfront payment, up to $290 million in license fees, up to $1.1 billion
    in development milestone payments, up to $2.9 billion in regulatory milestone payments and up to $1.5 billion in sales milestone payments. In addition, we are eligible to receive tiered royalties up to the low teens on net sales from any product that AstraZeneca successfully
    commercializes under this collaboration agreement. We will achieve the next payment of $10 million under this collaboration if AstraZeneca
    advances a medicine under this collaboration&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt; From inception through December 31, 2022, we have received more than $280 million in payments under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for AstraZeneca. We determined the transaction price to be the $65 million upfront payment we received and we allocated it to our single performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation as we performed services
    based on our effort to satisfy this performance obligation relative to our total effort expected to satisfy our performance obligation. We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; completed our performance obligation
      in&lt;/span&gt; the fourth quarter of 2021. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our transaction price for our R&amp;amp;D services performance obligation. From inception through the completion of our
    performance obligation, we have included $90 million in payments in the transaction price for our R&amp;amp;D services performance obligation.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. For example, in the fourth
    quarter of 2021, we earned a $30 million license fee when AstraZeneca licensed a target for a metabolic disease. We recognized the license fee as
    revenue at that time because AstraZeneca had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to AstraZeneca.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;254.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with AstraZeneca at December 31, 2022 and 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;GSK&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In March 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines
    against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK currently includes two medicines targeting hepatitis B virus, or HBV: bepirovirsen and IONIS-HBV-L&lt;sub&gt;Rx&lt;/sub&gt;. We designed these medicines to reduce the production of viral proteins associated with HBV
    infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive nearly $260 million, which is comprised of a $25 million license fee, up to $42.5 million in development milestone payments, up to $120
    million in regulatory milestone payments and up to $70 million in sales milestone payments if GSK successfully develops bepirovirsen. In
    addition, we are eligible to receive tiered royalties up to the low-teens on net sales of bepirovirsen. From inception through December 31, 2022,
    we have received more than $50 million in payments under the HBV program collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We completed our R&amp;amp;D services performance obligations
      under our collaboration in the first quarter of 2015. &lt;/span&gt;We identified a new performance obligation when we granted GSK the license of the HBV program and assigned related intellectual property rights in the third quarter of 2019 because the
    license was distinct from our other performance obligations. We recognized the $25 million license fee for the HBV program as revenue at that
    time because GSK had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to GSK.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We do not have any remaining performance obligations under our collaboration with GSK; however, we can still earn additional payments and
    royalties as GSK advances the HBV program.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; In January 2023, we earned a $&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million milestone when GSK initiated a Phase 3 study of bepirovirsen. We will achieve the next payment of $&lt;/span&gt;15&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if the FDA accepts an NDA filing of bepirovirsen for review.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with GSK at December 31, 2022 and 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Novartis&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In January 2017, we initiated a collaboration with Novartis
      to develop and commercialize pelacarsen and olezarsen.&lt;/span&gt; Novartis is responsible for conducting and funding development and regulatory activities for pelacarsen, including a global Phase 3 cardiovascular outcomes study that Novartis initiated in
    the fourth quarter 2019.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;In connection with Novartis&#x2019; license of pelacarsen, we and Novartis established a more definitive framework under which the companies would
    negotiate the co-commercialization of pelacarsen in selected markets. Included in this framework is an option by which Novartis could solely commercialize pelacarsen in exchange for Novartis paying us increased sales milestone payments based on sales
    of pelacarsen.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;When Novartis decided to not exercise its option for &lt;/span&gt;olezarsen, we retained rights to develop and commercialize olezarsen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $900 million, which is comprised of a $75 million upfront payment, a $150 million license fee, a $25 million
    development milestone payment, up to $290 million in regulatory milestone payments and up to $360 million in sales milestone payments. &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;From inception through &lt;/span&gt;December 31, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, we have received nearly $&lt;/span&gt;275&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in payments under this collaboration. &lt;/span&gt;We are also eligible to receive tiered royalties in the
    mid-teens to low 20 percent range on net sales of pelacarsen. In August 2021, we earned a $25 million milestone payment from Novartis when Novartis achieved 50 percent
    enrollment in the Lp(a) HORIZON Phase 3 cardiovascular outcome study of pelacarsen. We recognized the milestone payment in full in the third quarter of 2021 because we did not have any remaining performance obligations related to the milestone payment.
    &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; will achieve the next payment of up to $&lt;/span&gt;75&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if Novartis advances regulatory
      activities for pelacarsen.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In conjunction with this collaboration, we entered into a SPA with Novartis. As part of the SPA, Novartis purchased 1.6 million shares of our common stock for $100
    million in the first quarter of 2017.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified four separate performance obligations:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D services for pelacarsen;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D services for olezarsen;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;API for pelacarsen; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;API for olezarsen.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined that the R&amp;amp;D services for each medicine and the API for each medicine were distinct performance obligations.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We determined our transaction price to be $108.4
    million, comprised of the following:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$75 million from the upfront payment;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$28.4 million for the premium paid by Novartis for its purchase
            of our common stock at a premium in the first quarter of 2017; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$5.0 million for the potential premium Novartis would have paid
            if they purchased our common stock in the future.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We allocated the transaction price based on the estimated stand-alone selling price of each performance obligation as follows:&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$&lt;/span&gt;64.0&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million for the R&amp;amp;D services for pelacarsen;&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$40.1 million for the R&amp;amp;D services for &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;olezarsen&lt;/span&gt;; &lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$1.5&lt;/span&gt;
            million for the delivery of pelacarsen API; and&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 36pt;"/&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x25cf;&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;$2.8&lt;/span&gt;
            million for the delivery of olezarsen API.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We completed our R&amp;amp;D services performance obligations for olezarsen and pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;in 2019. As such, we recognized all
    revenue we allocated to the olezarsen and pelacarsen&lt;sub&gt;&#160;&lt;/sub&gt;R&amp;amp;D services as of the end of 2019.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We recognized revenue related to the R&amp;amp;D services for
      pelacarsen and olezarsen performance obligations as we performed services &lt;/span&gt;based on our effort to satisfy our performance obligations relative to our total effort expected to satisfy our performance obligations&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.5&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with Novartis at December 31, 2022 and 2021.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As described in the &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Biogen SPINRAZA&lt;/span&gt;
    section above, in January 2023, we entered into a royalty purchase agreement with Royalty Pharma. Under the agreement, in addition to a minority interest in SPINRAZA royalties, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen. Refer to Part IV, Item 15, Note 4, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Long-Term Obligations and Commitments&lt;/span&gt;, for further discussion of this agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Roche&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; margin-left: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Huntington&#x2019;s Disease&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In April 2013, we formed an alliance with Hoffmann-La Roche Inc and F. Hoffmann-La Roche Ltd, collectively Roche, to develop treatments
      for HD based on our antisense technology. Under the agreement, we discovered and developed tominersen, an investigational medicine targeting HTT protein. We developed tominersen through completion of our Phase 1/2 clinical study in people with
      early-stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for
      tominersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Over the term of the collaboration, we are eligible to receive up to $395 million, which is comprised of a $30 million upfront payment, a $45 million license fee, up to $70 million in
    development milestone payments, up to $170 million in regulatory milestone payments and up to $80 million in sales milestone payments as tominersen advances. In addition, we are eligible to receive up to $136.5 million in milestone payments for each additional medicine successfully developed. We are also eligible to receive tiered royalties up to the mid-teens on net sales of any product
    resulting from this alliance. From inception through December 31, 2022, we have received more than $150 million in payments under this collaboration. We will achieve the next payment of $17.5
    million if Roche advances a medicine under this collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $30 million upfront payment we received and allocated it to our single performance obligation. As we achieved milestone payments for our R&amp;amp;D services, we included these amounts in our
    transaction price for our R&amp;amp;D services performance obligation. We recognized revenue for our R&amp;amp;D services performance obligation over our period of performance, which ended in the third quarter of 2017.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under this collaboration, we have also generated additional payments that we concluded were not part of our R&amp;amp;D services performance
    obligation. We recognized each of these payments in full in the respective quarter in which we generated the payment because the payments were distinct and we did not have any performance obligations for the respective payment. In 2019, we earned $35 million in milestone payments when Roche advanced tominersen under this collaboration. In March 2021, Roche decided to discontinue dosing in the Phase 3
    GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In January 2023, Roche initiated the Phase 2, GENERATION HD2, study of tominersen in patients with prodromal or early manifest HD. Roche
    is focusing on early-stage and younger patients based on the post-hoc analyses from the GENERATION HD1 study that suggested tominersen may benefit these patient groups. We do not have any remaining performance obligations related to tominersen under
    this collaboration with Roche; however, we can still earn additional payments and royalties as Roche advances tominersen.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: left; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;IONIS-FB-L&lt;/span&gt;&lt;sub&gt;&lt;span style="background-color: #FBFBFB;"&gt;Rx&lt;/span&gt;&lt;/sub&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; for Complement-Mediated Diseases&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In October 2018, we entered into a collaboration agreement with Roche to&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; develop IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt; for the treatment of complement-mediated diseases. We are currently conducting Phase 2 studies in two disease indications for &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;, one for the treatment of patients with GA, the advanced stage of dry AMD, and a &lt;span style="-sec-ix-hidden:Fact_04500eaf787641bfbd86183ba9891b89"&gt;second&lt;/span&gt; for the treatment of patients with IgA nephropathy.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;After positive data from a Phase 2 clinical study, &lt;/span&gt;Roche&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; licensed IONIS-FB-L&lt;/span&gt;&lt;sub&gt;&lt;span style="background-color: #FBFBFB;"&gt;Rx&lt;/span&gt;&lt;/sub&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; in &lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;July 2022&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;for $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. As a result, Roche is responsible for global development, regulatory and commercialization activities, and costs for IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, except for the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA, both of which we are conducting and funding. In July 2022, we amended our IONIS-FB-L&lt;/span&gt;&lt;sub&gt;Rx&lt;/sub&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that
      would require adjustments to revenue we previously recognized.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Over the term of the collaboration, we are eligible to
      receive more than $&lt;/span&gt;810&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million, which is comprised of a $&lt;/span&gt;75&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million upfront payment, a $&lt;/span&gt;35&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million license fee, up to $&lt;/span&gt;145&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in development milestones, up to $&lt;/span&gt;279&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in regulatory milestones and up to $&lt;/span&gt;280&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million in sales milestone payments. In addition, we are also eligible to receive tiered royalties from the high
      teens to &lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; on net sales.&lt;/span&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;From inception through December 31, 2022,
    we have received more than $130 million in payments under this collaboration. &lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We will achieve the next payment of up to $&lt;/span&gt;90&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million if Roche advances IONIS-FB-L&lt;/span&gt;&lt;sub&gt;&lt;span style="background-color: #FBFBFB;"&gt;Rx&lt;/span&gt;&lt;/sub&gt;&lt;span style="background-color: #FBFBFB; font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; under this collaboration.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;At the commencement of this collaboration, we identified one performance obligation, which was to perform R&amp;amp;D services for Roche. We determined the transaction price to be the $75 million upfront payment we received and allocated it to our single performance obligation. We are recognizing revenue for our R&amp;amp;D services performance obligation as we perform services
    based on our effort to satisfy our performance obligation relative to our total effort expected to satisfy our performance obligation.&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;&#160;&lt;/span&gt;We&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; currently estimate we will satisfy our performance obligation in &lt;/span&gt;the third quarter of 2024.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;Our &lt;/span&gt;consolidated balance sheets at December 31&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, &lt;/span&gt;2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; and &lt;/span&gt;2021&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; included deferred
      revenue of $&lt;/span&gt;22.4&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million and $&lt;/span&gt;31.6&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million related to our relationship with Roche, respectively.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Commercialization Partnerships&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Swedish Orphan Biovitrum AB (Sobi)&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We began commercializing TEGSEDI and WAYLIVRA in Europe in January 2021 and TEGSEDI in North America in April 2021 through distribution
    agreements with Sobi. Under our agreements, we are responsible for supplying finished goods inventory to Sobi and Sobi is responsible for selling each medicine to the end customer. In exchange, we earn a distribution fee on net sales from Sobi for each
    medicine.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;PTC Therapeutics&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;In August 2018, we entered into an exclusive license
      agreement with PTC Therapeutics to commercialize TEGSEDI and WAYLIVRA in Latin America and certain Caribbean countries. Under the license agreement, we are eligible to receive royalties from PTC in the mid-&lt;/span&gt;20 percent&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; range on net sales for each medicine. &lt;/span&gt;In December 2021, we started receiving
    royalties from PTC for TEGSEDI sales&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Technology Enhancement Collaborations&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Bicycle License Agreement&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In December 2020, we entered into a collaboration agreement with Bicycle and obtained an option to license its peptide technology to
    potentially increase the delivery capabilities of our LICA medicines. In July 2021, we paid $42 million when we exercised our option to license
    Bicycle&#x2019;s technology, which included an equity investment in Bicycle. As part of our stock purchase, we entered into a lockup agreement with Bicycle that restricted our ability to trade our Bicycle shares for one year. In 2021, we recorded a $7.2 million equity investment for the
    shares we received in Bicycle. We recognized the remaining $34.8 million as R&amp;amp;D expense in 2021. From inception through December 31, 2022, we have paid Bicycle $46.6
    million under this collaboration agreement.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Metagenomi License Agreement&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In November 2022, we entered into a collaboration and license agreement with Metagenomi to research, develop and commercialize
    investigational medicines for up to four initial genetic targets, and, upon the achievement of certain development milestones, four additional genetic targets using gene editing technologies. As a result, we paid $80 million to license Metagenomi&#x2019;s technologies. We recorded the $80 million payment as
    R&amp;amp;D expense in 2022 upon receiving a license from Metagenomi for intellectual property that is in research with no current alternate use. We will also pay Metagenomi certain fees for the selection of genetic targets, and contingent on the
    achievement of certain development, regulatory and sales events, milestone payments and royalties. In addition, we will reimburse Metagenomi for certain of its costs in conducting its research and drug discovery activities under the collaboration.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Other Agreements&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-style: italic;"&gt;Alnylam Pharmaceuticals, Inc.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Under the terms of our agreement with Alnylam, we co-exclusively (with ourselves) licensed to Alnylam our patent estate relating to
      antisense motifs and mechanisms and oligonucleotide chemistry for double-stranded RNAi therapeutics, with Alnylam having the exclusive right to grant platform sublicenses for double-stranded RNAi. In exchange for such rights, Alnylam gave us a
      technology access fee, participation in fees from Alnylam&#x2019;s partnering programs, as well as future milestone and royalty payments from Alnylam. We retained exclusive rights to our patents for single-stranded antisense therapeutics and for a limited
      number of double-stranded RNAi therapeutic targets and all rights to single-stranded RNAi, or ssRNAi, therapeutics. In turn, Alnylam nonexclusively licensed to us its patent estate relating to antisense motifs and mechanisms and oligonucleotide
      chemistry to research, develop and commercialize single-stranded antisense therapeutics, ssRNAi therapeutics, and to research double-stranded RNAi compounds. We also received a license to develop and commercialize double-stranded RNAi therapeutics
      targeting a limited number of therapeutic targets on a nonexclusive basis. Additionally, in 2015, we and Alnylam entered into an alliance in which we cross-licensed intellectual property. Under this alliance, we and Alnylam each obtained exclusive
      license rights to 4 therapeutic programs. Alnylam granted us an exclusive, royalty-bearing license to its chemistry, RNA targeting mechanism
      and target-specific intellectual property for oligonucleotides against four targets, including FXI and Apo(a) and two other targets. In exchange, we granted Alnylam an exclusive, royalty-bearing license to our chemistry, RNA targeting mechanism and target-specific
      intellectual property for oligonucleotides against four other targets. Alnylam also granted us a royalty-bearing, non-exclusive license to new
      platform technology arising from May 2014 through April 2019 for single-stranded antisense therapeutics. In turn, we granted Alnylam a royalty-bearing, non-exclusive license to new platform technology arising from May 2014 through April 2019 for
      double-stranded RNAi therapeutics.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;In the fourth quarter 2020, we completed an arbitration process with Alnylam. The arbitration panel awarded us $41.2 million for payments owed to us by Alnylam related to Alnylam&#x2019;s agreement with Sanofi Genzyme. We recognized the $41.2 million payment from Alnylam as revenue in the fourth quarter of 2020 because we did not have any performance obligations for the respective payment.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Alnylam (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 12pt;"&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We did not have any
    deferred revenue from our relationship with Alnylam at December 31, 2022 and 2021.&lt;/div&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

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  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;SPINRAZA royalties (commercial revenue)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;242.3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;267.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;286.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;124.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;161.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;122.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Total revenue from our relationship with Biogen&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;366.7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;428.8&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;408.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;62&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;53&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;56&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with AstraZeneca (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;79.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;254.6&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;88.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;13&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;31&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;12&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with GSK (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Novartis (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

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          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;0.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;25.5&lt;/div&gt;
        &lt;/td&gt;

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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.0&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;3&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

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    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

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          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;67.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;17.2&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;5.9&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;11&lt;/div&gt;
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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;2&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
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      contextRef="c20150101to20151231_TypeOfArrangementAxis_AlnylamCollaborationMember"
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    <us-gaap:LitigationSettlementAmountAwardedFromOtherParty
      contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember"
      decimals="-5"
      id="Fact_dfb16bacc6b94e7989aea7d88eebed5b"
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      contextRef="c20201001to20201231_TypeOfArrangementAxis_AlnylamCollaborationMember"
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      id="Fact_397eed8f6b004e30bfacdacc310446cf"
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    <us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock
      contextRef="c20220101to20221231_TypeOfArrangementAxis_AlnylamPharmaceuticalsIncMember"
      id="Text_0f88f578e1cc4bc5928904be72a89aac">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;During the years ended December 31, 2022, 2021 and 2020, we earned the following revenue from our relationship with Alnylam (in millions, except percentage amounts):&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
    &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;

        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="10" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Year Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2020&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -27pt; margin-left: 27pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;R&amp;amp;D revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;21.4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;47.9&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Percentage of total revenue&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;4&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;7&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;%&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:SchedulesOfConcentrationOfRiskByRiskFactorTextBlock>
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      contextRef="c20220101to20221231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_AlnylamCollaborationMember"
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      id="Fact_45285d7fd8354da4a078a4a11aba04ee"
      unitRef="U001">21400000</us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax>
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      contextRef="c20210101to20211231_ProductOrServiceAxis_ResearchAndDevelopmentRevenueMember_TypeOfArrangementAxis_AlnylamCollaborationMember"
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&lt;div style="text-align: justify; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;8. Employment Benefits&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of
    their salary up to the IRS annual limits of $20,500 and $27,000 in 2022 for employees under 50 years old and employees 50 years old or over,
    respectively. We made approximately $5.6 million, $5.5
    million and $5.7 million in matching contributions for the years ended December 31, 2022, 2021 and 2020, respectively.&lt;/div&gt;
</us-gaap:PensionAndOtherPostretirementBenefitsDisclosureTextBlock>
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      contextRef="c20220101to20221231_RangeAxis_MaximumMember"
      decimals="0"
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      id="Fact_345fd7748408424580894d7cb0e0e108"
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    <us-gaap:LegalMattersAndContingenciesTextBlock
      contextRef="c20220101to20221231"
      id="Text_656730b2a28e4e958b751e639ff66fd5">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;9. Legal Proceedings&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the
    status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of
    any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the
    amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates.&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On August 5, 2021, &lt;/span&gt;four&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; purported former stockholders of Akcea filed an action in the Delaware
      Court of Chancery captioned John Makris, et al. v. Ionis Pharmaceuticals, Inc., et al., C.A. No. 2021-0681, or the Delaware Action. The plaintiffs in the Delaware Action asserted claims against (i) former members of Akcea&#x2019;s board of directors; and
      (ii) Ionis, or collectively, the Defendants. The plaintiffs asserted putatively direct claims on behalf of a purported class of former Akcea stockholders. The plaintiffs in the Delaware Action asserted that the Defendants breached their fiduciary
      duties in connection with the October 2020 take-private transaction that Ionis and Akcea entered into, in which Akcea became a wholly-owned subsidiary of Ionis. We believe this lawsuit is without merit. However, the outcome of this lawsuit or any
      other lawsuit that may be filed challenging the October 2020 take-private transaction is uncertain. Accordingly, on June 3, 2022, the parties reached an agreement in principle to settle the Delaware Action for $&lt;/span&gt;12.5&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million. A Stipulation and Agreement of Compromise, Settlement and
      Release, or the Stipulation and Settlement Agreement reflecting the terms of the proposed settlement was executed and filed with the Delaware Court of Chancery on July 5, 2022. On October 11, 2022, the Delaware Court of Chancery entered an Order and
      Final Judgment, or the Order, approving the Stipulation and Settlement Agreement in full after determining that the Stipulation and Settlement Agreement was fair, reasonable, and adequate. The Order provides for the full settlement, satisfaction,
      compromise and release of all claims that were asserted in the Delaware Action. The Order contains no admission of wrongdoing on the part of any of the Defendants. We recorded a net settlement expense of $&lt;/span&gt;7.7&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt; million within other expense in the accompanying consolidated statements of operations in 2022.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;January 19, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. &lt;/span&gt;No&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;2022-0059&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or the Shumacher Action. The complaint names Ionis&#x2019; board of directors, or the
      Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also
      asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys&#x2019; fees and costs, and such other relief as deemed just and
      proper by the court. On &lt;/span&gt;March 18, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Ionis and the Board moved to dismiss the complaint. On May 24, 2022, the parties entered into a Stipulation and Agreement of
      Compromise, Settlement and Release.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;May 25, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. &lt;/span&gt;No&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. &lt;/span&gt;2022-0453&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, or the Cohen Action. The complaint names the Board as defendants and names Ionis
      as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive
      non-executive director compensation for the years &lt;/span&gt;2018, 2019&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, and &lt;/span&gt;2020&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;. On &lt;/span&gt;June
    2, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On &lt;/span&gt;July 5, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action.&lt;/span&gt;&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;On &lt;/span&gt;July 18, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, Ionis filed a Form &lt;/span&gt;8&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of
      Action. On &lt;/span&gt;September 21, 2022&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action
      plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. On February 7, 2023, the parties entered into
      an Amended Stipulation and Agreement of Compromise, Settlement and Release. We and our Board have denied, and continue to deny, any and all allegations of wrongdoing or liability asserted in the Shumacher and Cohen Actions.&lt;/span&gt;&lt;/div&gt;
</us-gaap:LegalMattersAndContingenciesTextBlock>
    <us-gaap:LossContingencyNumberOfPlaintiffs
      contextRef="c20210805to20210805_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember"
      decimals="INF"
      id="Fact_6cdf774705754659a263bf5c8a541dec"
      unitRef="U023">4</us-gaap:LossContingencyNumberOfPlaintiffs>
    <us-gaap:LitigationSettlementAmountAwardedToOtherParty
      contextRef="c20220603to20220603_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember"
      decimals="-5"
      id="Fact_eb4ae031e3ba4e1e97657c914f4147c7"
      unitRef="U001">12500000</us-gaap:LitigationSettlementAmountAwardedToOtherParty>
    <us-gaap:GainLossRelatedToLitigationSettlement
      contextRef="c20220101to20221231_IncomeStatementLocationAxis_OtherNonoperatingIncomeExpenseMember_LitigationCaseAxis_JohnMakrisEtAlVIonisPharmaceuticalsIncEtAlMember"
      decimals="-5"
      id="Fact_1cde3f8ecdf246ce9c8274576d01faf4"
      unitRef="U001">7700000</us-gaap:GainLossRelatedToLitigationSettlement>
    <us-gaap:QuarterlyFinancialInformationTextBlock
      contextRef="c20220101to20221231"
      id="Text_4be6328593df49c295c60f8f5c9d4bc0">
&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;10. Fourth Quarter Financial Data (Unaudited)&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following financial information reflects all normal recurring adjustments, which are, in the opinion
    of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2022 and 2021 are as follows (in thousands, except per share data).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;151,890&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;440,006&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;359,909&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;219,403&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(208,019&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220,603&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income (loss) (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52,430&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,613&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income (loss) per share (4) (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Diluted net income (loss) per share (4) (6)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.41&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $80 million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net income (loss) per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;141,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;0 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;777&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,936&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;0.125 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;1 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;226,210&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160,340&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.41&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;
</us-gaap:QuarterlyFinancialInformationTextBlock>
    <us-gaap:ScheduleOfQuarterlyFinancialInformationTableTextBlock
      contextRef="c20220101to20221231"
      id="Text_53a7dc3cb94e432bbe1ab7ec6da16d34">
&lt;div style="display:none;"&gt;&lt;br/&gt;&lt;/div&gt;
&lt;div style="text-align: justify; text-indent: 36pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;The following financial information reflects all normal recurring adjustments, which are, in the opinion
    of management, necessary for a fair statement of the results of the interim periods. Summarized fourth quarter data for 2022 and 2021 are as follows (in thousands, except per share data).&lt;/div&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31,&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2022&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue (1)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;151,890&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;440,006&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses (2)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;359,909&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;219,403&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income (loss) from operations&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(208,019&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;220,603&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income (loss) (3)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(52,430&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,613&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Basic net income (loss) per share (4) (5)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; width: 76%;" valign="bottom"&gt;
          &lt;div style="text-align: justify; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Diluted net income (loss) per share (4) (6)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(0.37&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.41&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;________________&lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(1)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Revenue was lower in the three months ended
            December 31, 2022 compared to the same period in 2021 due to the $200 million we earned in the fourth quarter of 2021 from AstraZeneca to
            jointly develop and commercialize eplontersen.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(2)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Operating expenses were higher in the three
            months ended December 31, 2022 compared to the same period in 2021 primarily due to the $80 million upfront payment we made for our
            collaboration with Metagenomi in the fourth quarter of 2022.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(3)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Our net loss for the three months ended
            December 31, 2022 includes the $150.1 million gain we recognized from the sale and leaseback transaction for our headquarters in
            Carlsbad, California.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(4)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;We &lt;/span&gt;compute net income (loss) per share independently for each quarter during &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif;"&gt;the year.&lt;/span&gt;&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(5)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;As discussed in Note 1, &lt;span style="font-size: 10pt; font-family: 'Times New Roman', Times, serif; font-style: italic;"&gt;Organization and Significant Accounting Policies, &lt;/span&gt;we compute basic net income (loss) per share by dividing the total net income (loss) by our
            weighted-average number of common shares outstanding during the period.&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="DSPFListTable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; width: 100%; text-align: left; color: #000000;"&gt;


  &lt;tr&gt;

    &lt;td style="width: 18pt; vertical-align: top; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;(6)&lt;/td&gt;

    &lt;td style="width: auto; vertical-align: top; text-align: justify;"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;We had net income for the fourth quarter of
            2021. As a result, we computed diluted net income per share using the weighted-average number of common shares and dilutive common equivalent shares outstanding during the period as follows (in thousands except per share amounts):&lt;/div&gt;
        &lt;/td&gt;

  &lt;/tr&gt;


&lt;/table&gt;

&lt;div&gt;&lt;br/&gt;
  &lt;/div&gt;

&lt;table cellpadding="0" cellspacing="0" class="cfttable" style="font-family: 'Times New Roman', Times, serif; font-size: 10pt; text-align: left; color: #000000; width: 100%;"&gt;


  &lt;tr&gt;

    &lt;td style="vertical-align: bottom; border-bottom: #000000 2px solid;" valign="bottom"&gt;
          &lt;div style="text-align: left; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Three Months Ended December 31, 2021&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Income&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Numerator)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Shares&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;(Denominator)&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="2" style="vertical-align: bottom; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Per-Share&lt;/div&gt;
          &lt;div style="text-align: center; font-family: 'Times New Roman', Times, serif; font-size: 10pt; font-weight: bold;"&gt;Amount&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Net income available to Ionis common stockholders&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;224,612&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;141,205&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1.59&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 9pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Effect of dilutive securities:&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon exercise of stock options&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;46&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable upon restricted stock award issuance&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;1,065&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our ESPP&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;&#x2014;&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;34&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;0 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;777&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;10,936&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;0.125 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;716&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;6,590&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 2px;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9pt; margin-left: 21pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Shares issuable related to our &lt;span style="text-indent: 0pt;"&gt;1 percent&lt;/span&gt; convertible notes&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;105&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;464&lt;/div&gt;
        &lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 solid 2px;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 2px; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;

  &lt;tr&gt;

    &lt;td style="vertical-align: top; width: 64%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="text-align: left; text-indent: -9.1pt; margin-left: 9.1pt; font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;Income available to Ionis common stockholders, plus assumed conversions&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

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          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;160,340&lt;/div&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF;" valign="bottom"&gt;&#160;&lt;/td&gt;

    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
          &lt;div style="font-family: 'Times New Roman', Times, serif; font-size: 10pt;"&gt;$&lt;/div&gt;
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    &lt;td colspan="1" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: #000000 double 4px; background-color: #CCEEFF;" valign="bottom"&gt;
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    &lt;td colspan="1" style="text-align: left; vertical-align: bottom; width: 1%; padding-bottom: 4px; background-color: #CCEEFF; white-space: nowrap;" valign="bottom"&gt;&#160;&lt;/td&gt;

  &lt;/tr&gt;


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end
</TEXT>
</DOCUMENT>
</SEC-DOCUMENT>
